Download SPINRAZA READINESS KIT

SPINRAZA
READINESS KIT
Please see full Prescribing Information for important safety information.
MANAGEMENT OF THE REIMBURSEMENT PROCESS FOR SPINRAZA
1
SELECT TREATMENT
AFTER DISCUSSING
BENEFITS AND RISKS
2
CONDUCT A BENEFIT
INVESTIGATION
Tip: Thoroughly investigate specific
payer requirements regarding
• Coverage and documentation
• Product acquisition
• Patient cost sharing
• Site of care
• Coding and billing
4
IS A PRIOR
AUTHORIZATION
AND/OR MEDICAL
EXCEPTION
REQUIRED?
YES
3
SCHEDULE PATIENT TREATMENT
AND ORDER SPINRAZA
Tip: Submit the SPINRAZA Start
Form to enroll your patient in Biogen
support services.
Review plan requirements for a prior authorization,
complete form, and submit
OR
Submit a medical exception request using a letter of
medical necessity and supporting documentation
NO
5
SUBMIT THE CLAIM
6
TRACK REIMBURSEMENT
Tip: Establish an efficient claim
submission process that includes
Tip: Ensure appropriate
payment by
• Appropriate documentation
• Accurate coding
• Timely submissions
• Monitoring payer
remittance
• Appealing, if necessary
For more information on how to submit
claims and track reimbursement, please see
the Guide to SPINRAZA Reimbursement or
ask your Biogen representative
If the plan denies the prior authorization or medical exception request, you can appeal and resubmit the request.
Please see full Prescribing Information for important safety information.
2
SPINRAZA™ (nusinersen) READINESS KIT RESOURCES
SPINRAZA READINESS KIT WELCOME LETTER
The welcome letter provides an overview of the kit and a summary of included items.
SPINRAZA PRODUCT FACT SHEET
This fact sheet provides information about SPINRAZA. In addition, this sheet also includes the relevant product
and procedure codes for SPINRAZA.
SPINRAZA FREQUENTLY ASKED QUESTIONS
This resource includes the answers to questions that your office or facility may have about SPINRAZA.
SPINRAZA CLINICAL OVERVIEW
This overview provides information about the multiple clinical studies with SPINRAZA, including the trial
designs and efficacy and safety results.
TIPS TO SUCCESSFULLY COMPLETING THE SPINRAZA START FORM
This guide explains the SPINRAZA Start Form and provides tips on how to complete each section so that
your patients can enroll in Biogen support services.
GUIDE TO PRIOR AUTHORIZATION SUBMISSIONS
This guide provides steps and tips when submitting a prior authorization.
GUIDE TO REQUESTING A MEDICAL EXCEPTION
This guide provides templates and tips for submitting a medical exception.
SAMPLE LETTER OF MEDICAL NECESSITY
A sample letter template to use when requesting a medical exception for a patient.
INSURANCE CARRIER CONTACT SHEET
The Insurance Carrier Contact Sheet allows your office to record contact information for the insurance
carriers that are contacted most frequently.
UNDERSTANDING MEDICAL VS PHARMACY BENEFIT INSURANCE CARDS
This overview provides information about distinguishing between medical and pharmacy benefit cards.
Please see full Prescribing Information for important safety information.
© 2016 Biogen.
3
All rights reserved.
12/16
SPZ-US-0362
WELCOME TO THE SPINRAZA READINESS KIT!
The SPINRAZA Readiness Kit provides a comprehensive resource to assist your practice or facility in navigating
formulary decision-making for pharmacy and therapeutics committees, as well as supporting the process to
help gain access and approval of your patient’s treatment once prescribed. This kit provides various resources
to help along the way with
Informing your practice or facility about
the use of SPINRAZA for appropriate
patients. The materials included in this
thumb drive will provide detailed product
information, including SPINRAZA efficacy
and safety
nderstanding the steps to product access.
U
Refer to the printed piece that accompanied this
thumb drive of materials to review these steps.
The action item for each step in the process is
included, as well as tips provided in this kit
ompleting the SPINRAZA Start
C
Form to enroll your patient in
Biogen support services
ubmitting prior authorizations
S
and requesting medical exceptions
Maintaining insurance carrier
contact information
Obtaining approval for your patient’s treatment for spinal muscular atrophy (SMA) often requires your practice
or facility to complete several steps, including conducting a thorough Benefit Investigation to determine if an
authorization and/or exception is needed prior to treatment approval. In addition, your practice or facility may need
to coordinate with a specialty pharmacy to ensure all payer approvals are obtained and the medication is shipped.
Biogen’s SMA360°™ support provides certain services that address nonmedical barriers to access.
These include logistical assistance, product education, insurance benefits investigations, and financial
assistance. A complete list of the SMA360° offerings can be found at SPINRAZA.com/support.
For more information about insurance coverage for SPINRAZA, contact SMA360° at 1-844-4SPINRAZA
(1-844-477-4672), Monday through Friday, 8:30 am to 8:00 pm ET, or contact your Biogen representative.
SMA360° services from Biogen are available only to those who have been prescribed SPINRAZA. SMA360° is available only in the US.
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of
bleeding complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to
each administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient developed a sustained low platelet count
despite continued drug exposure.
Please see following page for additional Important Safety Information.
1
IMPORTANT SAFETY INFORMATION (continued)
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose
of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for
14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as suggested
by observations from the controlled study.
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions
of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because
patients in the controlled study were infants, adverse reactions that are verbally reported could not be assessed
in this study. In the open-label studies, the most common adverse events in later onset patients were headache
(50%), back pain (41%) and post lumbar puncture syndrome (41%).
Please see full Prescribing Information for additional Important Safety Information.
© 2016 Biogen.
2
All rights reserved.
12/16
SPZ-US-0297
COMPANY: Biogen
PRODUCT TRADE NAME: SPINRAZA™
GENERIC NAME: nusinersen
PRODUCT AVAILABILITY (Estimate): end Q4 2016
PRODUCT DESCRIPTION: SPINRAZA is an intrathecal injection indicated for the treatment of spinal
muscular atrophy (SMA) in pediatric and adult patients and is available in 12-mg/5-mL single-dose vials.
How supplied
12-mg/5-mL injection
Packaging
Single-dose glass vial
Carton dimensions
2.28" x 3.15" x 2.56"
Shipping case dimensions
11.25" x 9.5" x 8" or 11.25" x 9.5" x 10.75"
NDC number
64406-058-01
Potential ICD-10 Codes
G12.0 - Infantile spinal muscular atrophy, type I
G12.1 - Other inherited spinal muscular atrophy
G12.8 - Other spinal muscular atrophies and
related syndromes
G12.9 - Spinal muscular atrophy, unspecified
CPT codea
96450 - C
hemotherapy administration, into CNS
(eg, intrathecal), requiring and including
spinal puncture
62270 - Spinal puncture, lumbar, diagnostic
CPT=Current Procedural Terminology; ICD-10=International Classification of Diseases, Tenth Revision; NDC=National Drug Code.
a
Additional codes may be needed for procedures required to properly administer SPINRAZA.
DOSING: Initiate with 4 loading doses. The first 3 loading doses should be administered at 14-day intervals. The
4th loading dose should be administered 30 days after the 3rd dose. A maintenance dose should be administered
once every 4 months therafter.
STORAGE REQUIREMENTS: Store in a refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton
to protect from light. Do not freeze. See product packaging and Prescribing Information for complete list of instructions.
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient developed a sustained low platelet count
despite continued drug exposure.
Please see following page for additional important safety information.
1
IMPORTANT SAFETY INFORMATION (continued)
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose
of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for
14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as suggested
by observations from the controlled study.
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions
of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because
patients in the controlled study were infants, adverse reactions that are verbally reported could not be assessed
in this study. In the open-label studies, the most common adverse events in later onset patients were headache
(50%), back pain (41%) and post lumbar puncture syndrome (41%).
Please see full Prescribing Information for additional important safety information.
Reference: SPINRAZA [Prescribing Information]. Cambridge, MA: Biogen; December 2016.
© 2016 Biogen.
2
All rights reserved.
12/16
SPZ-US-0364
FREQUENTLY
ASKED QUESTIONS
Please see full Prescribing Information for additional Important Safety Information.
SPINAL MUSCULAR ATROPHY
WHAT IS SPINAL MUSCULAR ATROPHY (SMA)?
•S
MA is an autosomal recessive neuromuscular disease that has a significant impact on patients and
their families1,2
•L
ow levels of survival motor neuron (SMN) protein lead to progressive loss of motor neurons1-4
•S
MA is characterized by progressive muscle weakness and atrophy resulting from the degeneration of
motor neurons in the spinal cord1-3,5,6
HOW MANY PEOPLE ARE AFFECTED BY SMA?
•S
MA is a rare disease—an estimated 9000 people in the United States have the disease—and the incidence
ranges from 5.1 to 16.6 per 100,000 live births across all disease severities7-9
HOW WAS SMA PREVIOUSLY TREATED?
• Until the approval of SPINRAZA, there were no FDA-approved treatments indicated for SMA. Medical care
has typically been palliative care, aimed at helping patients with breathing, coughing, swallowing/feeding,
mobility, and other activities of daily living1,5,10
SMA is a leading genetic cause of infant mortality.2,5,6
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient
developed a sustained low platelet count despite continued drug exposure.
Please see following pages for additional Important Safety Information.
2
ABOUT SPINRAZA
WHAT IS SPINRAZA?
•S
PINRAZA is the first and only FDA-approved treatment indicated for SMA in pediatric and adult patients11,12
•S
PINRAZA has been studied in multiple clinical trials across a range of SMA patients, including
presymptomatic and symptomatic patients who had or were likely to develop Type 1, 2, or 3 SMA11
• In a pivotal controlled trial, patients with infantile-onset SMA who were treated with SPINRAZA
demonstrated significant improvement in motor milestones as measured by Hammersmith Infant
Neurologic Exam (HINE) Section 2 as compared to untreated patients 11
• The overall findings of the controlled trial in infantile-onset SMA and the open-label uncontrolled trials
support the effectiveness of SPINRAZA across the range of SMA patients and appear to support the early
initiation of treatment with SPINRAZA11
• In the open-label uncontrolled trials, some presymptomatic and symptomatic patients who had or were
likely to develop Type 1, 2, or 3 SMA11
— Survived to ages unexpected considering the number of SMN2 gene copies of patients enrolled in the
studies
— Achieved milestones such as the ability to sit unassisted, stand, or walk when they would otherwise be
unexpected to do so
— Maintained milestones at ages when they would be expected to be lost
WHAT IS THE MECHANISM OF ACTION FOR SPINRAZA?
• SPINRAZA is an antisense oligonucleotide (ASO) targeted to SMN211
• In laboratory tests and animal studies, SPINRAZA was shown to increase full-length SMN protein by targeting
the process through which it is produced by a gene called survival motor neuron 2 (SMN2)11
IMPORTANT SAFETY INFORMATION (continued)
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose
of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat
testing and further evaluation.
Please see following pages for additional Important Safety Information.
3
HOW IS SPINRAZA ADMINISTERED?
• SPINRAZA should be administered intrathecally by, or under the direction of, healthcare professionals
experienced in performing lumbar punctures11
• Prior to administration, remove 5 mL of cerebrospinal fluid
• Sedation may be considered based on the clinical condition of the patient
• Ultrasound or other imaging techniques may help guide intrathecal administration of SPINRAZA,
particularly in younger patients
WHAT IS THE DOSAGE OF SPINRAZA?
• The recommended dosage is 12 mg (5 mL) per administration11
•S
PINRAZA treatment is initiated with 4 loading doses. The first 3 loading doses should be administered at
14-day intervals. The 4th loading dose should be administered 30 days after the 3rd dose. A maintenance
dose should be administered once every 4 months thereafter11
Day
0
Day
14 days
14
Day
14 days
28
Day
30 days
Every 4 months
58
LOADING DOSING
(approximate days)
MAINTENANCE DOSING
• If a loading dose is delayed or missed, administer SPINRAZA as soon as possible with at least 14 days
between doses and continue dosing as prescribed. If a maintenance dose is delayed or missed, administer
SPINRAZA as soon as possible and continue dosing every 4 months11
• Conduct the following laboratory tests at baseline and prior to each dose of SPINRAZA and as clinically needed:11
— Platelet count
— Prothrombin time; activated partial thromboplastin time
— Quantitative spot urine protein testing
IMPORTANT SAFETY INFORMATION (continued)
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for 14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height
when administered to infants, as suggested by observations from the
controlled study.
Please see following pages for additional Important Safety Information.
4
WHAT IS THE APPROPRIATE DURATION OF USE FOR SPINRAZA?
• The overall findings of the clinical trials support the early initiation of treatment with SPINRAZA1
• Patient improvement may vary and be difficult to measure quantitatively, therefore physician discretion
should be used to evaluate the length of treatment11
ARE THERE ANY CONTRAINDICATIONS FOR SPINRAZA?
• There are no contraindications for SPINRAZA11
ARE THERE WARNINGS AND PRECAUTIONS FOR SPINRAZA?
• Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some ASOs. In a clinical study, 6 of 56 (11%) SPINRAZA-treated patients with
normal or above normal platelet levels at baseline developed a platelet level below the lower limit of normal,
compared with 0 of 28 sham-procedure control patients. No patient had a platelet count <50,000 cells per mcL in
this study and no patient developed a sustained low platelet count despite continued drug exposure. Because of
the risk of thrombocytopenia and coagulation abnormalities from SPINRAZA, patients may be at increased risk of
bleeding complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed11
• Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some ASOs.
SPINRAZA is present in and excreted by the kidney. In a clinical study (mean treatment exposure 7 months), 17 of
51 (33%) SPINRAZA-treated patients had elevated urine protein, compared with 5 of 25 (20%) sham-control patients.
In a group of later-onset SMA patients (mean treatment exposure 34 months), 36 of 52 (69%) had elevated urine
protein. No elevations in serum creatinine or cystatin C were observed in these studies. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose of
SPINRAZA. For urinary protein concentration greater than 0.2 g/L, consider repeat testing and further evaluation11
ARE THERE ADVERSE EVENTS WITH SPINRAZA?
• In the controlled study, the most common adverse reactions that occurred in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were lower respiratory infection,
upper respiratory infection, and constipation. Serious adverse reactions of atelectasis were more frequent in
SPINRAZA-treated patients (14%) than in control patients (5%). Because patients in the controlled study were
infants, adverse reactions that are verbally reported could not be assessed in this study. The most common
adverse events in the open-label studies in later-onset patients were headache, back pain, and post lumbar
puncture syndrome. Most of these events occurred within 5 days of lumbar puncture11
• In an open-label clinical study in infants with symptomatic SMA, severe hyponatremia was reported in a patient
treated with SPINRAZA requiring salt supplementation for 14 months. Two cases of rash were reported in
patients treated with SPINRAZA. Both cases continued to receive SPINRAZA and had spontaneous resolution
of the rash. SPINRAZA may cause a reduction in growth as measured by height when administered to infants,
as suggested by observations from the controlled study. It is unknown whether any effect of SPINRAZA on
growth would be reversible with cessation of treatment11
IMPORTANT SAFETY INFORMATION (continued)
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions
of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because
patients in the controlled study were infants, adverse reactions that are verbally reported could not be assessed
in this study. In the open-label studies, the most common adverse events in
later onset patients were headache (50%), back pain (41%) and post lumbar
puncture syndrome (41%).
Please see following pages for additional Important Safety Information.
5
HOW SHOULD SPINRAZA BE STORED?
•S
tore SPINRAZA in a refrigerator between 2°C and 8°C (36°F - 46°F)11
•K
eep the vial in its original packaging to protect it from light11
• If refrigeration is not available, store SPINRAZA in its original packaging, protected from light, below
30°C (86°F) for up to 14 days11
HOW IS SPINRAZA ORDERED?
• SPINRAZA is supplied as a 12-mg/5-mL (2.4 mg/mL) solution in a single-dose glass vial free
of preservatives11
• SPINRAZA may be ordered through CuraScript Specialty Distributor (SD)/Accredo Specialty Pharmacy (SP).
CuraScript SD/Accredo SP have extensive experience handling and distributing specialty pharmacy products
for a variety of chronic and rare conditions
• For SPINRAZA ordering, CuraScript SD/Accredo SP can be reached at 1-855-778-1510 (phone) or
1-866-579-4655 (fax)
SPINRAZA SUPPORT SERVICES
DOES BIOGEN HAVE SUPPORT SERVICES FOR SPINRAZA?
• Biogen’s SMA360°™ support provides certain services that address nonmedical barriers to access.a These
include logistical assistance, product education, insurance benefits investigations, and financial assistance. A
complete list of the SMA360° offerings can be found at www.SPINRAZA-hcp.com/support
Biogen is committed to supporting patients and those who care for them with a range of
helpful services, financial assistance, and other programs.
SMA360° services from Biogen are only available to those who have been prescribed SPINRAZA. SMA 360° is available only in the US.
a
IMPORTANT SAFETY INFORMATION (continued)
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient
developed a sustained low platelet count despite continued drug exposure.
Please see following page for additional Important Safety Information.
6
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient developed a sustained low platelet count
despite continued drug exposure.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose
of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for
14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as suggested
by observations from the controlled study.
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions
of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because
patients in the controlled study were infants, adverse reactions that are verbally reported could not be assessed
in this study. In the open-label studies, the most common adverse events in later onset patients were headache
(50%), back pain (41%) and post lumbar puncture syndrome (41%).
Please see full Prescribing Information for additional Important Safety Information.
7
References: 1. Wang CH, Finkel RD, Bertini ES, et al; Participants of the
International Conference on SMA Standard of Care. Consensus statement for
standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):
1027-1049. 2. Darras BT. Spinal muscular atrophies. Pediatr Clin North Am.
2015;62(3):743-766. 3. Lunn MR, Wang CH. Spinal muscular atrophy.
Lancet. 2008;371(9630):2120-2133. 4. Tisdale S, Pellizzoni L. Disease
mechanisms and therapeutic approaches in spinal muscular atrophy. J
Neurosci. 2015;35(23):8691-8700. 5. Arnold WD, Kassar D, Kissel JT. Spinal
muscular atrophy: diagnosis and management in a new therapeutic era.
Muscle Nerve. 2015;51(2):157-167. 6. Sugarman EA, Nagan N, Zhu H, et
al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular
atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum
Genet. 2012;20(1):27-32. 7. The Lewin Group, Inc; for Muscular Dystrophy
Association. Cost of Amyotrophic Lateral Sclerosis, Muscular Dystrophy, and
Spinal Muscular Atrophy in the United States: Final Report. https://www.
mda.org/sites/default/files/Cost_Illness_Report.pdf. Published March 1,
2012. Accessed August 17, 2016. 8. Jones C, Zielinski D, Vinikoor L, Farwell
W. Systematic review of incidence and prevalence of spinal muscular
atrophy (SMA). Poster presented at: 11th European Paediatric Neurology
Society Congress 2015. May 27-30, 2015; Vienna, Austria. 9. Biogen,
Data on File. 10. National Institutes of Health; US Department of Health
and Human Services. Spinal muscular atrophy. NIH publication 12-5597.
http://www.ninds.nih.gov/disorders/sma/spinal_muscular_atrophy_FS.pdf.
Published July 2012. Accessed October 6, 2016. 11. SPINRAZA [Prescribing
Information]. Cambridge, MA: Biogen; December 2016. 12. U.S. FDA
approves Biogen’s SPINRAZATM (nusinersen), the first treatment for spinal
muscular atrophy [news release]. Boston, MA: Biogen; December 23, 2016.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm534611.htm. Accessed December 23, 2016.
Please see full Prescribing Information for additional Important Safety Information.
© 2016 Biogen.
All rights reserved.
12/16
SPZ-US-0129
SPINRAZA
CLINICAL OVERVIEW
Please see full Prescribing Information for additional Important Safety Information.
TABLE OF CONTENTS
INDICATION...........................................................................................................3
CONTROLLED STUDY (ENDEAR)...................................................................4
SUPPORTIVE OPEN-LABEL UNCONTROLLED STUDIES............................7
SAFETY...............................................................................................................8
SUMMARY....................................................................................................... 11
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to
zero sham-procedure control patients. No patient had a platelet count
<50,000 cells per mcL and no patient developed a sustained low platelet
count despite continued drug exposure.
Please see following pages for additional Important Safety Information.
2
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
INDICATION
SPINRAZA is the first and only treatment approved by the US Food and Drug Administration indicated for
spinal muscular atrophy (SMA) in pediatric and adult patients.1,2
SPINRAZA has been studied in multiple clinical trials across a range of SMA patients, including presymptomatic
and symptomatic patients who had or were likely to develop SMA Type 1, 2, or 3.1
Infantile-onset SMA
Later-onset SMA
Infantile-onset SMA symptoms typically
appear between birth and 6 months
(most likely to develop SMA Type 1)3,4
Later-onset SMA symptoms typically appear
between ages 6 and 18 months (most likely to
develop SMA Type 2) and between 18 and 36
months (most likely to develop SMA Type 3)3,4
IMPORTANT SAFETY INFORMATION
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen)
at baseline and prior to each dose of SPINRAZA. For urinary protein
concentration >0.2 g/L, consider repeat testing and further evaluation.
Please see following pages for additional Important Safety Information.
3
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
CONTROLLED STUDY IN PATIENTS WITH
INFANTILE-ONSET SPINAL MUSCULAR ATROPHY (ENDEAR)
STUDY DESCRIPTION
• This study was a multicenter, randomized, double-blind, sham-procedure controlled study in 121 symptomatic
infants ≤7 months of age at the time of first dose, diagnosed with spinal muscular atrophy (SMA) (symptom
onset before 6 months of age)1
• A planned interim efficacy analysis was conducted based on patients who died, withdrew, or completed at
least 183 days of treatment1
Day 183
Interim Analysis
Randomized 2:1
Controlled
study
population
(N=121)
SPINRAZAtreated
Sham injection
Day
0
Day
14
days
15
Day
14
days
Day
29
Every
4 months
64
30
days
LOADING
DOSING
MAINTENANCE
DOSING
SPINRAZA
(n=52)
Sham injection
(n=30)
Day
302
Day
394
Key motor function endpoint measures
• HINE
• CHOP INTEND
DESCRIPTION OF MEASUREMENTS IN SPINRAZA CLINICAL TRIALS
Hammersmith Infant Neurological Examination (HINE) Section 2 is a measure comprising different areas of
motor milestone development, with a maximum score of 2 to 4 points for each and a total maximum score
of 26. The primary endpoint assessed at the time of interim analysis was the proportion of responders.1
• A treatment responder was defined as any patient with at least a 2-point increase (or maximal score of 4)
in ability to kick (consistent with improvement by at least 2 milestones), or at least a 1-point increase in the
motor milestones of head control, rolling, sitting, crawling, standing, or walking (consistent with improvement
by at least 1 milestone)
• To be classified as a responder, patients needed to exhibit improvement in more categories of motor
milestones than worsening1
Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) is a 64-point
motor assessment that evaluates muscle strength and function in infants with SMA. Some examples of the
assessments in the CHOP INTEND include spontaneous movement of the upper part of the body, such as
lifting the elbow off of a surface or wrist movement; spontaneous movement of the lower part of the body,
such as raising feet and knees off of a surface and ankle movement; head control; hand grip; elbow flexing;
twisting the pelvis; and rolling.5
IMPORTANT SAFETY INFORMATION (continued)
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for 14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when
administered to infants, as suggested by observations from the controlled
study.
Please see following pages for additional Important Safety Information.
4
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
KEY MOTOR FUNCTION ENDPOINTS
Motor Milestone Response and CHOP INTEND Results1
Endpoint
SPINRAZA-treated
patients (n=52)a
Sham-control patients
(n=30)a
21 (40%);
P<0.0001
0 (0%)
33 (63%)
1 (3%)
2 (4%)
12 (40%)
Motor Milestone (HINE Section 2)a
Achievement of a motor milestone response
CHOP INTEND Improvement From Baselineb
At least 4 points
CHOP INTEND Worsening From Baseline
b
At least 4 points
Analyses included all subjects who were alive with the opportunity for at least a 6-month (Day 183) assessment and all subjects who died
or withdrew from the study at the time of the interim analysis.
a
Not statistically controlled for multiple comparisons at interim analysis.
b
• 40% (P<0.0001) of SPINRAZA-treated patients had achievement of motor milestone (HINE) response,
compared with 0% in the sham-controlled group1
• 63% of SPINRAZA-treated patients had at least a 4-point CHOP INTEND improvement from baseline,
compared with 3% in the sham-controlled group1
• 4% of SPINRAZA-treated patients had at least a 4-point CHOP INTEND worsening from baseline, compared
with 40% in the sham-controlled group1
A significantly greater percentage of SPINRAZA-treated patients achieved a motor milestone response, as
measured by HINE, compared with sham-controlled patients. 1,a
IMPORTANT SAFETY INFORMATION (continued)
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions
of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because
patients in the controlled study were infants, adverse reactions that are verbally reported could not be assessed
in this study. In the open-label studies, the most common adverse events in
later onset patients were headache (50%), back pain (41%) and post lumbar
puncture syndrome (41%).
Please see following pages for additional Important Safety Information.
5
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
KEY MOTOR FUNCTION ENDPOINTS (cont’d)
Net Change From Baseline in Total Motor Milestone Score (HINE) by Percent of Subjects
in the Interim Efficacy Set1,a
SPINRAZA (n=52)
Sham control (n=30)
For subjects who were alive and ongoing in the study, the change in total motor milestone score was calculated at the later of Day 183,
Day 302, or Day 394.
a
In a controlled study, a greater percentage of infantile-onset patients on SPINRAZA survived compared to
untreated patients.1
IMPORTANT SAFETY INFORMATION (continued)
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been observed
after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding complications.
Perform a platelet count and coagulation laboratory testing at baseline and prior to each administration of SPINRAZA
and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to
zero sham-procedure control patients. No patient had a platelet count
<50,000 cells per mcL and no patient developed a sustained low platelet
count despite continued drug exposure.
Please see following pages for additional Important Safety Information.
6
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
SUPPORTIVE OPEN-LABEL UNCONTROLLED STUDIES
Multiple open-label uncontrolled trials were conducted across a range of patients with SMA, including
presymptomatic and symptomatic patients who had or were likely to develop Type 1, 2, or 3 SMA.1
OVERALL FINDINGS
• Overall findings of these open-label uncontrolled trials support the effectiveness of SPINRAZA across a
range of SMA patients1
• The results of the controlled trial in infantile-onset SMA patients were supported by open-label uncontrolled
trials conducted in1
• Symptomatic SMA patients who ranged in age from 30 days to 15 years at the time of first dose
• Presymptomatic patients who ranged in age from 8 days to 42 days at the time of first dose
• The overall findings appear to support the early initiation of treatment with SPINRAZA1
Some patients achieved milestones such as ability to sit unassisted, stand, or walk when they would otherwise
be unexpected to do so; some patients maintained milestones at ages when they would be expected to be lost
and survived to ages unexpected.1
IMPORTANT SAFETY INFORMATION (continued)
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had elevated
urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69% had elevated
urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative spot
urine protein testing (preferably using a first morning urine specimen)
at baseline and prior to each dose of SPINRAZA. For urinary protein
concentration >0.2 g/L, consider repeat testing and further evaluation.
Please see following pages for additional Important Safety Information.
7
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
SAFETY
MOST COMMON ADVERSE REACTIONS
• Clinical trials are conducted under widely varying conditions; adverse reaction rates observed in the clinical
trials of SPINRAZA cannot be directly compared with rates in clinical trials of other drugs and may not reflect
the rates observed in practice1
• The data described below reflect exposure to SPINRAZA in 173 patients, including patients with
presymptomatic SMA, infantile-onset SMA, and later-onset SMA1
• In the controlled study, baseline disease characteristics were largely similar in the SPINRAZA-treated patients
and sham-control patients; however SPINRAZA-treated patients at baseline had a higher percentage
compared with sham-control patients of the following1:
• Paradoxical breathing (89% vs 66%)
• Pneumonia or respiratory symptoms (35% vs 22%)
• Swallowing or feeding difficulties (51% vs 29%)
• Requirement for respiratory support (26% vs 15%)
• There was some imbalance in age at symptom onset with 88% of subjects in the SPINRAZA group and 77% in
the control group experiencing symptoms within the first 12 weeks of life1
Adverse Reactions That Occurred in at Least 5% of SPINRAZA Patients and Occurred at Least 5%
More Frequently or at Least 2 Times as Frequently Than in Control Patients in the Controlled Study
in Infants With Symptomatic SMA1
Adverse Reactions
SPINRAZA 12 mga
(n=80); n (%)
Sham Control
(n=41); n (%)
Lower respiratory infectionb
34 (43)
12 (29)
Upper respiratory infectionc
31 (39)
14 (34)
Constipation
24 (30)
9 (22)
Teething
11 (14)
3 (7)
Upper respiratory tract congestion
5 (6)
1 (2)
Aspiration
4 (5)
1 (2)
Ear infection
4 (5)
1 (2)
Scoliosis
4 (5)
1 (2)
Four loading doses followed by 12 mg (5 mL) once every 4 months.
Includes pneumonia, bronchiolitis, pneumonia viral, respiratory syncytial virus bronchiolitis, lower respiratory tract infection, pneumonia
bacterial, bronchitis, bronchitis viral, pneumonia moraxella, pneumonia parainfluenzae viral, lower respiratory tract infection viral, lung
infection, pneumonia influenza, pneumonia pseudomonal, pneumonia respiratory syncytial viral.
c
Includes upper respiratory tract infection, nasopharyngitis, rhinitis, pharyngitis, or tracheitis.
a
b
IMPORTANT SAFETY INFORMATION (continued)
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for 14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height
when administered to infants, as suggested by observations from the
controlled study.
Please see following pages for additional Important Safety Information.
8
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
MOST COMMON ADVERSE REACTIONS (cont’d)
• In the controlled study, the most common adverse reactions that occurred in at least 20% of SPINRAZAtreated patients and occurred at least 5% more frequently than in control patients were upper respiratory
infection, lower respiratory infection, and constipation. Serious adverse reactions of atelectasis were more
frequent in SPINRAZA-treated patients (14%) than in control patients (5%)1
• In the open-label studies in later-onset patients, the most common adverse reactions were headache (50%),
back pain (41%), and post lumbar puncture syndrome (41%), most of which occurred within 5 days following
lumbar puncture1
• Other adverse events in these patients were consistent with adverse reactions observed in the
controlled study1
• Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation
for 14 months1
• Two cases of rash were reported in patients treated with SPINRAZA. Both cases continued to receive
SPINRAZA and had spontaneous resolution of the rash1
• SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as
suggested by observations from the controlled study1
LABORATORY TESTING AND MONITORING TO ASSESS SAFETY
Conduct the following laboratory tests at baseline and prior to each dose of SPINRAZA and as clinically
needed1:
• Platelet count
• Prothrombin time; activated partial thromboplastin time
• Quantitative spot urine protein testing
IMPORTANT SAFETY INFORMATION (continued)
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions of
atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because patients
in the controlled study were infants, adverse reactions that are verbally
reported could not be assessed in this study. In the open-label studies,
the most common adverse events in later onset patients were headache
(50%), back pain (41%) and post lumbar puncture syndrome (41%).
Please see following pages for additional Important Safety Information.
9
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
WARNINGS AND PRECAUTIONS
Thrombocytopenia and Coagulation Abnormalities
• Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides1
• In a clinical study, 6 of 56 (11%) SPINRAZA-treated patients with normal or above normal platelet levels at
baseline developed a platelet level below the lower limit of normal, compared with 0 of 28 sham-procedure
control patients. No patient had a platelet count less than 50,000 cells per microliter in this study and no
patient developed a sustained low platelet count despite continued drug exposure1
• Because of the risk of thrombocytopenia and coagulation abnormalities from SPINRAZA, patients may be at
increased risk of bleeding complications1
Renal Toxicity
• Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides1
• SPINRAZA is present in and excreted by the kidney. In a clinical study (mean treatment exposure 7 months),
17 of 51 (33%) SPINRAZA-treated patients had elevated urine protein, compared with 5 of 25 (20%) shamcontrol patients. In a group of later-onset SMA patients (mean treatment exposure 34 months), 36 of 52 (69%)
had elevated urine protein. No elevations in serum creatinine or cystatin C were observed in these studies.
Conduct quantitative spot urine protein testing (preferably using a first morning urine specimen) at baseline
and prior to each dose of SPINRAZA. For urinary protein concentration greater than 0.2 g/L, consider repeat
testing and further evaluation1
IMPORTANT SAFETY INFORMATION (continued)
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to
zero sham-procedure control patients. No patient had a platelet count
<50,000 cells per mcL and no patient developed a sustained low platelet
count despite continued drug exposure.
Please see following pages for additional Important Safety Information.
10
CONTROLLED STUDY
(ENDEAR)
SUPPORTIVE OPEN-LABEL
UNCONTROLLED STUDIES
SAFETY
SUMMARY
SUMMARY
• Clinical trials support the effectiveness of SPINRAZA across the range of patients with SMA and appear to
support the early initiation of treatment with SPINRAZA1
• In a pivotal controlled study the safety and efficacy of SPINRAZA was demonstrated in infantile-onset SMA1
• In open-label uncontrolled studies, the safety and efficacy of SPINRAZA was demonstrated in symptomatic
and presymptomatic patients who had or were likely to develop Type 1, 2, or 3 SMA1
• Some patients treated with SPINRAZA
­— Survived to ages unexpected
— Achieved milestones such as ability to sit unassisted, stand, or walk when they would otherwise be
unexpected to do so
— Maintained milestones at ages when they would be expected to be lost
• Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides1
• Because of the risk of thrombocytopenia and coagulation abnormalities from SPINRAZA, patients may be
at increased risk of bleeding complications
• Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides1
• SPINRAZA is present in and excreted by the kidney. In a clinical study (mean treatment exposure
7 months), 17 of 51 (33%) SPINRAZA-treated patients had elevated urine protein, compared with 5 of 25
(20%) sham-control patients
• In the controlled study, the most common adverse reactions that occurred in at least 20% of SPINRAZAtreated patients and occurred at least 5% more frequently than in control patients were1
• Upper respiratory infection
• Lower respiratory infection
• Constipation
IMPORTANT SAFETY INFORMATION (continued)
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen)
at baseline and prior to each dose of SPINRAZA. For urinary protein
concentration >0.2 g/L, consider repeat testing and further evaluation.
Please see following page for additional Important Safety Information.
11
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of
bleeding complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to
each administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient developed a sustained low platelet count
despite continued drug exposure.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose
of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for
14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as suggested
by observations from the controlled study.
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection
(39% vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse
reactions of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%).
Because patients in the controlled study were infants, adverse reactions that are verbally reported could not be
assessed in this study. In the open-label studies, the most common adverse events in later onset patients were
headache (50%), back pain (41%) and post lumbar puncture syndrome (41%).
Please see full Prescribing Information for additional Important Safety Information.
12
References: 1. SPINRAZA [Prescribing Information]. Cambridge,
MA: Biogen; December, 2016. 2. U.S. FDA approves Biogen’s
SPINRAZA™ (nusinersen), the first treatment for spinal muscular
atrophy [news release]. Boston, MA: Biogen; December 23, 2016.
http://media. biogen.com/press-release/neurodegenerative-diseases/
us-fda-approves-biogens-spinraza-nusinersen-first-treatment.
Accessed December 23, 2016. 3. Finkel R, Bertini E, Muntoni F,
et al; ENMC SMA Workshop Study Group. 209th ENMC International
Workshop: outcome measures and clinical trial readiness in spinal muscular
atrophy 7–9 November 2014, Heemskerk, the Netherlands. Neuromuscul Disord.
2015;25(7):593-602. 4. Darras BT. Spinal muscular atrophies. Pediatr Clin North Am.
2015;62(3):743-766. 5. Glanzman AM, Mazzone E, Main M, et al. The Children’s
Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND):
test development and reliability. Neuromuscul Disord. 2010;20(3):155-161.
Please see full Prescribing Information for additional Important Safety Information.
© 2016 Biogen.
All rights reserved.
12/16
SPZ-US-0128
TIPS TO SUCCESSFULLY
COMPLETING A
SPINRAZA START FORM
Please see full Prescribing Information for
additional Important Safety Information.
YOUR GUIDE TO COMPLETING THE
SPINRAZA™ (nusinersen) START FORM
Completing the SPINRAZA Start Form provides your patient with an opportunity to join SMA360°TM, a
support service from Biogen. The SPINRAZA Start Form is not a prescription and is not required for patients
to begin treatment.
As a reminder, Biogen’s SMA360° support provides certain services that address nonmedical barriers to access.
These include logistical assistance, product education, insurance benefit investigation, and financial assistance.
A complete list of the SMA360° offerings can be found at www.spinraza-hcp.com/support. SMA360° services
from Biogen are available only to those who have been prescribed SPINRAZA.
This guide will help you identify the key information needed to complete a SPINRAZA Start Form.
SPINRAZA START FORM SECTIONS FOR YOUR PATIENTS’ PARENTS OR GUARDIANS
The following sections of the SPINRAZA Start Form are reviewed and signed or checked off by the parent or
guardian of your patient. Each SPINRAZA Start Form has an accompanying Patient Consent Information page
that explains why this information is needed. Remember to discuss the Patient Consent Information page with
the parent/guardian of your patient when he or she reviews and signs the SPINRAZA Start Form.
A
B
C
Authorization to share
health information for
Biogen support services
and marketing/other
communications
Opt in for automated
marketing calls
and text messages
Patient
information
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing
at baseline and prior to each administration of SPINRAZA and as
clinically needed.
Please see following pages for additional Important Safety Information.
2
B:8.75”
T:8.5”
S:8”
START FORM
Phone: 1-844-4SPINRAZA (1-844-477-4672) Fax: 1-888-538-9781
AUTHORIZATION TO SHARE HEALTH INFORMATION
FOR PATIENT SUPPORT SERVICES AND MARKETING/
OTHER COMMUNICATIONS
I have read and understand the Authorization to Share Health Information
for Patient Support Services and Marketing/Other Communications and
agree to the terms.
Signature of patient or parent/guardian (if under 18)
Date
In addition, I authorize the disclosure of my health information to the
following designated individual(s) (optional):
Name (print)
Relationship
OPT-IN FOR AUTOMATED MARKETING CALLS AND
TEXT MESSAGES
A
Authorization to share
health information for
patient support services
and marketing/other
communications
PATIENT INFORMATION
First name
Male
Last name
Female
Date of birt
CONTACT INFORMATION
Email address
Preferred
Home telephone
Cell phone
Best time to contact
Preferred
Morning
Afternoon
The signature
the
in this section
I haveof
read
and patient
understandor
the parent/guardian
Opt-In for Automated Marketing
Address authorizes the
and Text Messages and hereby agree to receive these
healthcareCalls
providers,
insurance
company,
and
pharmacy
providers to share
types of communications from Biogen (optional).
City
State
the patient’s
confidential
health
information
with
Biogen.
This
allows Biogen
Signatures/information required in order to receive Biogen services.
Spanish is my primary language
to forward the patient’s prescription to the dedicated specialty pharmacy,
THE FOLLOWING INFORMATION MUST BE FILLED OUT BY YOUR HEALTHCARE PROVIDER IN ORDER TO RECEIVE BIOGEN
and will authorize
the specialty pharmacy to share information with Biogen,
This form is not a prescription.
Please completeyour
this form
and fax directly
to Biogen.
if necessary.
It also authorizes
patient’s
confidential
health information
toPRESCRIBER
be shared for
purposes of SMA360° support services, including
financial
INFORMATION
FACILITY/SITE
OF CARE/PLACE OF S
Please complete this section if different from pres
assistance.
First name
Last name
Check box if you desire support in locating a facility/s
Please note that Biogen may use this information for internal
and
Facility planning
name
City
State
ZIP code
research.
Address
Address
Telephone
Email
City
The patient or parent/guardian will sign and date this section. Guardians
NPI #
license #
ID #
Facility contact name
should
explain theirState
authority
to act onTaxthe
patient’s behalf.
Clinic/Hospital affiliation
Facility fax number
Is this where the appointment/administration will take place?
Site of care/POS code
YES
NO
Physician office (11)
State
Facility conta
NPI #
Outpatien
If no, please complete Facility/Site of Care/Place of Service Information section.
Inpatient (21) Observation a possibility in lieu of inpa
Any procedural requirements? (eg, anesthesia, sedation, etc)
Ambulatory surgical center (24)
Primary diagnosis: ICD-10 G12.0, G12.1, G12.8, or G12
Last name
Date of symptom onset:
Office contact name
Signing Section A of the SPINRAZASpecialty
Start Form enrolls your patient
in SMA360°, which provides extra
Group #to those
support services and resources, asOffice
needed.
SMA360° services
from
Biogen are only available
contact telephone
Office
fax number
Preferred method of contact
Telephone
Email
Fax
who have been prescribed SPINRAZA.
Policyholder’s first name
Primary insurance
Best time to contact
Morning
Other
MEDICAL INSURANCE INFORMATIO
Who is the physician administering treatment?
First name
Outpatient on campus (ie. infusion, short stay, surgica
Afternoon
ADMINISTRATION PLAN
Please provide all details concerning dosing schedule (ie, number of loading
doses, maintenance doses).
IMPORTANT SAFETY INFORMATION
(continued)
Date(s) of Loading Dose(s)
Policy #
Insurance co
Policyholder
Secondary insurance
Policy/group
Medicaid/governmental payer
*Please reme
of insurance
PRESCRIBER AUTHORIZATION
I authorize
as my designated agent on behalf o
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels
atBiogen
baseline
information on this form to his/her insurer.
1st loading dose
2nd loading dose
3rd loading dose
4th loading dose
developed a platelet level below the lower limit of normal compared to zero sham-procedure
control patients.
I will either administer treatment or supervise the treatme
Date(s) of Maintenance Dose(s) (if applicable)
No patient had a platelet count <50,000
cells per mcL and no patient developed a sustained low platelet count
Prescriber signature
despite continued drug exposure.
Next scheduled maintenance dose
Previous maintenance dose
Signature stamps not acceptable.
Special instructions
Renal toxicity, including potentially fatal
glomerulonephritis, has been observed after administration of some
12/16 SPZ-US-0169
antisense oligonucleotides.
SPINRAZA is present in and excretedSMUS16CDNY6408_SPINRAZA_Start_Form_r32.indd
by the kidney. In a clinical 1study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group
of later-onset SMA patients, 69% had elevated urine protein.
Please see following pages for additional Important Safety Information.
3
OTHER COMMUNICATIONS
First name
I have read and understand the Authorization to Share Health Information
for Patient Support Services and Marketing/Other Communications and
agree to the terms.
Signature of patient or parent/guardian (if under 18)
Male
CONTACT INFORMATION
Date
In addition, I authorize the disclosure of my health information to the
following designated individual(s) (optional):
Name (print)
Email address
Home telephone
Relationship
Cell phone
OPT-IN FOR AUTOMATED MARKETING CALLS AND
TEXT MESSAGES
Best time to contact
I have read and understand the Opt-In for Automated Marketing
Calls and Text Messages and hereby agree to receive these
types of communications from Biogen (optional).
Opt in for automated
marketing calls and text
messages
Phone: 1-888-4-SPINRAZA (477-4672) Fax: 1-888-538-9781
AUTHORIZATION TO SHARE HEALTH INFORMATION
FOR PATIENT SUPPORT SERVICES AND MARKETING/
OTHER COMMUNICATIONS
I have read and understand the Authorization to Share Health Information
for Patient Support Services and Marketing/Other Communications and
agree to the terms.
Signature of patient or parent/guardian (if under 18)
Date
In addition, I authorize the disclosure of my health information to the
following designated individual(s) (optional):
Parent/guardian (print name)
City
Relationship
OPT-IN FOR AUTOMATED MARKETING CALLS AND
TEXT MESSAGES
I have read and understand the Opt-In for Automated Marketing
Calls and Text Messages and hereby agree to receive these types of
communications from Biogen (optional).
C
Signatures/information required in order to receive Biogen services.
Patient information
Spanish is my primary language
THE FOLLOWING INFORMATION MUST BE FILLED OUT BY YOUR HEALTHCARE PROVIDER IN ORDER TO RE
The patient’s parent/guardian should check the optional box in Section B
This form is not a prescription. Please complete this form and fax directly to Biogen.
ifT:8.5”
they
consent to receive auto dialed and prerecorded marketing calls and
S:8”PRESCRIBER INFORMATION
text messages from SMA360°, Biogen, and companies working FACILITY/SITE
with Biogen. OF CARE/P
B:8.75”
Please complete this section if differ
First name
TART FORM
Morning
Address
Signatures/information required in order to receive Biogen services.
B
Female
Last name
Check box if you desire support in loc
Address
Facility name
City
PATIENT INFORMATION
Telephone
ZIP code
Address
Email
First name
NPI # Male
State
City
Last name
State license #
Female
Tax ID #
Date of birth
Facility contact name
CONTACT
INFORMATION
Clinic/Hospital
affiliation
Facility fax number
Is this where the appointment/administration will take place?
Site of care/POS code
Email address
YES
Physician office (11)
NO
Preferred number OK to leave message
Home
telephone
If no,
please
complete Facility/Site of Care/Place of Service Information section.
Preferred number
OK to leave message
phone
AnyCell
procedural
requirements? (eg, anesthesia, sedation, etc)
Best time to contact
Morning
Afternoon
Inpatient (21) Observation a possibil
Outpatient on campus (ie. infusion, sh
Ambulatory surgical center (24)
Evening
MEDICAL INSURANCE INF
Address
Who
is the physician administering treatment?
City
State
First name
Spanish is my primary language
Specialty
Last name
Primary diagnosis: ICD-10 G12.0, G12.1
ZIP code
Date of symptom onset:
Primary insurance
Office contact name
THE FOLLOWING INFORMATION MUST BE FILLED OUT BY YOUR HEALTHCARE PROVIDER IN ORDER TO RECEIVE BIOGEN SERVICES.
section
includes
Office
contact telephone
s form is not a prescription. Please complete this form and fax directly to Biogen. This
RESCRIBER INFORMATION
t name
Last name
ADMINISTRATION PLAN
dress
Medicaid/governmental payer
Please provide all details concerning dosing schedule (ie, number of loading
Email
#
State license #
Tax ID #
1st loading dose
Facility contact name
2nd loading dose
3rd loading dose
Facility contact telephone
4th loading dose
Date(s) of Maintenance Dose(s) (if applicable)
Facility fax(continued)
number
IMPORTANT SAFETY INFORMATION
T:11”
ephone
ZIP code
B:11.25”
State
Facility name
The
patient’s
parent/guardian
completes this section. Your practice or
doses,
maintenance
doses).
Address
facility
should
review
what
the
parent/guardian completed with PRESCRIBER
him or her AUTHORIZAT
Date(s) of Loading Dose(s)
to ensure
accuracy.
I
authorize Biogen as my designated ag
City
State
ZIP code
S:10.5”
y
nic/Hospital affiliation
Group
#
basic information
that will familiarize Biogen
with
Office fax number
your
patient.
gender,
of birth,
name,
address, email
address,
Preferred
methodItofincludes
contact
Telephone
Email
Fax
Policyholder’s
first name
FACILITY/SITE
OF CARE
/PLACEdate
OF SERVICE
(POS)
Besttelephone
time tocomplete
contact numbers,
Afternoon
Please
this section ifMorning
different
fromas
prescriber
information.
and
as well
preference
for the best time to reach
Secondary insurance
Check box ifparent/guardian.
you desire support in locating a facility/site of care /place of service.
the patient’s
information on this form to his/her insur
I will either administer treatment or supe
NPI #
Prescriber signature
NextSite
scheduled
maintenance
dose
Previous maintenance
dose
of C
care/POS
code
or cystatin
were
observed
in studies
with SPINRAZA.
Conduct quantitative
Signature stamps not acceptable.
office (11)
Outpatient off-campus clinic (19)
YES
NO
SpecialPhysician
instructions
spot urine protein testing (preferably using
a first
morning urine specimen)
at baseline and prior to each dose of
Inpatient
(21)
Observation
a
possibility
in
lieu
of
inpatient
admission?
Yes
No
o, please complete Facility/Site of Care /Place of Service Information section.
SPINRAZA. For urinary protein concentration
>0.2
repeat
testing
12/16 SPZ-US-0169
Outpatient
on g/L,
campusconsider
(ie. infusion, short
stay, surgical
suite) (22) and further evaluation.
No elevations inwillserum
creatinine
his where the appointment/administration
take place?
y procedural requirements? (eg, anesthesia, sedation, etc)
Ambulatory surgical center (24)
Other
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for
MEDICAL INSURANCE INFORMATION
14 months.
SMUS16CDNY6408_SPINRAZA_Start_Form_r32.indd 1
o is the physician administering treatment?
t name
Primary diagnosis: ICD-10 G12.0, G12.1, G12.8, or G12.9
Date of symptom onset:
Cases of rash
were reported in patients treated
with SPINRAZA.
Last name
Primary insurance
Policy #
Secondary insurance
Policy/group #
Office contact name
SPINRAZA may
cause a reduction in growth as measured by height when
#
tofaxinfants,
as suggested byGroup
observations
from the Insurance company telephone
fice contact telephoneadministered
Office
number
controlled
Policyholder’s first name
Policyholder’s last name
ferred method of contact
Telephone studyEmail
Fax
ecialty
t time to contact
Morning
Afternoon
DMINISTRATION
PLAN see following pages for additional Important Safety Information.
Please
ase provide all details concerning dosing schedule (ie, number of loading
ses, maintenance doses).
4 Dose(s)
te(s) of Loading
Medicaid/governmental payer
PRESCRIBER AUTHORIZATION
I authorize Biogen as my designated agent and on behalf of my patient to forward
the above statement of medical necessity and furnish any information on this form
to the insurer of the above-named patient.
Patient Section Quick Tips
Here is a checklist of the key sections of the SPINRAZA Start Form to be signed or checked off by
patients’ parents or guardians
Section A
ignature for sharing of the patient’s confidential health information between your office, the
S
insurance company, SMA360°, Biogen, and other companies working with Biogen (such as a
specialty pharmacy)
Section B
Check to opt in for automated marketing calls and text messages
Section C
Complete contact information to familiarize Biogen with the patient
SPINRAZA START FORM SECTIONS FOR PRACTICES OR FACILITIES TO COMPLETE
The following sections of the SPINRAZA Start Form should be completed by your practice or facility:
1
2
3
4
5
Prescriber
information
Administration
plan
Facility/site of
care/place of
service (POS)
Medical
insurance
information
Prescriber
authorization
IMPORTANT SAFETY INFORMATION (continued)
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions
of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because
patients in the controlled study were infants, adverse reactions that are verbally reported could not be assessed
in this study. In the open-label studies, the most common adverse events in
later onset patients were headache (50%), back pain (41%) and post
lumbar puncture syndrome (41%).
Please see following pages for additional Important Safety Information.
5
OPT-IN FOR AUTOMATED MARKETING CALLS AND
TEXT MESSAGES
I have read and understand the Opt-In for Automated Marketing
Calls and Text Messages and hereby agree to receive these types of
communications from Biogen (optional).
Signatures/information required in order to receive Biogen services.
Cell phone
Best time to contact
Morning
Afternoon
Address
City
State
Spanish is my primary language
THE FOLLOWING INFORMATION MUST BE FILLED OUT BY YOUR HEALTHCARE PROVIDER IN ORDER TO RECEIVE BIOGEN
This form is not a prescription. Please complete this form and fax directly to Biogen.
PRESCRIBER INFORMATION
First name
FACILITY/SITE OF CARE /PLACE OF S
Please complete this section if different from pres
Last name
Check box if you desire support in locating a facility/s
Address
Facility name
City
State
Telephone
Email
ZIP code
City
State
Facility contact name
Facility conta
Clinic/Hospital affiliation
Facility fax number
NPI #
Is this where the appointment/administration will take place?
Site of care/POS code
NPI #
YES
State license #
Tax ID #
NO
If no, please complete Facility/Site of Care /Place of Service Information section.
Any procedural requirements? (eg, anesthesia, sedation, etc)
Prescriber
information
Outpatient on campus (ie. infusion, short stay, surgica
Other
Primary diagnosis: ICD-10 G12.0, G12.1, G12.8, or G12
Last name
Specialty
Office contact name
Office contact telephone
Office fax number
Best time to contact
Outpatien
Inpatient (21) Observation a possibility in lieu of inpa
MEDICAL INSURANCE INFORMATIO
First name
Preferred method of contact
Physician office (11)
Ambulatory surgical center (24)
Who is the physician administering treatment?
1
Address
Telephone
Email
Morning
Afternoon
Date of symptom onset:
Fax
ADMINISTRATION PLAN
Primary insurance
Policy #
Group #
Insurance co
Policyholder’s first name
Policyholder
Secondary insurance
Policy/group
Medicaid/governmental payer
Please provide all details concerning dosing schedule (ie, number of loading
The
prescribing physician completes this section. This may or may not be the
doses, maintenance doses).
PRESCRIBER
AUTHORIZATION
same person who administers the injection. Please include
your email
address
Date(s) of Loading Dose(s)
I authorize Biogen as my designated agent and on beh
and all information requested.
the above statement of medical necessity and furnish an
1st loading dose
2nd loading dose
3rd loading dose
4th loading dose
to the insurer of the above-named patient.
I will either administer treatment or supervise the treatme
If “yes”
is checked for the question that asks if the appointment/administration
Date(s) of Maintenance Dose(s) (if applicable)
will take place at the prescriber’s practice or facility, the prescriber information
Prescriber signature
scheduled maintenance
dose location
Previous
maintenance
dose
is Next
assumed
to be the
where
the treatment
will beSignature
administered.
If you
stamps not acceptable.
Special
plan
toinstructions
administer treatment at a location other than the information provided,
11/16 SPZ-US-0169
please
check “no” and complete the section Facility/Site of Care/Place of
Service on the top right portion of the Start Form (see page 7 of this guide for
more information).
SMUS16CDNY6408_SPINRAZA_Start_Form_r18.indd 1
At the bottom of the Prescriber Information section, please provide information
about the healthcare professional who will administer treatment. Even if you are
both the prescriber and administering physician, please complete the form.
IMPORTANT SAFETY INFORMATION (continued)
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient
developed a sustained low platelet count despite continued drug exposure.
Please see following pages for additional Important Safety Information.
6
MEDICAL INSURANCE INFORMATIO
B:8.75”
T:8.5”
S:8”
RT FORM
Phone: 1-888-4-SPINRAZA (477-4672) Fax: 1-888-538-9781
THORIZATION TO SHARE HEALTH INFORMATION
R PATIENT SUPPORT SERVICES AND MARKETING/
HER COMMUNICATIONS
ve read and understand the Authorization to Share Health Information
Patient Support Services and Marketing/Other Communications and
ee to the terms.
ature of patient or parent/guardian (if under 18)
Date
ddition, I authorize the disclosure of my health information to the
owing designated individual(s) (optional):
2
nt/guardian (print name)
Relationship
PT-IN FOR AUTOMATED MARKETING CALLS AND
XT MESSAGES
Administration
have read and understand the Opt-In for Automated Marketing
alls and Text Messages and hereby agreeplan
to receive these types of
ommunications from Biogen (optional).
natures/information required in order to receive Biogen services.
Who is the physician administering treatment?
Primary diagnosis: ICD-10 G12.0, G12.1, G12.8, or G12
First name
Last name
Date of symptom onset:
Specialty
Office contact name
Primary insurance
Policy #
Group #
Insurance co
Office contact telephone
Office fax number
Preferred method of contact
Best time to contact
Telephone
Email
Morning
Fax
Afternoon
PATIENT INFORMATION
ADMINISTRATION PLAN
First
name
Last name
Please
provide all details concerning dosing
schedule (ie, number of loading
doses, maintenance doses).
Male
Female
Date(s) of Loading Dose(s)
CONTACT
INFORMATION
1st loading dose
2nd loading dose
Special instructions
Cell phone
Best
time
to contact
12/16
SPZ-US-0169
Morning
Policyholder
Secondary insurance
Policy/group
Medicaid/governmental payer
*Please reme
of insurance
PRESCRIBER AUTHORIZATION
Date of birth
3rd loading dose
4th loading dose
I authorize Biogen as my designated agent on behalf o
information on this form to his/her insurer.
I will either administer treatment or supervise the treatme
Date(s)
of Maintenance Dose(s) (if applicable)
Email
address
Home
telephonemaintenance dose
Next scheduled
Policyholder’s first name
Preferred number OK to leave message
Previous maintenance dose
Preferred number
OK to leave message
Afternoon
Evening
Prescriber signature
Signature stamps not acceptable.
Address
Administration
of SPINRAZA1 requires 4 loading doses followed by
SMUS16CDNY6408_SPINRAZA_Start_Form_r32.indd
City
State
ZIP code
maintenance
doses
every 4 months. Please provide information about
Spanish is my primary language
the proposed dates of future doses.
THE FOLLOWING INFORMATION MUST BE FILLED OUT BY YOUR HEALTHCARE PROVIDER IN ORDER TO RECEIVE BIOGEN SERVICES.
m is not a prescription. Please complete this form and fax directly to Biogen.
CRIBER INFORMATION
me
FACILITY/SITE OF CARE /PLACE OF SERVICE (POS)
Please complete this section if different from prescriber information.
Last name
Check box if you desire support in locating a facility/site of care /place of service.
s
Facility name
State
Tax ID #
ospital affiliation
where the appointment/administration will take place?
NO
ease complete Facility/Site of Care /Place of Service Information section.
3
cedural requirements? (eg, anesthesia, sedation, etc)
Facility/
site of care/POS
he physician administering treatment?
me
Last name
y
Office contact name
ontact telephone
Office fax number
Telephone
d method of contact
Morning
e to contact
INISTRATION PLAN
Email
Afternoon
Fax
provide all details concerning dosing schedule (ie, number of loading
maintenance doses).
State
ZIP code
Facility contact name
Facility contact telephone
Facility fax number
NPI #
T:11”
State license #
City
B:11.25”
Email
Address
S:10.5”
ne
ZIP code
Site of care/POS code
Physician office (11)
Outpatient off-campus clinic (19)
Inpatient (21) Observation a possibility in lieu of inpatient admission? Yes
No
Outpatient on campus (ie. infusion, short stay, surgical suite) (22)
Ambulatory surgical center (24)
Other
MEDICAL INSURANCE INFORMATION
Primary diagnosis: ICD-10 G12.0, G12.1, G12.8, or G12.9
Date of symptom
onset: the facility/site of care/POS information if your contact
Please
complete
details
are
different
from the
prescriber information. It is important to
Primary insurance
Policy #
provide a contact name and number for the facility where SPINRAZA should
Group #
Insurance company telephone
be delivered.
Policyholder’s first name
Policyholder’s last name
In addition, please provide details about your facility by checking the box
Secondary
insurance the POS code.
Policy/group
#
that
indicates
It is also
important to note if observation of
your
patient is apayer
possibility in lieu of inpatient admission.
Medicaid/governmental
PRESCRIBER AUTHORIZATION
I authorize Biogen as my designated agent and on behalf of my patient to forward
IMPORTANT SAFETY INFORMATION
(continued)
the above statement of medical necessity and furnish any information on this form
) of Loading Dose(s)
to the insurer of the above-named patient.
3rd loading
dose
4th loading
dose
Renal toxicity,
including
potentially
fatal
glomerulonephritis, has been observed after administration of some
I will either administer treatment or supervise the treatment accordingly.
antisense
oligonucleotides.
) of Maintenance Dose(s)
(if applicable)
ing dose
2nd loading dose
Prescriber signature
Date
maintenancein
dose
SPINRAZAPrevious
is present
and excreted by
the kidney. In a clinical study, 33%
of SPINRAZA-treated patients had
Signature stamps not acceptable.
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
heduled maintenance dose
instructions
PZ-US-0169
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose
NY6408_SPINRAZA_Start_Form_r18.indd 1
11/9/16 1:22 PM
of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat testing
and further evaluation.
Please see following pages for additional Important Safety Information.
7
Facility fax number
NPI # OF SERVICE (POS)
FACILITY/SITE
OF CARE/PLACE
where the appointment/administration
will take place?
me
Last name
NO
ease complete Facility/Site of Care/Place of Service Information section.
State sedation, etc)
ZIP code
ocedural requirements? (eg, anesthesia,
State license #
me
Please complete this section if different from prescriber information.
Site of care/POS code
Check box if you desire support in locating a facility/site of care/place of service.
Physician office (11)
Outpatient off-campus clinic (19)
Inpatient (21) Observation a possibility in lieu of inpatient admission? Yes
Facility name
Outpatient on campus (ie. infusion, short stay, surgical suite) (22)
Ambulatory surgical center (24)
Address
MEDICAL INSURANCE
City
Email
the physician administering treatment?
Tax ID #
Last name
Facility contact telephone
Other
INFORMATION*
State
ZIP code
Primary diagnosis: ICD-10 G12.0, G12.1, G12.8, or G12.9
Facility contact name
Facility contact telephone
Date of symptom onset:
ospital affiliation
y
Office contact name
Facility fax number
Primary insurance
NPI #
Policy #
ontact
NOtelephone
Office fax number
Group
#
Physician
office (11)
Insurance
company
telephone
Outpatient
off-campus
clinic (19)
where the appointment/administration will take place?
d method
of contact
Email Information
Faxsection.
ease
complete
Facility/SiteTelephone
of Care/Place of Service
e to contact
Morning
Afternoon
ocedural requirements? (eg, anesthesia, sedation, etc)
4
INISTRATION PLAN
provide all details concerning dosing schedule (ie, number of loading
the physician administering
treatment?
maintenance
doses).
) of Loading Dose(s)
me
y dose
ing
2nd loading dose
Medical
insurance
Office
contactdose
name
3rd
loading
4th loading dose
information
Last name
)ontact
of Maintenance
telephone Dose(s) (if applicable)
Office fax number
d method of contact
Telephone
heduled maintenance dose
e to contact
Morning
instructions
Email
Fax
Previous maintenance dose
Afternoon
INISTRATION
PLAN
PZ-US-0169
provide all details concerning dosing schedule (ie, number of loading
maintenance doses).
)NY6408_SPINRAZA_Start_Form_r32.indd
of Loading Dose(s)
1
ing dose
3rd loading dose
2nd loading dose
4th loading dose
Previous maintenance dose
nstructions
5
PZ-US-0169
Prescriber
authorization
NY6408_SPINRAZA_Start_Form_r32.indd 1
Site of care/POS code
Inpatient (21) Observation a possibility in lieu of inpatient admission? Yes
Policyholder’s first name
Policyholder’s last name
Outpatient on campus (ie. infusion, short stay, surgical suite) (22)
Secondary
insurance
Ambulatory
surgical center (24)
No
Policy/group
#
Other
*Please remember to fax front and back copy
Medicaid/governmental
payer
of insurance card(s) along with this Start Form.
MEDICAL
INSURANCE
INFORMATION*
Primary diagnosis: ICD-10 G12.0, G12.1, G12.8, or G12.9
Date of symptom onset:
PRESCRIBER
AUTHORIZATION
I authorize Biogen as my designated agent on behalf of my patient to furnish any
This
section
beinsurer.
completed
in addition to sending a faxed copy of
information
on thisshould
form to his/her
Primary insurance
Policy #
the
front
and back
oforthe
covered
patient’s
I will
either administer
treatment
supervise
the treatment
accordingly. insurance card along with the
Group #
Insurance company telephone
SPINRAZA Start Form. Please be sure to include all forms of the patient’s
Prescriber
signature
Policyholder’s
first
name
insurance
inname
this section. Policyholder’s lastDate
Signature stamps not acceptable.
Secondary insurance
Policy/group #
Medicaid/governmental payer
*Please remember to fax front and back copy
of insurance card(s) along with this Start Form.
PRESCRIBER AUTHORIZATION
12/22/16 5:00 PM
I authorize Biogen as my designated agent on behalf of my patient to furnish any
information on this form to his/her insurer.
I will either administer treatment or supervise the treatment accordingly.
) of Maintenance Dose(s) (if applicable)
heduled maintenance dose
No
S:10.5”
ne
T:11”
CRIBER
INFORMATION
ospital
affiliation
B:11.25”
Facility contact name
25”
license #
#
m is not a prescription.State
Please
complete this form andTax
faxIDdirectly
to Biogen.
1”
Email
City
State
ZIP code
THE FOLLOWING INFORMATION MUST BE FILLED OUT BY YOUR HEALTHCARE
PROVIDER IN ORDER TO RECEIVE
BIOGEN SERVICES.
0.5”
ne
Prescriber signature
Signature stamps not acceptable.
Date
The Prescriber Authorization section is important because you will be
12/22/16 5:00 PM
sharing private information with Biogen as a designated
agent on behalf
of the patient or parent/guardian. It further acknowledges that you are the
prescriber and/or that you will supervise the administration of treatment.
IMPORTANT SAFETY INFORMATION (continued)
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation
for 14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when
administered to infants, as suggested by observations from the
controlled study.
Please see following pages for additional Important Safety Information.
8
START FORM SECTION CHECKLIST
Here is a checklist of the key sections of the SPINRAZA Start Form to be completed
Patient information that is verified by your patients’ parents or guardians
Prescriber information including the physician’s information who will be administering the treatment
Administration plan including date(s) of loading dose(s) and maintenance dose(s)
Facility/site of care/POS, if different than your practice or facility location
M
edical insurance Information should include all insurance information (eg, primary/secondary
insurance) completed as requested
Prescriber authorization with physician signature
If you have any questions about how to fill out the SPINRAZA Start Form, call SMA360° at
1-844-4SPINRAZA (1-844-477-4672), Monday through Friday, 8:30 AM to 8 PM ET, or contact
your Biogen representative.
IMPORTANT SAFETY INFORMATION (continued)
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection (39%
vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse reactions
of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%). Because
patients in the controlled study were infants, adverse reactions that are verbally reported could not be assessed
in this study. In the open-label studies, the most common adverse events in later onset patients were headache
(50%), back pain (41%) and post lumbar puncture syndrome (41%).
Please see following page for additional Important Safety Information.
9
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding
complications. Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at baseline
developed a platelet level below the lower limit of normal compared to zero sham-procedure control patients.
No patient had a platelet count <50,000 cells per mcL and no patient developed a sustained low platelet count
despite continued drug exposure.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some
antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients had
elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA patients, 69%
had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct quantitative
spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose
of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation for
14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as suggested
by observations from the controlled study.
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZA-treated
patients and occurred at least 5% more frequently than in control patients were upper respiratory infection
(39% vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs 22%). Serious adverse
reactions of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control patients (5%).
Because patients in the controlled study were infants, adverse reactions that are verbally reported could not be
assessed in this study. In the open-label studies, the most common adverse events in later onset patients were
headache (50%), back pain (41%) and post lumbar puncture syndrome (41%).
Please see full Prescribing Information for additional Important Safety Information.
10
Please see full Prescribing Information for additional Important Safety Information.
© 2016 Biogen.
All rights reserved.
12/16
SPZ-US-0298
Guide to
Prior Authorization
Submissions
1
and proprietary to Biogen.
Confidential and proprietary toConfidential
Biogen.
Introduction to prior authorizations
In certain instances, your practice or facility may need to obtain prior approval from an insurance
carrier before the insurer will cover a specific drug for a patient. This request for approval is
referred to as prior authorization (PA), precertification, or coverage determination.
PAs are very common for orphan drugs that treat rare diseases, such as spinal muscular
atrophy (SMA), because they enable insurance carriers to monitor costs and ensure that drugs
are being used for appropriate patients only. For many drugs that treat rare diseases, insurance
carriers may require a PA renewal after a certain period (typically 1 year). This is true regardless
of whether the patient is remaining on the same treatment or transitioning to another treatment.
Biogen can help your practice or facility understand the PA
requirements for individual insurance carriers in your area.
Call SMA360°™ at 1-844-4SPINRAZA (1-844-477-4672),
or contact your Biogen representative.
As a reminder, Biogen’s SMA360° support provides certain services that address nonmedical
barriers to access. These include logistical assistance, product education, insurance benefit
investigation, and financial assistance. A complete list of the SMA360° offerings can be found
at www.spinraza-hcp.com/support. SMA360° services from Biogen are available only to those
who have been prescribed SPINRAZA. SMA360° is available only in the US.
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have
been observed after administration of some antisense oligonucleotides. Patients may be at increased
risk of bleeding complications. Perform a platelet count and coagulation laboratory testing at baseline
and prior to each administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at
baseline developed a platelet level below the lower limit of normal compared to zero sham-procedure
control patients. No patient had a platelet count <50,000 cells per mcL and no patient developed a
sustained low platelet count despite continued drug exposure.
Please see page 12 for additional Important Safety Information.
Confidential and proprietary to Biogen.
2
Prior Authorization vs Medical Exception
In situations when a drug is not on an insurance carrier’s
formulary, the physician may still prescribe it if he or she
requests a medical exception, or ME. These requests
are typically more complex than PAs and require specific
documentation, including a letter of medical necessity and
more information about the patient’s medical history.
Guide to Requesting
a Medical Exception
Guide to Requesting
a Medical Exception
For more information about the ME process and its
requirements, refer to the Guide to Requesting a Medical
Exception and the sample Letter of Medical Necessity included in this kit.
Site of care for injected therapies
It is important to determine the insurance carrier’s rules regarding the site of care for injected
drugs. For injected therapies, determine whether the insurance carrier imposes restrictions as
to where it may be administered (eg, the hospital, a separate ambulatory surgical center, or a
physician’s office).
How this guide can help with PA submissions
To help you in understanding the submission process for a PA for a Biogen therapy, this guide will
provide information on
Key steps to
submitting a PA
Fields to complete
on a PA form
Confidential and proprietary to Biogen.
Supporting documentation
that may be required
3
Steps to completing a PA
The following steps illustrate how to complete a PA.
Step 1
Complete the Benefit Investigation.
You will need to first complete a Benefit Investigation to determine whether
your patient has insurance coverage for the prescribed drug. You will need
to find out if there are any restrictions in place, determine if the insurance
carrier has restrictions on where the drug can be administered or which
specialty pharmacy can ship the drug, and identify patient cost-sharing
requirements. Refer to the remaining steps and tips found in this guide to
complete the PA process.
Step 2
Complete the PA form.
Review page 6 to see how supplemental documentation may increase
your PA success.
ake sure you have the proper PA form for that payer. PAs can be denied
M
simply because the wrong form has been submitted
emember to fill out the form completely. PAs are often denied because
R
the form is missing information
Confidential and proprietary to Biogen.
4
Step 3
Submit the PA form.
etermine whether the information should be phoned in, faxed, emailed, or
D
submitted via the website to the insurance carrier. This information is often
listed on the actual form
F or future reference, you may want to add the insurance carrier
contact information, proper submission requirements, and
other tips to the Insurance Carrier Contact Sheet included
in this kit
eep a copy of everything your practice or facility submits with
K
the request. You may need to reference these documents for
many reasons, including if your patient needs financial assistance
services from SMA360° later on
Step 4
Track the status of the PA request.
It is important to keep a thorough log of the PA submissions
and denials for each patient as this information will be needed
if the patient wishes to apply for financial support services
from SMA360°
Step 5
Send additional documentation, if required.
If additional documentation is requested at any point, make
sure to provide it as soon as possible
Did You Know?
The PA process can sometimes take longer than expected.
If you have questions about how long the insurance approval
process is taking, contact your Biogen representative.
Confidential and proprietary to Biogen.
5
Providing supplemental documentation can help to increase
the chance that your patient can start therapy efficiently
Each insurance carrier is unique in its requirements, so it is essential to identify the specific
documents you will need before submitting a PA request. While the preferred forms of
documentation may vary, here is a list of items that may be required with your submission:
Completed PA form (forms vary per insurance carrier)
Relevant literature
Clinical patient notes and relevant patient medical history that substantiates
therapy recommendation
TIP
Make sure to keep copies of all PA request documents
and correspondence for your records.
A successful PA begins with an accurate and
complete form
This sample form is meant to guide you as you complete a PA form. It cannot be submitted.
PA forms vary by insurance carrier and may require more documentation than what is listed on
this sample. Please contact the specific insurance carrier to obtain the correct PA form.
Remember to fill out the insurance carrier’s PA form(s)
properly and completely. Failure to do so could delay your
patient’s treatment.
Confidential and proprietary to Biogen.
6
This is a sample PA form for illustrative purposes only.
How to fill out a PA form
123 Park Ave. • Hometown, IA • 55555
|
Phone: 1-888-555-1234 Fax: 1-888-555-5678
ABC
The first part
of Health
the PA Plan
form (Section A)
is typically where the sender
includes
relevant
For
Medicare Partall
B— Fax:
1-888-555-9191
contact information.
Multiple Sclerosis Therapy Prior Authorization Request Form
All fields must be completed in their entirety and legible.
Section A: Requestor Information
Patient and insurance information
First Name:
Phone:
Last Name:
Fax:
E-mail:
Last Name:
Member ID:
Section B: Patient Information
First Name:
Address:
City:
State:
Zip:
Phone:
DOB:
Allergies:
Is the requested medication NEW
or a CONTINUATION OF THERAPY
?
Start Date:
/
/
Section C: Insurance Information
Member ID #:
Does patient have other coverage?
Group #:
If yes, provide ID#:
Insured:
Yes
No
Carrier Name:
Insured:
Yes
Medicare:
No
If yes, provide ID #:
Medicaid:
Yes
No
If yes, provide ID #:
Section D: Physician Information
Physician Name:
ABC Health Plan
NPI #:
123 Park Ave. • Hometown, IA • 55555
Specialty:
OR MA Provider ID #:
Phone: 1-888-555-1234 Fax: 1-888-555-5678
For Medicare Part B— Fax: 1-888-555-9191
|
State License:
Multiple Sclerosis Therapy Prior Authorization Request Form
All fields must be completed in their entirety and legible.
Section A: Requestor Information
First Name:
Prescriber Address:
City/State/Zip
Suite #:
Phone: (
Last Name:
Phone:
Fax:
Section B: Patient Information
E-mail:
Last Name:
Address:
City:
State:
Phone:
DOB:
Member ID #:
Group #:
Diagnosis (Please be specific & provide as much information as possible):
Zip:
?
Start Date:
/
/
E
L
P
M
SA
Does patient have other coverage?
Comorbidities
Yes
If yes, provide ID #:
Medicaid:
Carrier Name:
Yes
No
Physician Name:
Specialty:
Medication:
OR MA Provider ID #:
NPI #:
Prescriber Address:
City/State/Zip
Phone: (
State License:
Suite #:
)
Directions for use:
Section E: Diagnosis Information
Diagnosis (Please be specific & provide as much information as possible):
Comorbidities
If yes, provide ID #:
Section F: Product Information
Section D: Physician Information
Fax: (
)
ICD-10-CODE:
– Some therapies may be covered under the medical
Section G: Dispensing Provider/Administration
Information
benefit
(ie, the same card you would use to charge
Place of Administration:
Dispensing Provider/Pharmacy: Patient selected choice
Self Administered
Physician’s for
Office the office visit)
Physician’s Office
Retail Pharmacy
Section F: Product Information
Medication:
No
If yes, provide ID#:
No
ICD-10-CODE:
Make sure to include all relevant patient information
and ensure you are using the correct insurance card.
Please note that in some instances,
the patient may
Strength:
have separate medical and pharmacy benefit cards
Allergies:
or a CONTINUATION OF THERAPY
Insured:
Yes
Medicare:
)
Member ID:
Section C: Insurance Information
Insured:
Fax: (
Section E: Diagnosis Information
First Name:
Is the requested medication NEW
)
Strength:
Directions for use:
Section G: Dispensing Provider/Administration Information
Place of Administration:
Self Administered
Outpatient Infusion Center
Center Name:
Home Infusion Center
Agency Name:
Administration code(s) (CPT):
Dispensing Provider/Pharmacy: Patient selected choice
Physician’s Office
Phone:
Phone:
Section H: Clinical Information
Physician’s Office
Specialty Office
Other
Name:
Phone:
TIN:
Retail Pharmacy
Mail Order
Outpatient Infusion Center
Center Name:
Home Infusion Center
Agency Name:
Administration code(s) (CPT):
Fax:
PIN:
Explanation of why the preferred medication(s) would not meet your patient’s needs:
Section I: Patient Treatment History
Medications
Section J: Physician Signature
Physician Signature:
Strength
Phone:
Specialty Office
Other
Name:
Phone:
TIN:
Phone:
Mail Order
Fax:
Make sure to list the patient’s name exactly
as it
PIN:
appears on the insurance card. It is important to
Section H: Clinical Information
Explanation of why the preferred medication(s) would not meet your patient’s needs:
check for possible name changes and make sure
all the documents match
Dates of Therapy
Reason for failure/discontinuation
Date
/
/
Section I: Patient Treatment History
Medications
of Therapy
Reason for failure/discontinuation
Check theDates
appropriate
box to distinguish
between
a new medication and a continuation of therapy
Strength
Section J: Physician Signature
Physician Signature:
Confidential and proprietary to Biogen.
Date
/
/
7
All fields must be completed in their entirety and legible.
Section A: Requestor Information
First Name:
Last Name:
Phone:
Fax:
E-mail:
This is a sample PA form for illustrative purposes only.
Section B: Patient Information
First Name:
Last Name:
Member ID:
Address:
City:
State:
Zip:
Phone:
DOB:
Allergies:
Is the requested medication NEW
or a CONTINUATION OF THERAPY
?
Start Date:
/
/
Prescribing
physician, diagnosis, and product information
Section C: Insurance Information
Member ID #:
Does patient have other coverage?
Group #:
If yes, provide ID#:
Insured:
Yes
No
Carrier Name:
Insured:
Medicare:
Yes
No
If yes, provide ID #:
Medicaid:
Yes
No
If yes, provide ID #:
Section D: Physician Information
Physician Name:
Specialty:
OR MA Provider ID #:
NPI #:
State License:
Prescriber Address:
Suite #:
City/State/Zip
Phone: (
)
Fax: (
)
Section E: Diagnosis Information
Diagnosis (Please be specific & provide as much information as possible):
ICD-10-CODE:
Comorbidities
Section F: Product Information
Medication:
Strength:
Directions for use:
Section G: Dispensing Provider/Administration Information
Place of Administration:
Dispensing Provider/Pharmacy: Patient selected choice
Self Administered
Outpatient
Infusion
Center
Multiple Sclerosis
Therapy Prior
Authorization
Request Form
Center Name:
Section A: Requestor Information
Home Infusion Center
Agency Name:
Section B: Patient Information
Administration code(s) (CPT):
ABC Health Plan
123 Park Ave. • Hometown, IA • 55555
Physician’s Office
Phone:
Phone: 1-888-555-1234 Fax: 1-888-555-5678
For Medicare Part B— Fax: 1-888-555-9191
|
All fields must be completed in their entirety and legible.
First Name:
Last Name:
Phone:
Fax:
E-mail:
First Name:
Last Name:
Member ID:
Address:
Phone:
Section H: Clinical Information
City:
State:
Phone:
Member ID #:
Allergies:
?
Start Date:
/
Complete the physician information section.
Be sure to include all identification and/or
licensing information
/
E
L
P
M
A
S
Yes
Does patient have other coverage?
If yes, provide ID#:
No
Carrier Name:
Insured:
Yes
Medicare:
No
If yes, provide ID #:
Medicaid:
Yes
No
If yes, provide ID #:
Section D: Physician Information
Physician Name:
Specialty:
Section I: Patient Treatment History
OR MA Provider ID #:
NPI #:
Prescriber Address:
City/State/Zip
State License:
Suite #:
Phone: (
Medications
)
Fax: (
Section E: Diagnosis Information
Diagnosis (Please be specific & provide as much information as possible):
Comorbidities
)
Strength
Strength:
Directions for use:
Section G: Dispensing Provider/Administration Information
Place of Administration:
Self Administered
Outpatient Infusion Center
Center Name:
Home Infusion Center
Agency Name:
Administration code(s) (CPT):
Dispensing Provider/Pharmacy: Patient selected choice
Physician’s Office
Phone:
Section H: Clinical Information
Physician’s Office
Specialty Office
Other
Name:
Phone:
TIN:
Retail Pharmacy
Mail Order
Section J: Physician Signature
Phone:
Fax:
PIN:
Physician Signature:
Explanation of why the preferred medication(s) would not meet your patient’s needs:
Section I: Patient Treatment History
Medications
Strength
Dates of Therapy
Reason for failure/discontinuation
Provide a detailed diagnosis and ICD-10 code so
the insurance carrier understands why a medication
is being requested. Ensure the ICD-10 code and the
language used to describe
matches
Date the /diagnosis
/
the FDA-approved indications for the drug
Reason for failure/discontinuation
Section J: Physician Signature
Physician Signature:
Dates of Therapy
ICD-10-CODE:
Section F: Product Information
Medication:
Fax:
PIN:
Explanation of why the preferred medication(s) would not meet your patient’s needs:
or a CONTINUATION OF THERAPY
Section C: Insurance Information
Group #:
Insured:
Retail Pharmacy
Mail Order
Zip:
DOB:
Is the requested medication NEW
Physician’s Office
Specialty Office
Other
Name:
Phone:
TIN:
Date
/
/
It is important to list any comorbidities, as this may
help provide medical rationale for the prescribed
medication vs an alternate medication
Include the name and dosage of the medication
you want to prescribe for your patient
FDA=US Food and Drug Administration; ICD-10=International Classification of Diseases, Tenth Revision.
Confidential and proprietary to Biogen.
8
Medicare:
Yes
No
If yes, provide ID #:
Medicaid:
Yes
No
If yes, provide ID #:
Section D: Physician Information
Physician Name:
Specialty:
OR MA Provider ID #:
NPI #:
Prescriber Address:
City/State/Zip
Phone: (
State License:
This is a sample PA form
Suite #: for illustrative purposes only.
)
Fax: (
)
Section E: Diagnosis Information
Diagnosis (Please be specific & provide as much information as possible):
ICD-10-CODE:
Comorbidities
Place ofSection
administration,
dispensing provider/pharmacy,
F: Product Information
and clinical information
Medication:
Strength:
Directions for use:
Section G: Dispensing Provider/Administration Information
Place of Administration:
Dispensing Provider/Pharmacy: Patient selected choice
Self Administered
Outpatient Infusion Center
Center Name:
Home Infusion Center
Agency Name:
Administration code(s) (CPT):
Physician’s Office
Phone:
Phone:
Physician’s Office
Specialty Office
Other
Name:
Phone:
TIN:
Retail Pharmacy
Mail Order
Fax:
PIN:
Section H: Clinical Information
Explanation of why the preferred medication(s) would not meet your patient’s needs:
Section I: Patient Treatment History
ABC Health Plan
123 Park Ave. • Hometown, IA • 55555
Phone: 1-888-555-1234 Fax: 1-888-555-5678
For Medicare Part B— Fax: 1-888-555-9191
|
Multiple Sclerosis Therapy Prior Authorization Request Form
Medications
All fields must be completed in their entirety and legible.
Strength
Dates of Therapy
Reason for failure/discontinuation
Section A: Requestor Information
First Name:
Last Name:
Phone:
Fax:
E-mail:
Section B: Patient Information
First Name:
Last Name:
Member ID:
Address:
City:
State:
Zip:
Phone:
DOB:
Allergies:
Is the requested medication NEW
or a CONTINUATION OF THERAPY
?
Start Date:
/
/
E
L
P
M
A
S
Section C: Insurance Information
Member ID #:
Yes
Does patient have other coverage?
No
Section J: Physician Signature
Group #:
If yes, provide ID#:
Insured:
Carrier Name:
Insured:
Yes
Medicare:
No
If yes, provide ID #:
Yes
Physician Signature:
Section D: Physician Information
Physician Name:
Medicaid:
Suite #:
Phone: (
)
Fax: (
)
Section E: Diagnosis Information
Diagnosis (Please be specific & provide as much information as possible):
Comorbidities
ICD-10-CODE:
Section F: Product Information
Medication:
Date
/
/
State License:
Prescriber Address:
City/State/Zip
If yes, provide ID #:
Specialty:
OR MA Provider ID #:
NPI #:
No
T he Place of Administration is the site of care. If your
site of care is not listed, you should write it in
Strength:
Directions for use:
Section G: Dispensing Provider/Administration Information
Place of Administration:
Self Administered
Outpatient Infusion Center
Center Name:
Home Infusion Center
Agency Name:
Administration code(s) (CPT):
Dispensing Provider/Pharmacy: Patient selected choice
Physician’s Office
Phone:
Phone:
Physician’s Office
Specialty Office
Other
Name:
Phone:
TIN:
Retail Pharmacy
Mail Order
Fax:
PIN:
Section H: Clinical Information
Explanation of why the preferred medication(s) would not meet your patient’s needs:
Section I: Patient Treatment History
Medications
Strength
Dates of Therapy
Reason for failure/discontinuation
F or the Dispensing Provider/Pharmacy section, make
sure to use the information found from the Benefit
Investigation to ensure you are listing a specialty
pharmacy that is in-network
Section J: Physician Signature
Physician Signature:
Date
/
/
If the prescribed medication is not Preferred or Not
Covered on the insurance carrier’s formulary, provide
a detailed explanation describing why the preferred
formulary medications are not appropriate for your patient.
Use the sample Letter of Medical Necessity template
included in this kit to help with your explanation. You may
need to provide additional documentation, such as
medical literature and the patient’s medical history
Confidential and proprietary to Biogen.
9
Prescriber Address:
Suite #:
City/State/Zip
Phone: (
)
Fax: (
)
Section E: Diagnosis Information
Diagnosis (Please be specific & provide as much information as possible):
ICD-10-CODE:
This is a sample PA form for illustrative purposes only.
Comorbidities
Section F: Product Information
Medication:
Strength:
Directions for use:
Patient treatment history and physician signature
Section G: Dispensing Provider/Administration Information
List any medications the patient has used
for treatment. If there are no prior
Dispensing Provider/Pharmacy: Patient selected choice
Self Administered
Physician’s Office
Physician’s Office
Retail Pharmacy
treatments, write Phone:
“none.”
Review the patient’s
Benefit Investigation.
If the request is
Outpatient Infusion Center
Specialty Office
Mail Order
Center Name:
Other
of the insurance
carrier’s policy, aName:
letter of medical necessity may be required
Phone:
Homeoutside
Infusion Center
Place of Administration:
Agency Name:
Administration code(s) (CPT):
Phone:
TIN:
Fax:
PIN:
Section H: Clinical Information
Ensure that you sign all documentation where required
Explanation of why the preferred medication(s) would not meet your patient’s needs:
Section I: Patient Treatment History
Medications
Strength
Dates of Therapy
Reason for failure/discontinuation
Section J: Physician Signature
Physician Signature:
ABC Health Plan
Date
123 Park Ave. • Hometown, IA • 55555
/
/
Phone: 1-888-555-1234 Fax: 1-888-555-5678
For Medicare Part B— Fax: 1-888-555-9191
|
Multiple Sclerosis Therapy Prior Authorization Request Form
All fields must be completed in their entirety and legible.
Section A: Requestor Information
First Name:
Last Name:
Phone:
Fax:
E-mail:
Section B: Patient Information
First Name:
Last Name:
Member ID:
Address:
City:
State:
Zip:
Phone:
DOB:
Allergies:
E
L
P
M
A
S
Is the requested medication NEW
or a CONTINUATION OF THERAPY
?
Start Date:
/
/
Section C: Insurance Information
Member ID #:
Group #:
Does patient have other coverage?
Yes
If yes, provide ID#:
Insured:
No
Carrier Name:
Insured:
Yes
Medicare:
No
If yes, provide ID #:
Medicaid:
Yes
No
If yes, provide ID #:
Section D: Physician Information
Physician Name:
Specialty:
OR MA Provider ID #:
NPI #:
State License:
Prescriber Address:
City/State/Zip
Suite #:
Phone: (
)
Fax: (
)
Section E: Diagnosis Information
Diagnosis (Please be specific & provide as much information as possible):
Comorbidities
ICD-10-CODE:
Section F: Product Information
Medication:
Strength:
Directions for use:
Section G: Dispensing Provider/Administration Information
Place of Administration:
Self Administered
Outpatient Infusion Center
Center Name:
Home Infusion Center
Agency Name:
Administration code(s) (CPT):
Dispensing Provider/Pharmacy: Patient selected choice
Physician’s Office
Phone:
Phone:
Physician’s Office
Specialty Office
Other
Name:
Phone:
TIN:
Retail Pharmacy
Mail Order
Fax:
PIN:
Section H: Clinical Information
Explanation of why the preferred medication(s) would not meet your patient’s needs:
Section I: Patient Treatment History
Medications
Strength
Dates of Therapy
Reason for failure/discontinuation
Section J: Physician Signature
Physician Signature:
Date
/
/
Submission of improperly completed or incomplete forms
is the primary reason denials occur. Make sure to read and
complete the PA form carefully before submitting.
Confidential and proprietary to Biogen.
10
In the case of a denial
There are many reasons why an authorization may be denied. One of the main reasons PA
requests are denied is incomplete or inaccurate information on the PA form. Check to ensure
all information is complete and accurate. Resubmit the form if necessary.
In some cases, a letter of medical necessity may be required when the PA is being resubmitted.
Review the sample Letter of Medical Necessity template included in this kit.
In the event that the PA request has been denied, the physician can appeal the decision
by contacting the insurance carrier directly to have a peer-to-peer discussion regarding the
patient, the clinical issues, and the reasons for requesting a specific drug. If a phone call is
not possible, you may submit an ME request.
Insurance Carrier Contact Sheet
The Insurance Carrier Contact Sheet resource will enable you to capture key contact information and related processes for payers.
Insurance Carrier
Name
Phone
Email
For infusible products, please see the Payer Summary Reference Guide resource available from Biogen.
Contact
Role
Dept.
Additional Notes
Preference for PA and/or ME Submissions
Phone
Fax
Email
Other
Relevant Web Links
ME=medical exception; PA=prior authorization.
If you work with a specific individual at the insurance
carrier to handle denials of PA requests, you may
want to include that individual’s contact information
on the Insurance Carrier Contact Sheet in this kit for
future reference
Biogen can help your practice or facility understand the PA
requirements for individual insurance carriers in your area.
Call SMA360°™ at 1-844-4SPINRAZA (1-844-477-4672),
or contact your Biogen representative.
Please see the following page for additional Important Safety Information.
Confidential and proprietary to Biogen.
11
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have
been observed after administration of some antisense oligonucleotides. Patients may be at increased
risk of bleeding complications. Perform a platelet count and coagulation laboratory testing at baseline
and prior to each administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at
baseline developed a platelet level below the lower limit of normal compared to zero sham-procedure
control patients. No patient had a platelet count <50,000 cells per mcL and no patient developed a
sustained low platelet count despite continued drug exposure.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of
some antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients
had elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA
patients, 69% had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct
quantitative spot urine protein testing (preferably using a first morning urine specimen) at baseline
and prior to each dose of SPINRAZA. For urinary protein concentration >0.2 g/L, consider
repeat testing and further evaluation.
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation
for 14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as
suggested by observations from the controlled study.
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZAtreated patients and occurred at least 5% more frequently than in control patients were upper
respiratory infection (39% vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs
22%). Serious adverse reactions of atelectasis were more frequent in SPINRAZA-treated patients (14%)
than in control patients (5%). Because patients in the controlled study were infants, adverse reactions
that are verbally reported could not be assessed in this study. In the open-label studies, the most
common adverse events in later onset patients were headache (50%), back pain (41%) and post lumbar
puncture syndrome (41%).
Please see full Prescribing Information for additional Important Safety Information.
Confidential and proprietary to Biogen.
© 2016 Biogen.
Confidential and proprietary to Biogen.
All rights reserved.
12/16
SPZ-US-0299
12
Guide to Requesting
a Medical Exception
Confidential and proprietary to Biogen.
1
Reviewing the steps to a medical exception approval
There are occasions when a treatment is not on an insurance carrier’s formulary but the
physician can still prescribe it. This request for approval is called a medical exception (ME).
A medical exception communicates a physician’s request to use medication due to the patient’s
individual circumstances that is nonpreferred or not covered by the insurance carrier.
This guide provides information and considerations for preparing a comprehensive
ME package—from submitting the ME request and additional documentation to
tracking the process.
Steps to completing a medical exception —
Benefit Investigation
Complete a Benefit Investigation.
STEP 1
Know what will be required for your patient to receive treatment,
such as
–If there is a prior authorization or other restrictions in place
Guide to Prior
Authorization Submissions
Guide to
Prior Authorization
Submissions
• If you have a prior authorization, refer to the Guide to
Prior Authorization Submissions resource in this kit
– The patient’s medical history and any related documentation
– If there are restrictions around where the treatment can be administered
–The patient’s copay, co-insurance, or other out-of-pocket costs
Insurance Carrier Contact Sheet
The Insurance Carrier Contact Sheet resource will enable you to capture key contact information and related processes for payers.
Insurance Carrier
Name
Phone
Email
Contact
Role
Dept.
Additional Notes
Preference for PA and/or ME Submissions
Phone
Fax
Email
Other
Relevant Web Links
Consider recording contact information for health plans in the Insurance
Carrier Contact Sheet on the flash drive in this kit for future reference
For infusible products, please see the Payer Summary Reference Guide resource available from Biogen.
ME=medical exception; PA=prior authorization.
Confidential and proprietary to Biogen.
2
Steps to completing a medical exception —
letter of medical necessity
Complete the medical exception request with
a letter of medical necessity, as needed.
STEP 2
Completing the ME request may include a form from the insurance carrier or a separate letter
from your office
A common reason that MEs are denied is because there is missing
or incorrect information on the form. This may delay treatment for
your patient. Remember to carefully and accurately complete the
ME request form.
TEMPLATE
Letter of Medical Necessity
The Use of SPINRAZA™ (nusinersen) for
Spinal Muscular Atrophy
E
L
P
M
Date:
[Insert Name of Medical Director]
[Insurance Company]
[Address]
RE: Patient Name [
Policy Number [
Claim Number [
]
]
]
SA
[City, State, Zip]
Dear [Insurance Company]:
I am writing this letter of medical necessity to provide information related to the
treatment of [insert patient name] with SPINRAZA™ (nusinersen), the only US Food
and Drug Administration (FDA)–approved treatment for spinal muscular atrophy (SMA).
Provide any additional information and documentation. Use the sample
Letter of Medical Necessity on the flash drive in this kit for support and
information you may want to include with the ME request
I would like to provide the following information about the potential benefits of
SPINRAZA in patients with SMA:
1. SMA Pathophysiology
SMA is a genetic neuromuscular disease characterized by degeneration of
motor neurons in the anterior horn of the spinal cord. SMA is characterized by
progressive symmetrical weakness and atrophy of the proximal voluntary muscles of
legs, arms, and eventually of the entire trunk during disease progression. Infants and
SPZ-US-0309 12/16
Refer to the SPINRAZA™ (nusinersen) Clinical Overview in this kit for
efficacy and safety information to include in your letter of medical necessity
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk
of bleeding complications. Perform a platelet count and coagulation laboratory testing at baseline and
prior to each administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at
baseline developed a platelet level below the lower limit of normal compared to zero sham-procedure
control patients. No patient had a platelet count <50,000 cells per mcL and no patient developed a
sustained low platelet count despite continued drug exposure.
Please see page 7 for additional Important Safety Information.
Confidential and proprietary to Biogen.
3
An effective letter of medical necessity is tailored to your patient’s needs
Be clear about your patient’s individual circumstance. The following are key considerations when
writing a letter of medical necessity.
Provide a background on your patient’s condition
Summarize his or her clinical status citing diagnostic evidence of spinal muscular atrophy (SMA),
including genetic testing
If appropriate, list current supportive care management, and provide clinical
evidence of the patient’s inadequate response
Explain why the treatment you recommend is, in your opinion, the appropriate choice
for your patient
Provide a clinical justification supporting the treatment you have chosen for
your patient
State any patient-specific reasons for the treatment choice, such as efficacy
Cite relevant literature
Providing additional documentation that supports your decision may strengthen
your request
Details from the patient’s medical record
If appropriate, general medical history listing comorbidities and any
medication history
Other relevant patient information may also be included, as appropriate
Other documentation
Letters from consultants or other healthcare professionals that
support your treatment choice
Clinical information regarding your treatment choice, such as the
product prescribing information
Confidential and proprietary to Biogen.
4
Steps to completing a medical exception—
submission and tracking
Determine how to submit the medical exception.
STEP 3
Insurance Carrier Contact Sheet
The Insurance Carrier Contact Sheet resource will enable you to capture key contact information and related processes for payers.
Insurance Carrier
Name
Phone
Email
Contact
Role
Dept.
Additional Notes
Preference for PA and/or ME Submissions
Phone
Fax
Email
Other
Relevant Web Links
Determine whether the ME needs to be phoned in, faxed, emailed,
or submitted via website to the insurance carrier
Determine the appropriate individual to contact regarding the
medical exception request
For infusible products, please see the Payer Summary Reference Guide resource available from Biogen.
ME=medical exception; PA=prior authorization.
Consider updating the Insurance Carrier Contact Sheet with
specific information related to submitting an ME for the individual
insurance carrier, such as submission format (fax or email). This
is included with this kit
Some states have legislation that requires insurance carriers to
respond to medical exception requests within a certain period of
time. Contact your Biogen representative to learn whether this
applies in your state.
Confidential and proprietary to Biogen.
5
If the medical exception is denied
There are many reasons why an ME may be denied. The most common reason is that there
is inaccurate or incomplete information on the request. Carefully review the request to ensure
that the information is correct and that no information has been omitted. Resubmit the request if
necessary. Your Biogen representative can help you understand the process for handling an ME
denial. Make sure to provide the denial number so he or she can help more quickly.
If all information was complete but the ME was denied due to clinical reasons, the prescribing
physician in your office may also contact the insurance carrier directly to speak with a clinical
representative. This individual is typically someone with a medical background and may be called a
Medical Director. A peer-to-peer discussion regarding the patient can take place that includes more
detailed information about the patient’s medical history and clinical considerations as well as the
reason for the requested treatment. This discussion may help the insurance carrier understand the
concerns for your patient and why there is an ME request for your treatment of choice.
If the healthcare provider is able to obtain the direct contact information for the clinical
representative for future peer-to-peer discussion, consider tracking that information in the
Insurance Carrier Contact Sheet.
If you have questions about the ME process for a Biogen product, call
SMA 360°™ at 1-844-4SPINRAZA (1-844-477-4672), Monday through
Friday, 8:30 AM to 8 PM ET, or contact your Biogen representative.
As a reminder, Biogen’s SMA360° support provides certain services that address nonmedical
barriers to access. These include logistical assistance, product education, insurance benefit
investigation, and financial assistance. A complete list of the SMA360° offerings can be found at
www.spinraza-hcp.com/support. SMA360° services from Biogen are available only to those who
have been prescribed SPINRAZA. SMA360° is available only in the US.
Please see following page for additional Important Safety Information.
Confidential and proprietary to Biogen.
6
INDICATION
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
IMPORTANT SAFETY INFORMATION
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been
observed after administration of some antisense oligonucleotides. Patients may be at increased risk
of bleeding complications. Perform a platelet count and coagulation laboratory testing at baseline and
prior to each administration of SPINRAZA and as clinically needed.
In a clinical study, 11% of SPINRAZA-treated patients with normal or above normal platelet levels at
baseline developed a platelet level below the lower limit of normal compared to zero sham-procedure
control patients. No patient had a platelet count <50,000 cells per mcL and no patient developed a
sustained low platelet count despite continued drug exposure.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of
some antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study, 33% of SPINRAZA-treated patients
had elevated urine protein, compared to 20% of sham-control patients. In a group of later-onset SMA
patients, 69% had elevated urine protein.
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. Conduct
quantitative spot urine protein testing (preferably using a first morning urine specimen) at baseline
and prior to each dose of SPINRAZA. For urinary protein concentration >0.2 g/L, consider
repeat testing and further evaluation.
Severe hyponatremia was reported in an infant treated with SPINRAZA requiring salt supplementation
for 14 months.
Cases of rash were reported in patients treated with SPINRAZA.
SPINRAZA may cause a reduction in growth as measured by height when administered to infants, as
suggested by observations from the controlled study.
The most common adverse reactions that occurred in the controlled study in at least 20% of SPINRAZAtreated patients and occurred at least 5% more frequently than in control patients were upper
respiratory infection (39% vs 34%), lower respiratory infection (43% vs 29%), and constipation (30% vs
22%). Serious adverse reactions of atelectasis were more frequent in SPINRAZA-treated patients (14%)
than in control patients (5%). Because patients in the controlled study were infants, adverse reactions
that are verbally reported could not be assessed in this study. In the open-label studies, the most
common adverse events in later onset patients were headache (50%), back pain (41%) and post lumbar
puncture syndrome (41%).
Please see full Prescribing Information for additional Important Safety Information.
Confidential and proprietary to Biogen.
© 2016 Biogen.
Confidential and proprietary to Biogen.
All rights reserved.
12/16
SPZ-US-0300
7
TEMPLATE
Letter of Medical Necessity
The Use of SPINRAZA™ (nusinersen) for
Spinal Muscular Atrophy Date:
[Insert Name of Medical Director]
RE: Patient Name [
]
[Insurance Company]
Policy Number [
]
[Address]
Claim Number [
]
[City, State, Zip]
Dear [Insurance Company]:
I am writing this letter of medical necessity to provide information related to the
treatment of [insert patient name] with SPINRAZA™ (nusinersen), the only US Food
and Drug Administration (FDA)–approved treatment for spinal muscular atrophy (SMA).
I would like to provide the following information about the potential benefits of
SPINRAZA in patients with SMA:
1. SMA Pathophysiology
SMA is a genetic neuromuscular disease characterized by degeneration of
motor neurons in the anterior horn of the spinal cord. SMA is characterized by
progressive symmetrical weakness and atrophy of the proximal voluntary muscles of
legs, arms, and eventually of the entire trunk during disease progression. Infants and
children affected by SMA develop profound deficits in motor function and miss several
12/16
developmental milestones. SMA is among the leading genetic causes of infant
mortality.
2. About SPINRAZA
SPINRAZA is the first and only treatment approved by the FDA indicated for SMA in
pediatric and adult patients. SPINRAZA has been studied across multiple clinical trials in
patients with varying types of SMA, including presymptomatic and symptomatic infantileonset and later-onset SMA. The patients in these studies had or were likely to develop Type
1, 2, or 3 SMA. The overall findings of the controlled trial in infantile-onset SMA and the
open-label uncontrolled trials support the effectiveness of SPINRAZA across the range of
patients with SMA and appear to support the early initiation of treatment with SPINRAZA. 3. Rationale for Treatment
[Note: Exercise your medical judgment and discretion when providing a
diagnosis and characterization of the patient’s medical conditions.]
In brief, based on the clinical data available to date, it is my medical opinion that
initiating treatment of [patient name] with SPINRAZA is medically appropriate and
necessary and the procedures required for its administration should be a covered and
reimbursed service. Below, this letter outlines [patient name’s] medical history,
prognoses, and the rationale for treatment with SPINRAZA (to be completed by
physician based on patient medical history and prognosis).
4. Summary of Patient’s History [You may want to include]:
• Patient’s diagnosis, condition, and history
• Previous therapies the patient has undergone for the symptoms associated with their
condition
• Patient’s response to these therapies
• Brief description of the patient’s recent symptoms and conditions
5. Patient’s Prognosis
•
Summary of your professional opinion of the patient’s likely prognosis without
SPINRAZA treatment
12/16
6. Dosing Schedule
SPINRAZA is administered by, or under the direction of, healthcare
professionals experienced in performing lumbar punctures. Treatment begins with 4
loading doses; the first 3 loading doses should be administered at 14-day intervals,
and the fourth loading dose should be administered 30 days after the third dose.
A maintenance dose is administered once every 4 months thereafter.
Approximate Dosing Regimen Illustration
Conduct the following laboratory tests at baseline and prior to each dose of
SPINRAZA and as clinically needed:

Platelet count

Prothrombin time; activated partial thromboplastin time

Quantitative spot urine protein testing
7. Administration of SPINRAZA
In clinical trials, SPINRAZA has been administered in a hospital outpatient
setting by or under the direction of a healthcare professional with experience in the
lumbar puncture procedure. Administration of SPINRAZA may require additional
medical procedures including sedation/anesthesia and/or imaging to aid in the lumbar
puncture (eg, ultrasound).
[Insert more detail lower in the letter when discussing individual patient needs
as appropriate; fill in relevant services with rationale about why the services are
clinically appropriate for each patient].
8. SPINRAZA Clinical Trial Program
The efficacy of SPINRAZA was demonstrated in a double-blind, shamprocedure controlled phase 3 clinical trial (ENDEAR) in 121 symptomatic infantileonset patients with SMA (symptom onset before 6 months of age). Patients were aged
≤7 months at the time of first dose, and 98% of patients had 2 copies of the SMN2
gene, mostly consistent with a clinical diagnosis of Type 1 SMA. The efficacy of
12/16
SPINRAZA was also supported by open-label clinical trials conducted in patients with
presymptomatic and symptomatic infantile SMA as well as later-onset SMA. The
patients in these studies had or were likely to develop Type 1, 2, or 3 SMA.
9. Summary of Clinical Trials for SPINRAZA
Information about the following clinical trials for SPINRAZA is available on
clinicaltrials.gov.
Study
ENDEAR
(NCT02193074)
CHERISH
(NCT02292537)
Phase
Description
3
Randomized, sham-controlled trial in infants with SMA
3
Randomized, sham-controlled trial in children with
SMA
Status
Positive
Interim
Results*
Positive
Interim
Results*
Supporting Open-Label Studies
SHINE
(NCT02594124)
EMBRACE
(NCT02462759)
NURTURE
(NCT02386553)
CS3A
(NCT01839656)
CS12
(NCT02052791)
CS10
(NCT01780246)
CS2
(NCT01703988)
CS1
(NCT01494701)
3
Open-label extension for participants in ENDEAR and
CHERISH studies
On-going
2
Open-label, multi-dose trial in infants and children who did
not qualify for ENDEAR or CHERISH
On-going
2
Open-label study in genetically diagnosed pre-symptomatic
infants with SMA
On-going
2
Open-label, multi-dose trial in infants with SMA to assess
tolerability and pharmacokinetics
Completed
2
Open-label safety and tolerability study in patients with SMA
who previously participated in the CS2 or CS10 studies
Completed
1
Open-label safety and tolerability study in patients with SMA
who previously participated in the CS1 study
Completed
1
Open-label safety, tolerability and dose-range finding study
of multiple doses in patient with spinal muscular atrophy
Completed
1
Open-label safety, tolerability, and dose-range finding study
in patients with SMA
Completed
*Study stopped based on positive pre-specified interim analysis
12/16
10. Top Level Interim Efficacy Data From ENDEAR and Supportive Open-Label
Studies
In the interim analysis of the controlled, Phase 3 ENDEAR study in infantile-onset
SMA, infants treated with SPINRAZA demonstrated a statistically and clinically significant
improvement in the primary endpoint (P<0.0001), defined as the proportion of motor
milestone responders as measured by the Hammersmith Infant Neurological Examination
(HINE) Section 2. This endpoint evaluates 7 different areas of motor milestone development,
with a maximum score between 2 and 4 points for each, depending on the milestone, and a
total maximum score of 26. A treatment responder was defined as any patient with at least a
2-point increase (or maximal score of 4) in the ability to kick (consistent with improvement by
at least 2 milestones), or at least a 1-point increase in the motor milestones of head control,
rolling, sitting, crawling, standing, or walking (consistent with improvement by at least 1
milestone). To be classified as a responder, patients needed to exhibit improvement in more
categories of motor milestones than worsening. Although not statistically controlled for
multiple comparisons at the interim analysis, the study also assessed treatment effects on
the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP
INTEND), which is an evaluation of motor skills in patients with infantile-onset SMA.
Supportive Open-Label Studies
The results of the controlled trial in infantile-onset patients with SMA (ENDEAR) were
supported by open-label uncontrolled trials conducted in symptomatic patients with SMA
(infantile onset and later onset) who ranged in age from 30 days to 15 years at the time of
first dose, and in presymptomatic patients with SMA (infantile onset), who ranged in age
from 8 days to 42 days at the time of first dose. The patients in these studies had or were
likely to develop Type 1, 2, or 3 SMA. Some patients achieved milestones such as ability to
sit unassisted, stand, or walk when they would otherwise be unexpected to do so,
maintained milestones at ages when they would be expected to be lost, and survived to ages
unexpected, considering the number of SMN2 gene copies of patients enrolled in the
studies.
11. Safety Results for ENDEAR and Supportive Open-Label Studies
Coagulation abnormalities and thrombocytopenia, including acute severe
thrombocytopenia, have been observed after administration of some antisense
oligonucleotides. Because of the risk of thrombocytopenia and coagulation
12/16
abnormalities from SPINRAZA, patients may be at increased risk of bleeding
complications.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed
after administration of some antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney. In a clinical study (mean
treatment exposure 7 months), 17 of 51 (33%) SPINRAZA-treated patients had
elevated urine protein, compared to 5 of 25 (20%) sham-control patients.
The most common adverse reactions that occurred in at least 20% of
SPINRAZA-treated patients and occurred at least 5% more frequently than in control
patients in ENDEAR were lower respiratory infection, upper respiratory infection, and
constipation. Serious adverse reactions of atelectasis were more frequent in
SPINRAZA-treated patients (14%) than in control patients (5%). Because patients in
the controlled study were infants, adverse reactions that are verbally reported could
not be assessed in this study.
In an open-label clinical study in infants with symptomatic SMA, severe
hyponatremia was reported in a patient treated with SPINRAZA requiring salt
supplementation for 14 months.
The most common adverse events in the open-label studies in later-onset
patients were headache (50%), back pain (41%) and post lumbar puncture syndrome
(41%). Most of these events occurred within 5 days of lumbar puncture. Other adverse
events in these patients were consistent with adverse reactions observed in the
controlled study.
Adverse reactions that occurred in at least 5% of patients treated with
SPINRAZA and occurred at least 5% more frequently, or at least 2 times as frequently
than in control patients, in the controlled study in infants with symptomatic SMA
included

Lower respiratory infection

Upper respiratory infection

Constipation

Teething

Upper respiratory tract congestion

Aspiration

Ear infection

Scoliosis
12/16
12. Concluding Remarks
[HCP to insert information relevant to particular case (eg, Given the patient’s
history, his/her current condition, lack of treatment options for SMA and the emerging
data of the effects of SPINRAZA in patients with SMA, I believe treatment of [insert
patient name] with this product is warranted, appropriate, and medically necessary.
The totality of the data available to date support the potential benefit of treatment with
SPINRAZA).]
Please call my office at [insert telephone number] if I can provide you with any
additional information. I look forward to receiving your timely response and approval of this
claim.
Sincerely,
[Insert Doctor name and
Participating provider number]
13. References
1. Prior TW. Spinal muscular atrophy: a time for screening. Curr Opin Pediatr.
2010; 22(6):696-702.
2. Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal
muscular atrophy type I and implications for clinical trials. Neurology.
2014;83(9):810-817.
3. Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of
nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology.
2016;86(10):890-897.
4. Haché M, Swoboda KJ, Sethna N, et al. Intrathecal injections in children with
spinal muscular atrophy: nusinersen clinical trial experience. J Child Neurol.
2016;31(7):899-906.
12/16
5. Finkel RS, Chiriboga CA, Vajsar J, et al. Interim results of a phase 2 clinical
study of nusinersen in patients with infantile-onset spinal muscular atrophy.
Lancet. 2016;688(10063):3017-3026.
6. Darras BT, Chiriboga CA, Montes J, et al. Nusinersen in treatment-naive
patients with later-onset spinal muscular atrophy (SMA): efficacy results from a
phase 1b/2a multicentre study (CS2) and its open-label extension (CS12).
World Muscle Society Meeting, Granada Spain, October 2016.
7. Bertini E, Hwu W-L, Reyna SP, et al. Nusinersen in pre-symptomatic infants
with spinal muscular atrophy (SMA): interim efficacy and safety results from the
phase 2 nurture study. World Muscle Society Meeting, Granada Spain, October
2016.
8. Kuntz N, Farwell W, Zhong ZJ, et al. Nusinersen treatment of infantile-onset
spinal muscular atrophy (SMA): study design and initial interim efficacy and
safety findings from the phase 3 ENDEAR study. World Muscle Society
Meeting, Granada Spain, October 2016.
9. SPINRAZA [Prescribing Information]. Cambridge, MA: Biogen; December 2016.
12/16
Insurance Carrier Contact Sheet
The Insurance Carrier Contact Sheet resource will enable you to capture key contact information and related processes for payers.
Insurance Carrier
Name
Phone
Email
Contact
Role
Dept.
Additional Notes
Preference for PA and/or ME Submissions
Phone
Fax
Email
Other
Relevant Web Links
ME=medical exception; PA=prior authorization.
Insurance Carrier Contact Sheet
The Insurance Carrier Contact Sheet resource will enable you to capture key contact information and related processes for payers.
Insurance Carrier
Name
Phone
Email
Contact
Role
Dept.
Additional Notes
Preference for PA and/or ME Submissions
Phone
Fax
Email
Other
Relevant Web Links
ME=medical exception; PA=prior authorization.
Insurance Carrier Contact Sheet
The Insurance Carrier Contact Sheet resource will enable you to capture key contact information and related processes for payers.
Insurance Carrier
© 2016 Biogen.
Name
All rights reserved.
Phone
12/16
Email
SMA-US-0183
Contact
Role
Dept.
Additional Notes
Preference for PA and/or ME Submissions
Phone
Fax
Email
Other
Relevant Web Links
ME=medical exception; PA=prior authorization.
UNDERSTANDING MEDICAL BENEFIT AND
PHARMACY BENEFIT INSURANCE CARDS
Knowing which insurance card to use on Biogen patient start forms may
help patients receive Biogen support services quickly
If you are prescribing a specialty drug, you may be required to fill out a Biogen patient start form to allow your
patients to access services. Correctly completing the patient insurance information on the form can help
ensure the request is processed by the specialty distributor/pharmacy and the insurance company in a timely
manner so that patients can receive Biogen support services more quickly. It’s important to know that prior
authorizations may be denied due to incomplete or insufficient prescription information, not because the patient
does not have coverage for the drug.
A specialty drug may be covered by a medical or a pharmacy benefit,
depending on the type of medication and how it’s administered1
edical benefits generally cover drugs that are injected or infused by a healthcare professional in the
M
doctor’s office, infusion center, or hospital outpatient center
P
harmacy benefits generally cover drugs that are self-administered orally, by injection, or inhaled
1 card vs 2 cards
Pharmacy vs medical benefits can be determined based on the insurance cards. Here’s how:
card for both medical and pharmacy benefits. Health plans may combine the medical and pharmacy
1
benefit into 1 program. The patient will have 1 insurance card that includes member identification information
(eg, group number and member “ID”) for both the medical and pharmacy benefit. The card may also include
copay or coinsurance costs for doctor office, specialist, and emergency room (ER) visits. Insurance cards for
both benefits typically note the pharmacy benefit with terms such as “prescription” or “Rx”
•2 cards—1 card for the medical benefit and 1 card for the pharmacy benefit. Health plans may
use a third-party provider for the pharmacy benefit, such as a pharmacy-benefit manager or PBM. In this
instance, the patient will have 1 card for the medical benefit that does not include pharmacy benefit
information. The patient will have a different insurance card for the pharmacy benefit information
Biogen patient start forms for specialty drugs may ask for medical and pharmacy benefit information. It is
important to complete Biogen patient start forms with information for both benefits when required. This will
provide the specialty distributor/pharmacy that is supplying the drug with the information needed to verify
the benefit.
Before a patient leaves the office, check the medical insurance card information to determine if you also
need to obtain the pharmacy benefit information from a different card.
It is important to review the patient’s insurance cards carefully to confirm that you
are using the proper card (medical or pharmacy) when completing Biogen patient
start forms or applying for claim reimbursement.
COMMERCIAL INSURANCE CARDS
If your patient has commercial insurance, they will most likely
be covered in one of the following ways:
Medical and pharmacy benefits with one carrier: 1 card
Health Star
Insurance
Comet Employer Group
Member Name
John Doe
Dependent Name
Jane Doe
Copays/Coinsurance
Primary Care $20
Specialist $40
Urgent Care $40
ER $100
Member ID
EXP000099900
Group No.
32155-000
Effective Date 11/01/11
Plan
STANDARD/OPTION
Patient copays for office and ER visits indicate
the medical benefit
The Rx symbol indicates that the pharmacy benefit
is included on this card
Rx
For illustrative purposes only.
Medical benefits with a health plan, pharmacy
benefits with a PBM: 2 cards
ProVantage
Health Insurance
Preferred Provider Network
MEMBER NAME
John Q Proof
MEMBER ID
ABC101202303
GROUP
Plan
PBMJ63
123456
Benefit Rx
Prevention Primary Care Specialist $0
$25
$45
Prescription Card
JOHN Q PROOF
ID 123456789
RXBIN:610029
RXPCN:CRK
RXGRP: CMCDX
Issuer:80840
Patient copays indicate the medical benefit
There is no prescription information on this card,
which means that the patient has a separate
pharmacy benefit card
Card is labeled for prescription, so it’s a
pharmacy benefit card
10000
Rx identification numbers indicate the
pharmacy benefit information
For illustrative purposes only.
Before your patient leaves the office, remember to obtain all of the benefit information from both
the medical and pharmacy cards so that Biogen patient start forms can be filled out completely and quickly.
If you do not see “prescription” or “Rx” indicated on a patient’s insurance card,
it’s a medical-benefit–only card.
USING THE APPROPRIATE INSURANCE CARD MAY
HELP PATIENTS START THERAPY MORE EFFICIENTLY
Tips to help your office
For commercial and Medicaid patients, some patients have 1 card and some patients have 2 cards
If the patient’s medical insurance card does not have “prescription,” “Rx,” or other similar terms
that indicate that the pharmacy benefit is included, you will need to gather the pharmacy benefit
information from a separate card
emember to check the Biogen patient start form before the patient leaves the office to confirm
R
that you have the required insurance information (medical and pharmacy) on file
onfirming that the prescription information on the Biogen patient start form is correct at the
C
beginning may eliminate unnecessary administrative work or callbacks
rior authorizations may be denied due to incomplete or insufficient information, not because
P
the patient does not have coverage for the drug
Reference: 1. Midwest Business Group on Health. Managing the rising costs of specialty pharmacy. January 29,
2014. http://ehcark.org/site/1747ehca/EHC_Arkansas_FINAL_012914.ppt. Accessed November 17, 2016.
© 2016 Biogen.
All rights reserved.
12/16
SMA-US-0181
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
SPINRAZA™ safely and effectively. See full prescribing information for
SPINRAZA.
SPINRAZA (nusinersen) injection, for intrathecal use
Initial U.S. Approval: 2016
__________________ INDICATIONS AND USAGE _________________
SPINRAZA is a survival motor neuron-2 (SMN2)-directed antisense
oligonucleotide indicated for the treatment of spinal muscular atrophy (SMA)
in pediatric and adult patients (1)
Laboratory Testing and Monitoring to Assess Safety (2.3)
•
At baseline and prior to each dose, obtain a platelet count, coagulation
laboratory testing, and quantitative spot urine protein testing
_____________ DOSAGE FORMS AND STRENGTHS ______________
Injection: 12 mg/5 mL (2.4 mg/mL) in a single-dose vial (3)
___________________ CONTRAINDICATIONS ___________________
None.
_______________ WARNINGS AND PRECAUTIONS _______________
•
_______________DOSAGE AND ADMINISTRATION ______________
SPINRAZA is administered intrathecally (2.1)
•
Dosing Information (2.1)
•
The recommended dosage is 12 mg (5 mL) per administration
•
Initiate SPINRAZA treatment with 4 loading doses; the first three
loading doses should be administered at 14-day intervals; the 4th loading
dose should be administered 30 days after the 3rd dose; a maintenance
dose should be administered once every 4 months thereafter
Important Preparation and Administration Instructions (2.2)
•
Allow to warm to room temperature prior to administration
•
Administer within 4 hours of removal from vial
•
Prior to administration, remove 5 mL of cerebrospinal fluid
•
Administer as intrathecal bolus injection over 1 to 3 minutes
Thrombocytopenia and Coagulation Abnormalities: Increased risk for
bleeding complications; testing required at baseline and before each dose
(5.1, 2.3)
Renal Toxicity: Quantitative spot urine protein testing required at
baseline and prior to each dose (5.2, 2.3)
___________________ ADVERSE REACTIONS ___________________
The most common adverse reactions that occurred in at least 20% of
SPINRAZA-treated patients and occurred at least 5% more frequently than in
control patients were lower respiratory infection, upper respiratory infection,
and constipation (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1800-456-2255 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 12/2016
FULL PRESCRIBING INFORMATION: CONTENTS*
1
2
3
4
5
6
8
INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
2.1 Dosing Information
2.2 Important Administration Instructions
2.3 Laboratory Testing and Monitoring to Assess Safety
DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
5.1
Thrombocytopenia and Coagulation Abnormalities
5.2
Renal Toxicity
ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Immunogenicity
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
11
12
13
14
16
17
8.5 Geriatric Use
DESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
CLINICAL STUDIES
14.1 Clinical Trial in Infantile-Onset SMA
HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not
listed.
1
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and
adult patients.
2
DOSAGE AND ADMINISTRATION
2.1
Dosing Information
SPINRAZA is administered intrathecally by, or under the direction of, healthcare professionals
experienced in performing lumbar punctures.
Recommended Dosage
The recommended dosage is 12 mg (5 mL) per administration.
Initiate SPINRAZA treatment with 4 loading doses. The first three loading doses should be
administered at 14-day intervals. The 4th loading dose should be administered 30 days after the
3rd dose. A maintenance dose should be administered once every 4 months thereafter.
Missed Dose
If a loading dose is delayed or missed, administer SPINRAZA as soon as possible, with at least
14-days between doses and continue dosing as prescribed. If a maintenance dose is delayed or
missed, administer SPINRAZA as soon as possible and continue dosing every 4 months.
2.2
Important Preparation and Administration Instructions
SPINRAZA is for intrathecal use only.
Prepare and use SPINRAZA according to the following steps using aseptic technique. Each vial
is intended for single dose only.
Preparation
•
•
•
•
•
Store SPINRAZA in the carton in a refrigerator until time of use.
Allow the SPINRAZA vial to warm to room temperature (25o C/77o F) prior to
administration. Do not use external heat sources.
Inspect the SPINRAZA vial for particulate matter and discoloration prior to
administration. Do not administer SPINRAZA if visible particulates are observed or if
the liquid in the vial is discolored.
Withdraw 12 mg (5 mL) of SPINRAZA from the single-dose vial into a syringe and
discard unused contents of the vial.
Administer SPINRAZA within 4 hours of removal from vial.
Administration
•
Consider sedation as indicated by the clinical condition of the patient.
•
•
•
2.3
Consider ultrasound or other imaging techniques to guide intrathecal administration of
SPINRAZA, particularly in younger patients.
Prior to administration, remove 5 mL of cerebrospinal fluid.
Administer SPINRAZA as an intrathecal bolus injection over 1 to 3 minutes using a
spinal anesthesia needle [see Dosage and Administration (2.1)]. Do not administer
SPINRAZA in areas of the skin where there are signs of infection or inflammation.
Laboratory Testing and Monitoring to Assess Safety
Conduct the following laboratory tests at baseline and prior to each dose of SPINRAZA and as
clinically needed [see Warnings and Precautions (5.1, 5.2)]:
• Platelet count
• Prothrombin time; activated partial thromboplastin time
• Quantitative spot urine protein testing
3
DOSAGE FORMS AND STRENGTHS
Injection: 12 mg/5 mL (2.4 mg/mL) nusinersen as a clear and colorless solution in a single-dose
vial.
4
CONTRAINDICATIONS
None.
5
WARNINGS AND PRECAUTIONS
5.1
Thrombocytopenia and Coagulation Abnormalities
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia,
have been observed after administration of some antisense oligonucleotides.
In a clinical study, 6 of 56 (11%) SPINRAZA-treated patients with normal or above normal
platelet levels at baseline developed a platelet level below the lower limit of normal, compared to
0 of 28 sham-procedure control patients. No patient had a platelet count less than 50,000 cells
per microliter in this study and no patient developed a sustained low platelet count despite
continued drug exposure.
Because of the risk of thrombocytopenia and coagulation abnormalities from SPINRAZA,
patients may be at increased risk of bleeding complications.
Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
5.2
Renal Toxicity
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after
administration of some antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney [see Clinical Pharmacology (12.3)]. In a
clinical study (mean treatment exposure 7 months), 17 of 51 (33%) SPINRAZA-treated patients
had elevated urine protein, compared to 5 of 25 (20%) sham-control patients. In a group of lateronset SMA patients (mean treatment exposure 34 months), 36 of 52 (69%) had elevated urine
protein. No elevations in serum creatinine or cystatin C were observed in these studies. Conduct
quantitative spot urine protein testing (preferably using a first morning urine specimen) at
baseline and prior to each dose of SPINRAZA. For urinary protein concentration greater than 0.2
g/L, consider repeat testing and further evaluation.
6
ADVERSE REACTIONS
The following serious adverse reactions are described in detail in other sections of the labeling:
6.1
•
Thrombocytopenia and Coagulation Abnormalities [see Warnings and Precautions (5.1)]
•
Renal Toxicity [see Warnings and Precautions (5.2)]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of SPINRAZA cannot be directly compared to rates in clinical
trials of other drugs and may not reflect the rates observed in practice.
The data described below reflect exposure to SPINRAZA in 173 patients (50% male, 82%
Caucasian), including 120 exposed for at least 6 months and 83 exposed for at least 1 year. The
safety of SPINRAZA was studied in infants with symptomatic SMA, approximately 1 month to
8 months of age at study entry; in a sham-controlled trial (n=80 for SPINRAZA, n=41 for
control); in open-label studies in presymptomatic and symptomatic infants (n=37), and in openlabel studies in later onset patients (n=56, 2 to 15 years of age at study entry). In the controlled
study in symptomatic infants, 41 patients were exposed for at least 6 months and 19 patients
were exposed for at least 12 months.
In the controlled study, baseline disease characteristics were largely similar in the SPINRAZAtreated patients and sham-control patients except that SPINRAZA-treated patients at baseline
had a higher percentage compared to sham-control patients of paradoxical breathing (89% vs
66%), pneumonia or respiratory symptoms (35% vs 22%), swallowing or feeding difficulties
(51% vs 29%) and requirement for respiratory support (26% vs 15%).
In the controlled study, the most common adverse reactions that occurred in at least 20% of
SPINRAZA-treated patients and occurred at least 5% more frequently than in control patients
were lower respiratory infection, upper respiratory infection, and constipation. Serious adverse
reactions of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control
patients (5%). Because patients in the controlled study were infants, adverse reactions that are
verbally reported could not be assessed in this study.
Table 1.
Adverse Reactions that Occurred in at Least 5% of SPINRAZA Patients and
Occurred at Least 5% More Frequently or At Least 2 Times as Frequently Than
in Control Patients in the Controlled Study in Infants with Symptomatic SMA
SPINRAZA 12 mg1
Sham-Procedure Control
N=80
N=41
%
%
Lower respiratory infection2
43
29
Upper respiratory infection3
39
34
Constipation
30
22
Teething
14
7
Upper respiratory tract
congestion
6
2
Aspiration
5
2
Ear infection
5
2
Scoliosis
5
2
Adverse Reactions
1
Four loading doses followed by 12 mg (5 mL) once every 4 months
Includes pneumonia, bronchiolitis, pneumonia viral, respiratory syncytial virus bronchiolitis, lower respiratory tract infection, pneumonia
bacterial, bronchitis, bronchitis viral, pneumonia moraxella, pneumonia parainfluenzae viral, lower respiratory tract infection viral, lung infection,
pneumonia influenza, pneumonia pseudomonal, pneumonia respiratory syncytial viral
3
Includes upper respiratory tract infection, nasopharyngitis, rhinitis, pharyngitis, or tracheitis
2
In an open-label clinical study in infants with symptomatic SMA, severe hyponatremia was
reported in a patient treated with SPINRAZA requiring salt supplementation for 14 months.
Cases of rash were reported in patients treated with SPINRAZA. One patient, 8 months after
starting SPINRAZA treatment, developed painless red macular lesions on the forearm, leg, and
foot over an 8-week period. The lesions ulcerated and scabbed over within 4 weeks, and resolved
over several months. A second patient developed red macular skin lesions on the cheek and hand
ten months after the start of SPINRAZA treatment, which resolved over 3 months. Both cases
continued to receive SPINRAZA and had spontaneous resolution of the rash.
SPINRAZA may cause a reduction in growth as measured by height when administered to
infants, as suggested by observations from the controlled study. It is unknown whether any effect
of SPINRAZA on growth would be reversible with cessation of treatment.
The most common adverse events in the open-label studies in later onset patients were headache
(50%), back pain (41%) and post lumbar puncture syndrome (41%). Most of these events
occurred within 5 days of lumbar puncture. Other adverse events in these patients were
consistent with adverse reactions observed in the controlled study.
6.2
Immunogenicity
The immunogenic response to nusinersen was determined in 126 patients with baseline and postbaseline plasma samples evaluated for anti-drug antibodies (ADAs). Five (4%) patients
developed treatment-emergent ADAs, of which 3 were transient and 2 were considered to be
persistent. There are insufficient data to evaluate an effect of ADAs on clinical response, adverse
events, or the pharmacokinetic profile of nusinersen.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the
assay. In addition, the observed incidence of antibody (including neutralizing antibody)
positivity in an assay may be influenced by several factors including assay methodology, sample
handling, timing of sample collection, concomitant medications and underlying disease. For
these reasons, comparison of the incidence of antibodies to SPINRAZA in the studies described
below with the incidence of antibodies in other studies or to other products may be misleading.
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
Risk Summary
There are no adequate data on the developmental risk associated with the use of SPINRAZA in
pregnant women. No adverse effects on embryofetal development were observed in animal
studies in which nusinersen was administered by subcutaneous injection to mice and rabbits
during pregnancy (see Data).
In the U.S. general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The
background risk of major birth defects and miscarriage for the indicated population is unknown.
Data
Animal Data
When nusinersen (0, 3, 10, or 25 mg/kg) was administered subcutaneously to male and female
mice every other day prior to and during mating and continuing in females throughout
organogenesis, no adverse effects on embryofetal development were observed. Subcutaneous
administration of nusinersen (0, 6, 12.6, or 25 mg/kg) to pregnant rabbits every other day
throughout organogenesis produced no evidence of embryofetal developmental toxicity.
8.2
Lactation
Risk Summary
There are no data on the presence of nusinersen in human milk, the effects on the breastfed
infant, or the effects of the drug on milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for SPINRAZA and
any potential adverse effects on the breastfed infant from SPINRAZA or from the underlying
maternal condition.
8.4
Pediatric Use
The safety and effectiveness of SPINRAZA in pediatric patients from newborn to 17 years have
been established [see Clinical Studies (14.1)].
Juvenile Animal Toxicity Data
In intrathecal toxicity studies in juvenile monkeys, administration of nusinersen (0, 0.3, 1, or 3
mg/dose for 14 weeks and 0, 0.3, 1, or 4 mg/dose for 53 weeks) resulted in brain histopathology
(neuronal vacuolation and necrosis/cellular debris in the hippocampus) at the mid and high doses
and acute, transient deficits in lower spinal reflexes at the high dose in each study. In addition,
possible neurobehavioral deficits were observed on a learning and memory test at the high dose
in the 53-week monkey study. The no-effect dose for neurohistopathology in monkeys (0.3
mg/dose) is approximately equivalent to the human dose when calculated on a yearly basis and
corrected for the species difference in CSF volume.
8.5
Geriatric Use
SMA is largely a disease of children and young adults; therefore, there is no geriatric experience
with SPINRAZA.
11
DESCRIPTION
SPINRAZA contains nusinersen, which is a modified antisense oligonucleotide, where the 2’hydroxy groups of the ribofuranosyl rings are replaced with 2’-O-2-methoxyethyl groups and the
phosphate linkages are replaced with phosphorothioate linkages. Nusinersen binds to a specific
sequence in the intron downstream of exon 7 of the SMN2 transcript. The structural formula is:
SPINRAZA is supplied as a sterile, preservative-free, colorless solution for intrathecal use in a
single-dose glass vial. Each 1 mL solution contains 2.4 mg of nusinersen (equivalent to 2.53 mg
of nusinersen sodium salt). Each 1 mL also contains calcium chloride dihydrate (0.21 mg) USP,
magnesium chloride hexahydrate (0.16 mg) USP, potassium chloride (0.22 mg) USP, sodium
chloride (8.77 mg) USP, sodium phosphate dibasic anhydrous (0.10 mg) USP, sodium phosphate
monobasic dihydrate (0.05 mg) USP, and Water for Injection USP. The product may contain
hydrochloric acid or sodium hydroxide to adjust pH. The pH is ~7.2.
The molecular formula of SPINRAZA is C234H323N61O128P17S17Na17 and the molecular weight is
7501.0 daltons.
12
CLINICAL PHARMACOLOGY
12.1
Mechanism of Action
SPINRAZA is an antisense oligonucleotide (ASO) designed to treat SMA caused by mutations
in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in
transgenic animal models of SMA, SPINRAZA was shown to increase exon 7 inclusion in SMN2
messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein.
12.2
Pharmacodynamics
Autopsy samples from patients (n=3) had higher levels of SMN2 messenger ribonucleic acid
(mRNA) containing exon 7 in the thoracic spinal cord compared to untreated SMA infants.
Cardiac Electrophysiology
In 121 patients with spinal muscular atrophy who received either SPINRAZA or sham-control,
QTcF values >500 ms and change from baseline values >60 ms were observed in 5% of patients
receiving SPINRAZA. Compared to the sham-control, there was no increase in the incidence of
cardiac adverse reactions associated with delayed ventricular repolarization in patients treated
with SPINRAZA.
12.3
Pharmacokinetics
Absorption
Intrathecal injection of SPINRAZA into the cerebrospinal fluid (CSF) allows nusinersen to be
distributed from the CSF to the target central nervous system (CNS) tissues. Following
intrathecal administration, trough plasma concentrations of nusinersen were relatively low,
compared to the trough CSF concentration. Median plasma Tmax values ranged from 1.7 to 6.0
hours. Mean plasma Cmax and AUC values increased approximately dose-proportionally up to a
dose of 12 mg.
Distribution
Autopsy data from patients (n=3) showed that SPINRAZA administered intrathecally was
distributed within the CNS and peripheral tissues, such as skeletal muscle, liver, and kidney.
Elimination
Metabolism
Nusinersen is metabolized via exonuclease (3’- and 5’)-mediated hydrolysis and is not a
substrate for, or inhibitor or inducer of CYP450 enzymes.
Excretion
The mean terminal elimination half-life is estimated to be 135 to 177 days in CSF, and 63 to 87
days in plasma. The primary route of elimination is likely by urinary excretion for nusinersen
and its chain-shortened metabolites. At 24 hours, only 0.5% of the administered dose was
recovered in the urine.
13
NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long-term studies in animals to evaluate the carcinogenic potential of nusinersen have not been
performed.
Mutagenesis
Nusinersen demonstrated no evidence of genotoxicity in in vitro (Ames and chromosomal
aberration in CHO cells) and in vivo (mouse micronucleus) assays.
Impairment of Fertility
When nusinersen (0, 3, 10, or 25 mg/kg) was administered by subcutaneous injection to mice
every other day prior to and during mating and continuing in females throughout organogenesis,
no adverse effects on male or female fertility were observed.
14
CLINICAL STUDIES
The efficacy of SPINRAZA was demonstrated in a double-blind, sham-procedure controlled
clinical trial in symptomatic infantile-onset SMA patients and was supported by open-label
clinical trials conducted in presymptomatic and symptomatic SMA patients.
14.1
Clinical Trial in Infantile-Onset SMA
This study was a multicenter, randomized, double-blind, sham-procedure controlled study in 121
symptomatic infants ≤ 7 months of age at the time of first dose, diagnosed with SMA (symptom
onset before 6 months of age). Patients were randomized 2:1 to receive either SPINRAZA or
sham injection.
A planned interim efficacy analysis was conducted based on patients who died, withdrew, or
completed at least 183 days of treatment. Of the 82 patients included in the interim analysis, 44%
were male and 56% were female. Age at first treatment ranged from 30 to 262 days (median
181). Eighty-seven (87%) of subjects were Caucasian, 2% were Black, and 4% were Asian.
Length of treatment ranged from 6 to 442 days (median 261 days). Baseline demographics were
balanced between the SPINRAZA and control groups with the exception of age at first treatment
(median age 175 vs. 206 days, respectively). The SPINRAZA and control groups were balanced
with respect to gestational age, birth weight, disease duration, and SMN2 copy number (2 copies
in 98% of subjects in boths groups). Median disease duration was 14 weeks. There was some
imbalance in age at symptom onset with 88% of subjects in the SPINRAZA group and 77% in
the control group experiencing symptoms within the first 12 weeks of life.
The primary endpoint assessed at the time of interim analysis was the proportion of responders:
patients with an improvement in motor milestones according to Section 2 of the Hammersmith
Infant Neurologic Exam (HINE). This endpoint evaluates seven different areas of motor
milestone development, with a maximum score between 2-4 points for each, depending on the
milestone, and a total maximum score of 26. A treatment responder was defined as any patient
with at least a 2-point increase (or maximal score of 4) in ability to kick (consistent with
improvement by at least 2 milestones), or at least a 1-point increase in the motor milestones of
head control, rolling, sitting, crawling, standing or walking (consistent with improvement by at
least 1 milestone). To be classified as a responder, patients needed to exhibit improvement in
more categories of motor milestones than worsening. Of the 82 patients who were eligible for
the interim analysis, a statistically significantly greater percentage of patients achieved a motor
milestone response in the SPINRAZA group compared to the sham-control group (see Table 2).
Figure 1 is a descriptive display of the distribution of net change from baseline in the total motor
milestone score for Section 2 of the HINE.
Although not statistically controlled for multiple comparisons at the interim analysis, the study
also assessed treatment effects on the Children’s Hospital of Philadelphia Infant Test of
Neuromuscular Disorders (CHOP-INTEND), which is an evaluation of motor skills in patients
with infantile-onset SMA. The CHOP-INTEND results are displayed in Table 2.
Table 2.
Motor Milestone Response and CHOP-INTEND Results
Endpoint
Motor Milestone (HINE Section 2)
Achievement of a motor milestone response
SPINRAZA-treated
patients (n=52)1
21 (40%)
p<0.0001
CHOP-INTEND Improvement from Baseline2
At least 4-points
33 (63%)
CHOP-INTEND Worsening from Baseline2
At least 4-points
2 (4%)
Sham-control
patients (n=30)1
0 (0%)
1 (3%)
12 (40%)
1
Analyses included all subjects who were alive with the opportunity for at least a 6-month (Day 183) assessment and
all subjects who died or withdrew from the study at the time of the interim analysis
2
Not statistically controlled for multiple comparisons at interim analysis
Figure 1. Net Change from Baseline in Total Motor Milestone Score (HINE) by Percent of
Subjects in the Interim Efficacy Set*
*For subjects who were alive and ongoing in the study, the change in total motor milestone score was calculated at
the later of Day 183, Day 302, or Day 394.
The results of the controlled trial in infantile-onset SMA patients were supported by open-label
uncontrolled trials conducted in symptomatic SMA patients who ranged in age from 30 days to
15 years at the time of first dose, and in presymptomatic patients, who ranged in age from 8 days
to 42 days at the time of first dose. The patients in these studies had or were likely to develop
Type 1, 2, or 3 SMA. Some patients achieved milestones such as ability to sit unassisted, stand,
or walk when they would otherwise be unexpected to do so, maintained milestones at ages when
they would be expected to be lost, and survived to ages unexpected considering the number of
SMN2 gene copies of patients enrolled in the studies.
The overall findings of the controlled trial in infantile-onset SMA and the open-label
uncontrolled trials support the effectiveness of SPINRAZA across the range of SMA patients,
and appear to support the early initiation of treatment with SPINRAZA.
16
HOW SUPPLIED/STORAGE AND HANDLING
16.1
How Supplied
SPINRAZA injection is a sterile, clear and colorless solution supplied as a 12 mg/5 mL (2.4
mg/mL) solution in a single-dose glass vial free of preservatives. The NDC is 64406-058-01.
16.2
Storage and Handling
Store in a refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton to protect from
light. Do not freeze.
SPINRAZA should be protected from light and kept in the original carton until time of use.
If no refrigeration is available, SPINRAZA may be stored in its original carton, protected from
light at or below 30oC (86oF) for up to 14 days.
Prior to administration, unopened vials of SPINRAZA can be removed from and returned to the
refrigerator, if necessary. If removed from the original carton, the total combined time out of
refrigeration should not exceed 30 hours at a temperature that does not exceed 25oC (77oF).
17
PATIENT COUNSELING INFORMATION
Thrombocytopenia and Coagulation Abnormalities
Inform patients and caregivers that SPINRAZA could increase the risk of bleeding. Inform
patients and caregivers of the importance of obtaining blood laboratory testing at baseline and
prior to each dose to monitor for signs of increased potential for bleeding. Instruct patients and
caregivers to seek medical attention if unexpected bleeding occurs [see Warnings and
Precautions (5.1)].
Renal Toxicity
Inform patients and caregivers that SPINRAZA could cause renal toxicity. Inform patients and
caregivers of the importance of obtaining urine testing at baseline and prior to each dose to
monitor for signs of potential renal toxicity [see Warnings and Precautions (5.2)].
Manufactured for:
Biogen Inc.
Cambridge, MA 02142
SPINRAZA is a trademark of Biogen.
© 2016 Biogen