Download Page 1 of 9 Clinical Policy: aflibercept (Eylea), ranibizumab

Clinical Policy: aflibercept (Eylea), ranibizumab (Lucentis),
pegaptanib (Macugen), verteporfin (Visudyne)
Reference Number: ERX.XXXX.##
Effective Date: 05.17.17
Last Review Date:
Line of Business: Commercial
Revision Log
See Important Reminder at the end of this policy for important regulatory and legal
information.
Description
The following are injectable agents for ocular conditions requiring prior authorization:
aflibercept (Eylea®), ranibizumab (Lucentis®), pegaptanib (Macugen®), verteporfin
(Visudyne®)
FDA approved indication
Indication
Eylea
Lucentis
Macugen
Neovascular (Wet) Age-Related Macular
Degeneration (AMD)
Macular Edema Following Retinal Vein
Occlusion (RVO)
Diabetic Macular Edema (DME)
Diabetic Retinopathy in patients with
DME
Predominantly classic subfoveal choroidal
neovascularization due to age-related
macular degeneration, pathologic myopia or
presumed ocular histoplasmosis
Myopic Choroidal Neovascularization (mCNV)
X = FDA indication
X
X
X
X
X
X
X
X
X
Visudyne
X
X
Policy/Criteria
Provider must submit documentation (including office chart notes and lab results)
supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Envolve Pharmacy Solutions™ that Eylea,
Lucentis, Macugen, and Visudyne are medically necessary when the following criteria
are met:
I. Initial Approval Criteria
A. Neovascular (Wet) Age-Related Macular Degeneration (must meet all):
1. Diagnosis of neovascular (wet) age-related macular degeneration (AMD);
2. Prescribed by or in consultation with an ophthalmologist;
3. Request is for Eylea, Lucentis, Macugen, or Visudyne;
Page 1 of 9
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
4. For Lucentis or Eylea only: failure or clinically significant adverse effects to
Avastin unless contraindicated or clinically significant adverse effects are
experienced;
5. For Macugen or Visudyne only: failure or clinically significant adverse effects
to two of the following drugs: Avastin, Lucentis, or Eylea;
6. Dose does not exceed:
a. Eylea: 2 mg (0.05 mL) via intravitreal injection once every 4 weeks for the
first 3 months, then 2 mg (0.05 mL) via intravitreal injection once every 8
weeks;
b. Lucentis: 0.5 mg (0.05 mL) via intravitreal injection once every month;
c. Macugen: 0.3 mg (0.09 mL) via intravitreal injection once every 6 weeks;
d. Visudyne: 6 mg/m2 body surface area via intravenous injection once every
3 months.
Approval duration: Length of Benefit
B. Macular Edema Following Retinal Vein Occlusion (must meet all):
1. Diagnosis of macular edema following retinal vein occlusion;
2. Prescribed by or in consultation with an ophthalmologist;
3. Request is for Eylea or Lucentis;
4. Dose does not exceed:
a. Eylea: 2 mg (0.05 mL) via intravitreal injection once every 4 weeks;
b. Lucentis: 0.5 mg (0.05 mL) via intravitreal injection once every month.
Approval duration: Length of Benefit
C. Diabetic Macular Edema (must meet all):
1. Diagnosis of diabetic macular edema;
2. Prescribed by or in consultation with an ophthalmologist;
3. Request is for Eylea, Lucentis, or Macugen;
4. For Eylea and Lucentis only: failure or clinically significant adverse effects to
Avastin unless contraindicated or clinically significant adverse effects are
experienced
5. For Macugen only: failure or clinically significant adverse effects to Avastin,
Lucentis, and Eylea unless contraindicated or clinically significant adverse
effects are experienced
6. For Eylea only: patient’s baseline visual acuity is 20/50 or worse;
7. Dose does not exceed:
a. Eylea: 2 mg (0.05 mL) via intravitreal injection once every 4 weeks for the
first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once
every 8 weeks;
b. Lucentis: 0.3 mg (0.05 mL) per intravitreal injection once a month;
c. Macugen: 0.3 mg (0.09 mL) via intravitreal injection once every 6 weeks;
Approval duration: Length of Benefit
D. Diabetic Retinopathy in Patients with Diabetic Macular Edema (must meet
all):
1. Diagnosis of diabetic retinopathy with diabetic macular edema;
Page 2 of 9
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
2. Prescribed by or in consultation with an ophthalmologist;
3. Request is for Eylea or Lucentis;
4. Dose does not exceed:
a. Eylea: 2 mg (0.05 mL) via intravitreal injection once every 4 weeks for the
first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once
every 8 weeks;
b. Lucentis: 0.3 mg (0.05 mL) per intravitreal injection once a month.
Approval duration: Length of Benefit
E. Predominantly Classic Subfoveal Choroidal Neovascularization due to
Presumed Ocular Histoplasmosis (must meet all):
1. Diagnosis of predominantly classic Subfoveal Choroidal Neovascularization
due to presumed ocular histoplasmosis;
2. Prescribed by or in consultation with an ophthalmologist;
3. Request is for Visudyne;
4. Dose does not exceed 6 mg/m2 body surface area via intravenous injection
once every 3 months.
Approval duration: Length of Benefit
F. Myopic Choroidal Neovascularization (must meet all):
1. Diagnosis of myopic choroidal neovascularization;
2. Prescribed by or in consultation with an ophthalmologist;
3. Request is for Lucentis or Visudyne;
4. Dose does not exceed:
a. Lucentis: 0.5 mg (0.05 mL) via intravitreal injection once a month for up to
three months
b. Visudyne: 6 mg/m2 body surface area via intravenous injection once every
3 months
Approval duration: Length of Benefit
G. Other diagnoses/indications
1. Refer to ERX.XXXX.## if diagnosis is NOT specifically listed under section III
(Diagnoses/Indications for which coverage is NOT authorized)
II. Continued Therapy
A. All Indications (must meet all):
1. Currently receiving medication via a health plan affiliated with Envolve
Pharmacy Solutions or member has previously met initial approval criteria;
2. Documentation of positive response to therapy per one of the following:
a. Detained neovascularization;
b. Improvement in visual acuity;
c. Maintenance of corrected visual acuity from prior treatment;
d. Optical coherence tomography;
3. If request is for a dose increase, new dose does not exceed:
a. Eylea:
Page 3 of 9
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
i. AMD: 2 mg (0.05 mL) via intravitreal injection once every 4 weeks for the
first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once
every 8 weeks;
ii. ME following RVO: 2 mg (0.05 mL) via intravitreal injection once every 4
weeks;
iii. DME and DR in Patients with DME: 2 mg (0.05 mL) via intravitreal
injection once every 4 weeks for the first 5 injections, followed by 2 mg
(0.05 mL) via intravitreal injection once every 8 weeks;
b. Lucentis:
i. AMD, RVO, and mCNV: 0.5 mg (0.05 mL) via intravitreal injection once
every month;
ii. DME and DR in Patients with DME: 0.3 mg (0.05 mL) via intravitreal
injection once every month;
c. Macugen: 0.3 mg (0.9 mL) via intravitreal injection every 6 weeks;
d. Visudyne: 6 mg/m2 body surface area via intravenous injection once every
3 months.
Approval duration: Length of Benefit
B. Other diagnoses/indications (must meet 1 or 2):
1. Currently receiving medication via a health plan affiliated with Envolve
Pharmacy Solutions and documentation supports positive response to
therapy.
Approval duration: Duration of request or 12 months (whichever is less);
or
2. Refer to ERX.XXXX.## if diagnosis is NOT specifically listed under section III
(Diagnoses/Indications for which coverage is NOT authorized)
III. Diagnoses/Indications for which coverage is NOT authorized:
A. Non-FDA approved indications, which are not addressed in this policy, unless
there is sufficient documentation of efficacy and safety according to the off label
use policy – ERX.XXXX.## or evidence of coverage documents
IV.
Appendices/General Information
Appendix A: Abbreviation/Acronym Key
AMD: Age-related macular degeneration
DME: Diabetic macular edema
DR: Diabetic retinopathy
mCNV: Myopic choroidal neovascularization
ME: Macular edema
RVO: Retinal vein occlusion
Appendix B: General Information
This section is reserved for information that would be useful in making a coverage
determination, such as definitions of therapeutic failure not listed in the usage
guideline section.
Page 4 of 9
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
•
•
•
•
•
In the Comparison of AMD Treatments Trials study, the difference in mean
visual acuity improvement for patients treated with Avastin compared to
Lucentis was -1.4 letters (95% [CI],- 3.7 to 0.8) at two years. The proportion of
patients with arteriothrombotic events was similar in the Lucentis-treated
patients (4.7%) compared to the Avastin-treated patients (5.0%; p=0.89). The
proportion of patients with one or more systemic serious adverse events was
higher with Avastin (39.9%) than Lucentis (31.7%; adjusted risk ratio, 1.30;
95% CI, 1.07-1.57; p=0.009). Serious systemic adverse events included allcause mortality, non-fatal stroke, non-fatal myocardial infarction, vascular
death, venous thrombotic events and hypertension.
In the ANti-VEGF Antibody for the Treatment of Predominantly Classic
CHORoidal Neovascularisation in AMD (ANCHOR) trial, the number of
patients that lost fewer than 15 letters at 12 months was achieved by 96.4%
of patients treated with Lucentis 0.5 mg compared to 64.3% of patients
treated with Visudyne (p<0.001). Rate of intraocular inflammation was higher
for patients treated with Lucentis 0.5 mg at 15% compared to Visudyne at
2.8%.
In the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AgeRelated Macular Degeneration (VIEW)-1 trial, the difference in the number of
patients who lost fewer than 15 letters at 52 weeks between Eylea every 8
weeks compared to Lucentis was 0.6% (95.1% CI -0.32, 4.4). In terms of the
number of patients who gained at least 15 letters, the mean difference
between Eylea every 8 weeks was 6.6% (95.1% CI -1.0, 14.1). There were no
adverse events that were found to be significant from the Lucentis arm.
In the VEGF Inhibition Study in Ocular Neovascularization (VISION) trial, the
proportion of patients who lost fewer than 15 letters at week 54 for patients
treated with Macugen 0.3 mg was 70%, compared to 55% for placebo
(p<0.001). There was a significant difference in adverse events between
patients treated with Macugen compared to placebo for vitreous floaters (33%
vs. 8%, p<0.001), vitreous opacities (18% vs. 10%, p<0.001), and anterior
chamber inflammation (14% vs. 6%, p=0.001).
In a trial comparing Eylea, Avastin and Lucentis, the Diabetic Retinopathy
Clinical Research Network found in patients with diabetic macular edema that
when the initial visual-acuity letter score was 78 to 69 (equivalent to
approximately 20/32 to 20/40) (51% of participants), the mean improvement
was 8.0 with Eylea, 7.5 with Avastin, and 8.3 with Lucentis (P>0.50 for each
pair wise comparison). When the initial letter score was less than 69
(approximately 20/50 or worse), the mean improvement was 18.9 with Eylea,
11.8 with Avastin, and 14.2 with Lucentis (P<0.001 for Eylea vs. Avastin,
P=0.003 for Eylea vs. Lucentis, and P=0.21 for Lucentis vs. Avastin).
Appendix C: Therapeutic Alternatives
Drug
Dosing Regimen
Page 5 of 9
Dose
Limit/Maximu
m Dose
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
Drug
Avastin
(bevacizumab)
V.
Dosing Regimen
Neovascular (wet) macular degeneration:
1.25 to 2.5 mg administered by intravitreal
injection every 4 weeks
Neovascular glaucoma:
1.25 mg administered by intravitreal injection
every 4 weeks
Macular edema secondary to retinal vein
occlusion:
1 mg to 2.5 mg administered by intravitreal
injection every 4 weeks
Proliferative diabetic retinopathy:
1.25 mg administered by intravitreal injection 5
to 20 days before vitrectomy
Diabetic macular edema:
1.25 mg administered by intravitreal injection
Dosage and Administration
Drug Name
Indication
Aflibercept
(Eylea)
Ranibizumab
(Lucentis)
Dose
Limit/Maximu
m Dose
Dosing Regimen
Neovascular (Wet) AgeRelated Macular
Degeneration (AMD)
2 mg (0.05 mL) administered by
intravitreal injection once a month for
3 months then 2mg every 2 months.
Macular Edema Following
Retinal Vein Occlusion
2 mg (0.05 mL) administered by
intravitreal injection once a month
Diabetic Macular Edema
(DME) and Diabetic
Retinopathy (DR) in
patients with Diabetic
Macular Edema
2mg (0.05mL) administered by
intravitreal injection once a month for
the first 5 injections followed by 2 mg
via intravitreal injection once every 2
months. (Some patients may need
once monthly dosing after the first 5
doses)
0.5 mg (0.05 mL) administered by
intravitreal injection once a month.
Neovascular (Wet) AgeRelated Macular
Degeneration (AMD)
Alternative dosing:
Once monthly injections for three
months followed by 4-5 doses
dispersed among the following 9
months
Or
Macular Edema Following
Retinal Vein Occlusion
Diabetic Macular Edema
(DME) and Diabetic
Treatment may be reduced to one
injection every 3 months after the first
four injections if monthly injections are
not feasible.
0.5 mg (0.05 mL) administered by
intravitreal injection once a month.
0.3 mg (0.05 mL) administered by
intravitreal injection once a month
Page 6 of 9
2.5 mg
1.25 mg
2.5 mg
1.25 mg
1.25 mg
Maximum
Dose
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
Retinopathy (DR) in
patients with Diabetic
Macular
Myopic Choroidal
Neovascularization
(mCNV)
Pegaptanib
(Macugen)
Verteporfin
(Visudyne)
VI.
Neovascular (Wet) AgeRelated Macular
Degeneration (AMD)
Diabetic Macular Edema
Predominantly classic
subfoveal choroidal
neovascularization due to
age-related macular
degeneration, pathologic
myopia or presumed
ocular histoplasmosis
Product Availability
Drug
Aflibercept (Eylea)
Ranibizumab (Lucentis)
Pegaptanib (Macugen)
Verteporfin (Visudyne)
VII.
0.5 mg (0.05 mL) administered by
intravitreal injection once a month for
up to 3 months. Patients may be
retreated if needed.
0.3 mg (0.09 mL) administered by
intravitreal injection every 6 weeks
0.3 mg (0.09 mL) administered by
intravitreal injection once every 6
weeks x 3 doses
2
6 mg/m Body Surface Area IV diluted
with 5% dextrose to a final volume of
30 mL infused over 10 minutes
Availability
Single-use vial: 2 mg/0.05 mL
Single-use glass vials: 0.3 mg/0.05 mL, 0.5 mg/0.05 mL
Prefilled syringe: 0.3 mg/0.09 mL
Vial for reconstitution: 15mg (2mg/mL after
reconstitution)
References
1. Lucentis [Prescribing Information] South San Francisco, CA: Genentech, Inc.;
February 2015.
2. Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular
Degeneration: One-Year Findings from the IVAN Randomized Trial. The IVAN
Study Investigators, Chakravarthy U, Harding SP, Rogers CA, Downes SM,
Lotery AJ, Wordsworth S, Reeves BC. Ophthalmology. 2012;7:1399-1411. Epub
2012 May 11.
3. Comparison of Age-related Macular Degeneration Treatments Trials (CATT)
Research Group, Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, et al.
Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related
Macular Degeneration: Two-Year Results. Ophthalmology; 2012;7:1388-98.
4. Weigert G, Michels S, Sacu S, et al. Intravitreal bevacizumab (Avastin) therapy
versus photodynamic therapy plus intravitreal triamcinolone for neovascular agerelated macular degeneration: 6-month results of a prospective, randomised,
controlled clinical study. Br J Ophthalmol. 2008 Mar;92(3):356-360.
5. Bashshur Zf , Haddad Za, Schakal A, et al. Intravitreal Bevacizumab for
Treatment of Neovascular Age-related Macular Degeneration: A One-year
Prospective Study. Am J Ophthalmol. 2008;145:249–256.
Page 7 of 9
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
6. Yazdani S, Hendi K, Pakravan M, et al. Intravitreal bevacizumab for
neovascular glaucoma: a randomized controlled trial. J Glaucoma. OctoberNovember 2009;18(8):632-637.
7. Brouzas D, Charakidas A, Moschos M, et al. Bevacizumab (Avastin®) for the
management of anterior chamber neovascularization and neovascular glaucoma.
Clinical Ophthalmology. 2009;3:685-688.
8. Moraczewski AL, Lee RK, Palmberg PF, et al. Outcomes of treatment of
neovascular glaucoma with intravitreal vevacizumab. Br J Ophthalmol,
2009;93:589-593.
9. Costagliola C, Cipollone U, Rinaldi M, et al. Inravitreal bevacizumab
(Avastin®) injection for neovascular glaucoma: a survey of 23 cases throughout
12-month follow-up. Br J Clin Pharmacol, 2008;66(5):667-673.
10. di Lauro R, De Ruggiero P, di Lauro R, di Lauro MT, Romano MR. Intravitreal
bevacizumab for surgical treatment of severe proliferative diabetic retinopathy.
Graefes Arch Clin Exp Ophthalmol. 2010;248:785-791.
11. Rizzo S, Genovesi-Ebert F, Di Bartolo E, Vento A, Miniaci S, Williams G.
Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before
vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy
(PDR). Graefes Arch Clin Exp Ophthalmol. 2008 Jun;246(6):837-842.
12. Arevalo JF, Sanchez JG, Wu L, et al. Primary intravitreal bevacizumab for
diffuse diabetic macular edema. Ophthalmology. August 2009;116(8):1488-1497.
13. Roh MI, Byeon SH, Kwon OW. Repeated intravitreal injection of
bevacizumab for clinically significant diabetic macular edema. Retina, the Journal
of Retinal and Vitreous Diseases. 2008; 28(9): 1314-1318.
14. Kook D, Wolf A, Kreutzer T, et al. Long-term effect of intravitreal
bevacizumab (Avastin) in patients with chronic diffuse diabetic macular edema.
Retina, the Journal of Retinal and Vitreous Diseases. 2008; 28(8): 1053-1060.
15. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for
neovascular age-related macular degeneration. N Engl J Med. 2006;334:1432–
1444.
16. Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR;
VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group.
Pegaptanib for neovascular age-related macular degeneration. N Engl J Med.
2004 Dec 30;351(27):2805-16.
17. Product Dossier: EyleaTM (aflibercept). Tarrytown; November 2011.
Regeneron Pharmaceuticals, Inc. Data reviewed February 14, 2012.
18. Visudyne [Prescribing information]. Bridgewater, NJ: Valeant
Pharmaceuticals: April 2016.
19. Macugen [Prescribing information]. San Dimas, CA: Gilead Sciences, Inc.:
October 2011.
20. Eylea [Prescribing Information]. Tarrytown, NY: Regeneron Pharmaceuticals,
Inc.: May 2016.
21. American Hospital Formulary Service Drug Information. Available at:
http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 14, 2016
Page 8 of 9
CLINICAL POLICY
aflibercept, ranibizumab, pegaptanib, verteporfin
22. JuneGlassman AR et al. Aflibercept, Bevacizumab, or Ranibizumab for
Diabetic Macular Edema. NEJM February, 2015 published online ahead of print
(DOI: 10.1056/NEJMoa1414264)
23. Micromedex® Healthcare Series [Internet database]. Greenwood Village,
Colo: Thomson Healthcare. Updated periodically. Accessed June 2016.
24. Clinical Pharmacology Web site. Available at: http://cpip.gsm.com/. Accessed
June 14, 2016.
Reviews, Revisions, and Approvals
Date
Policy created
Corrected Lucentis product availability to 0.5 mg/0.05
mL
02/17
04/17
P&T
Approval
Date
05/17
Important Reminder
This clinical policy has been developed by appropriately experienced and licensed
health care professionals based on a review and consideration of currently available
generally accepted standards of medical practice; peer-reviewed medical literature;
government agency/program approval status; evidence-based guidelines and positions
of leading national health professional organizations; views of physicians practicing in
relevant clinical areas affected by this clinical policy; and other available clinical
information.
This Clinical Policy is not intended to dictate to providers how to practice medicine, nor
does it constitute a contract or guarantee regarding payment or results. Providers are
expected to exercise professional medical judgment in providing the most appropriate
care, and are solely responsible for the medical advice and treatment of members.
This policy is the property of Envolve Pharmacy Solutions. Unauthorized copying, use,
and distribution of this Policy or any information contained herein is strictly prohibited.
By accessing this policy, you agree to be bound by the foregoing terms and conditions,
in addition to the Site Use Agreement for Health Plans associated with Envolve
Pharmacy Solutions.
©2017 Envolve Pharmacy Solutions. All rights reserved. All materials are exclusively
owned by Envolve Pharmacy Solutions and are protected by United States copyright
law and international copyright law. No part of this publication may be reproduced,
copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any
form or by any means, or otherwise published without the prior written permission of
Envolve Pharmacy Solutions. You may not alter or remove any trademark, copyright or
other notice contained herein.
Page 9 of 9