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Spinraza™ - Nusinersen
Manufacturer: Biogen Inc.
FDA Approval Date: December 23, 2016
Jonathan Downs, PharmD Candidate
Spinraza™ - Nusinersen
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Spinraza™ -
(Nusinersen)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Spinraza™ (Nusinersen)
Spinraza™ - Nusinersen
Clinical Application
• Indications:
• Treatment of spinal muscular atrophy
(SMA) in pediatric and adult patients
• Place in therapy:
• First medication approved to treat
patients with SMA
Spinraza [package insert].
Spinraza™ - Nusinersen
Clinical Application
• Contraindications:
• None
• Warnings/Precautions:
• Thrombocytopenia and coagulation
abnormalities
• Nephrotoxicity
Spinraza [package insert].
Spinraza™ - Nusinersen
Clinical Application
• Pregnancy:
• Adverse events not observed in animal
studies
• Lactation:
• Unknown if excreted in breast milk
Spinraza [package insert].
Spinraza™ - Nusinersen
Drug Facts
• Pharmacology:
• Antisense oligonucleotide
• Increases exon 7 inclusion in SMN2
mRNA transcripts and production of
full-length SMN protein
Spinraza [package insert].
Spinraza™ - Nusinersen
Drug Facts
Spinraza [package insert].
Spinraza™ - Nusinersen
Drug Facts
• Pharmacokinetics:
A
Tmax: 1.6 - 6.0 h
D
Distributes to primarily to CNS; found in
skeletal muscles, liver, and kidneys
M
Metabolized via exonucluase (3’- and 5’)mediated hydrolysis
E
CSF t1/2 135-177 days, plasma t1/2 63-87 days
Spinraza [package insert].
Spinraza™ - Nusinersen
Drug Interactions
• Drug Interactions – Object Drugs:
• None
• Drug Interactions – Precipitant Drugs:
• None
Spinraza [package insert].
Spinraza™ - Nusinersen
Adverse Effects
• Common Adverse Effects:
(nusinersen%)[placebo%]
• Lower respiratory infection (43%) [29%
• Upper respiratory infection (39%) [34%]
• Constipation (30%) [22%]
• Serious Adverse Effects:
(nusinersen%)[placebo%]
• Atelectasis (14%) [5%]
Spinraza [package insert].
Spinraza™ - Nusinersen
Monitoring Parameters
• Efficacy/Toxicity Monitoring:
• Platelet count
• Coagulation laboratory testing
• Quantitative spot urine testing
• Should be performed at baseline and
prior to each dose
Spinraza [package insert].
Spinraza™ - Nusinersen
Prescription Information
• Dosing:
• Initial: Four 12mg loading doses
• First three doses administered 14 days apart
• Fourth loading dose given 30 days after third
dose
• Maintenance: 12mg IT every four months
• Hepatic/Renal: no adjustment needed
• Cost: – $125,000/dose
• FiercePharma. Accessed 01/15/2017
Spinraza [package insert].
Spinraza™ - Nusinersen
Literature Review
• Efficacy of nusinersen in symptomatic
infantile-onset SMA
• Study Design (N=121)
• Multicenter, randomized, double-blind,
sham-procedure controlled study
• Patients randomized 2:1 to receive either
nusinersen or sham injection
• Patients were ≤ 7 months of age at the
time of first dose
• Interim efficacy analysis was conducted
Spinraza [package insert].
(N=82)
Spinraza™ - Nusinersen
Literature Review
• Patient Characteristics
Nusinersen (N=52)
Sham (N=30)
Female, %
56%
Caucasian, %
87%
Symptoms w/in first 12
weeks of life, %
88%
77%
Age at first dose, days
175
206
Median disease
duration, weeks
14
Median length of
treatment, days
261
Spinraza [package insert].
Spinraza™ - Nusinersen
Literature Review
• Primary Efficacy Endpoint
• Improvement in motor milestones based
on the patient’s HINE score
• Assesses ability to kick, head control,
rolling, sitting, crawling, standing or
walking
• Secondary Efficacy Endpoint
• Improvement in a patient’s CHOP-
INTEND score
Spinraza [package insert].
Spinraza™ - Nusinersen
Literature Review
Endpoints
Nusinersen (N=52)
Sham (N=30)
Achievement of a motor
milestone response
21 (40%)
p < 0.0001
0 (0%)
CHOP-INTEND improvement
≥ 4 points from baseline
33 (63%)
1 (3%)
CHOP-INTEND worsening ≥ 4
points from baseline
2 (4%)
12 (40%)
Spinraza [package insert].
Spinraza™ - Nusinersen
Literature Review
• Conclusions
• Nusinersen is an effective new option for infants
diagnosed with SMA
• Patients treated with nusinersen were
significantly more likely to reach motor
milestones compared to the sham group
• Results support data from open-label studies
and appear to support the need for early
initiation of treatment with nusinersen
Spinraza [package insert].
Spinraza™ - Nusinersen
Summary
• Spinraza™ (nusinersen) is a novel treatment
option for patients with SMA
• Thrombocytopenia and nephrotoxicity are
potential complications associated with
nusinersen therapy
• Common side effects include respiratory
tract infections as well as constipation
• Nusinersen does not have any significant
drug-drug interactions and it does not
require any dose adjustments based on
hepatic or renal function
Spinraza™ - Nusinersen
References
1.
www.spinraza.com
2.
Spinraza [package insert]. Cambridge, MA:
Biogen Inc.; 2016.
3.
Staton T. Biogen’s $375K Spinranza price puts a
Sovaldi-style spotlight on rare disease meds.
FiercePharma. Published 3 Jan 2017.
http://www.fiercepharma.com/ pharma/biogen-s375k-spinraza-price-puts-a-sovaldi-stylespotlight-rare-disease-meds. Accessed 15 Jan
2017.