Download Macugen®, pegaptanib - Medication Policy Manual | Index

Medication Policy Manual
Policy No: dru241
Topic: Macugen®, pegaptanib
Date of Origin: May 13, 2011
Committee Approval Date : May 8, 2015
Next Review Date: May 2016
Effective Date: September 1, 2015
IMPORTANT REMINDER
This Medical Policy has been developed through consideration of medical necessity, generally
accepted standards of medical practice, and review of medical literature and government
approval status.
Benefit determinations should be based in all cases on the applicable contract language. To the
extent there are any conflicts between these guidelines and the contract language, the contract
language will control.
The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to
dictate to providers how to practice medicine. Providers are expected to exercise their medical
judgment in providing the most appropriate care.
Description
Pegaptanib (Macugen) is an inhibitor of vascular endothelial growth factor (VEGF) that is
injected directly into the eye to prevent the formation of new blood vessels and reduce blood
vessel leakage and inflammation.
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Policy/Criteria
I.
Most contracts require prior authorization approval of pegaptanib (Macugen) prior to
coverage. Pegaptanib (Macugen) may be considered medically necessary when criteria A
and B below are met:
A.
At least one of the following diagnostic criteria 1 or 2 below are met:
1. A diagnosis of neovascular (wet) age-related macular degeneration. (See
Appendix 1)
OR
2. A diagnosis of diabetic macular edema. (See Appendix 1)
AND
B.
II.
III.
Treatment with bevacizumab (Avastin®) has been ineffective, not tolerated, or is
contraindicated.
Administration, Quantity Limitations, and Authorization Period
A.
OmedaRx does not consider pegaptanib (Macugen) to be a self-administered
medication.
B.
Authorization shall be reviewed at least annually to confirm that current
medical necessity criteria are met and that the medication is effective as
supported by clinical documentation indicating stabilization or improvement in
vision
Pegaptanib (Macugen) is considered investigational when used for all other conditions,
including but not limited to:
-
Cystoid macular degeneration
-
Glaucoma associated vascular disorders
-
Pathologic myopia
-
Radiation maculopathy
-
Retinal neovascularization
-
Retinal vein occlusion
-
In combination with other VEGF inhibitors, including but not limited to
aflibercept (Eylea), bevacizumab (Avastin), and ranibizumab (Lucentis)
Position Statement
-
-
Bevacizumab (Avastin®) is the best value VEGF inhibitor for the treatment of ocular
conditions. Bevacizumab (Avastin) does not require prior authorization for ocular
conditions.
Clinical trials of intravitreal VEGF inhibitors, including pegaptanib (Macugen), for the
treatment of neovascular (wet) age-related macular degeneration (wAMD) and diabetic
macular edema (DME) have shown evidence of efficacy for maintaining or improving
visual acuity.
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There is moderate certainty that pegaptanib (Macugen) is less effective in improving
visual acuity relative to bevacizumab (Avastin) and ranibizumab (Lucentis) in the
treatment of wAMD, and insufficient evidence to determine that one product is clinically
superior to another in the treatment of DME.
-
Clinical guidelines support the use of VEGF inhibitors, including bevacizumab (Avastin),
for the treatment of wAMD and DME.
-
Pegaptanib (Macugen) has been studied in other vascular-related ocular conditions. The
clinical benefit of pegaptanib (Macugen) in these indications is uncertain to date.
-
Clinical Efficacy
Neovascular (wet) Age-related Macular Degeneration (AMD)
-
There is moderate certainty that VEGF inhibitors, including pegaptanib (Macugen),
are effective for maintaining or improving vision in patients with wAMD based on
high quality systematic reviews.
*
*
*
-
-
-
One high quality systematic review of bevacizumab (Avastin) in the treatment of
wAMD concluded that it improves visual acuity and central retinal thickness
(moderate correlate to visual acuity) and is more effective than photodynamic
therapy (without verteporfin). [1]
One high quality systematic review of VEGF inhibitors concluded that
pegaptanib (Macugen) and ranibizumab (Lucentis) reduce the risk of visual
acuity loss in patients with wAMD versus sham or laser therapy. It also
concluded that ranibizumab (Lucentis®) may improve visual acuity; however, the
review did not include trials which evaluated bevacizumab (Avastin) or
aflibercept (Eylea®). [2]
One high quality systematic review of VEGF inhibitors concluded that
bevacizumab (Avastin), pegaptanib (Macugen), and ranibizumab (Lucentis) are
more effective than sham or laser treatment in maintaining or improving visual
acuity in patients with wAMD after one year of treatment. [3]
There is moderate certainty that pegaptanib (Macugen) is less effective than
bevacizumab (Avastin) and ranibizumab (Lucentis) in improving visual acuity in
patients with wAMD based on a high quality systematic review which demonstrated
that pegaptanib (Macugen) was associated with smaller improvements in visual acuity
compared to the other two VEGF inhibitors. This same study also concluded that there
were no major differences with respect to vision related outcomes in trials comparing
bevacizumab (Avastin) and ranibizumab (Lucentis). [3]
The American Academy of Ophthalmology (AAO) guidelines recommend aflibercept
(Eylea), bevacizumab (Avastin), or ranibizumab (Lucentis) for the treatment of wAMD.
The AAO does not recommend the use of pegaptanib (Macugen) in the treatment of
wAMD due to evidence showing that it does not improve visual acuity on average in
patients with new onset wAMD unlike other currently available VEGF inhibitors. [4]
Guidelines from the National Institute for Health and Clinical Excellence (NICE)
recommend ranibizumab (Lucentis) for the treatment of wet AMD. NICE does not
recommend treatment with pegaptanib (Macugen) for wet AMD due to an increase in
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overall costs for their population. [5] These guidelines have not been updated since the
approval of aflibercept (Eylea).
Diabetic Macular Edema (DME)
-
There is moderate certainty that VEGF inhibitors, including pegaptanib (Macugen),
improve visual acuity in patients with DME; however, there is insufficient evidence
demonstrating that one VEGF inhibitor is clinically superior to another in the treatment
of DME based on one high-quality systematic review and two randomized controlled
trials.
*
*
-
Pegaptanib (Macugen) has demonstrated improvements in visual acuity and vision
related quality of life versus sham injection when used for the treatment of DME. [6,7]
Pegaptanib (Macugen) has not been directly compared with any other VEGF
inhibitor in the treatment of DME.
A Cochrane systematic review concluded that aflibercept (Eylea), bevacizumab
(Avastin), and ranibizumab (Lucentis) are more effective than laser photocoagulation
in improving visual acuity (i.e. likelihood of gaining three or more lines of vision).
Although there were no significant sub-group differences in visual acuity between
the VEGF inhibitors, there was insufficient power to detect a difference between
them. [8]
AAO guidelines do not list pegaptanib (Macugen) as a treatment option for DME.
Aflibercept (Eylea), bevacizumab (Avastin), and ranibizumab (Lucentis) are the
recommended VEGF inhibitors for this condition, of which bevacizumab (Avastin) is the
lowest cost option. [9]
Retinal Vein Occlusion
Small, preliminary studies have reported inconsistent results of pegaptanib (Macugen) in the
treatment of macular edema due to both branch and central retinal vein occlusion. Larger, wellcontrolled clinical trials are needed to determine the clinical benefit of pegaptanib (Macugen) in
this condition. [10,11]
Other Uses
-
-
-
Published data evaluating pegaptanib (Macugen) in other conditions such as retinopathy
of prematurity, or in combination with bevacizumab (Avastin) for wet AMD are
preliminary. Larger well-controlled trials are needed to determine the clinical benefit of
pegaptanib (Macugen) in these settings. [12-14]
The use of pegaptanib (Macugen) in conjunction with other VEGF inhibitors, including
aflibercept (Eylea), bevacizumab (Avastin), and ranibizumab (Lucentis) is considered
investigational as there is no evidence evaluating the efficacy or safety of pegaptanib
(Macugen) when used in this manner.
Trials of pegaptanib (Macugen) in a variety of other conditions are ongoing and are
considered investigational due to lack of published data. [15]
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Safety
-
There is low certainty in the evidence demonstrating differences in adverse events
between intravitreous VEGF inhibitors.
*
*
-
-
A meta-analysis evaluating the cardiovascular (CV) safety of intravitreal VEGF
inhibitors in patients with wet AMD, DME, or retinal vein occlusion concluded
that VEGF inhibitors, specifically bevacizumab (Avastin) and ranibizumab
(Lucentis), are not associated with a significant increase in risk of systemic CV
and hemorrhagic events or in overall mortality, stroke, or CV mortality in elderly
patients. However, the studies and meta-analysis were not sufficiently powered
to correctly assess these risks. [16]
The trial conducted by the CATT research group comparing ranibizumab
(Lucentis) to bevacizumab (Avastin) for the treatment of wet AMD found the
following regarding safety: [17,18]

A statistically significant difference was seen at 52 weeks in the rates of
serious systemic adverse events between the ranibizumab (Lucentis) and
bevacizumab (Avastin) groups (19.0% vs 24.1%, P = 0.04).

A significant difference was also seen at 2 years [39.9% bevacizumab
(Avastin) vs 31.7% ranibizumab (Lucentis); adjusted risk ratio 1.30; 95% CI:
1.07, 1.57; P = 0.009].

This difference was largely due to hospitalizations for infections such as
pneumonia and urinary tract infections. It is uncertain if these events were
related to either medication.
Intravitreal VEGF inhibitors have also been associated with inflammation, blurred
vision, corneal edema, eye discharge and irritation, and hypertension. [19-21]
Additional serious adverse effects reported with intravitreous VEGF inhibitors include
endophthalmitis, retinal detachment and iatrogenic traumatic cataract. After injection,
patients should be advised to seek immediate care if the treated eye becomes red,
painful, sensitive to light, or they notice a change in vision. [19-21]
Bevacizumab (Avastin) is listed in national treatment guidelines and is recognized by
the Centers for Medicare and Medicaid Services as a safe and effective treatment option
for wet AMD and DME. [22,23]
*
Bevacizumab (Avastin), when used in the eye, must be extemporaneously
compounded to achieve the appropriate dose. In 2011, a group of cases of
endophthalmitis were reported with the use of bevacizumab (Avastin) which was
determined to be the result of unsafe practices by one compounding pharmacy.
[24-26]
*
*
While the use of bevacizumab (Avastin) continues to be associated with the risk
of endophthalmitis, all intravitreal injections, including commercially available
preparations of aflibercept (Eylea), pegaptanib (Macugen), and ranibizumab
(Lucentis) carry this risk. [19-21,27,28]
In 2013, the FDA passed the Drug Quality and Security Act which provides
better oversight of compounding pharmacies. A list of FDA approved
compounding facilities is available online. [29] In addition, the American Society
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of Retina Specialists has published online safety information about compounding
pharmacies to help retina specialists choose high-quality providers of
bevacizumab (Avastin). [24,30]
Dosing
-
Aflibercept (Eylea) 2 mg is injected intravitreously (into the eye) every 4 weeks for 12
weeks, then every 8 weeks. [21]
Bevacizumab (Avastin) 1.25 mg is injected intravitreously (into the eye) monthly or as
needed. [17,18]
Pegaptanib (Macugen) 0.3 mg is injected intravitreously (into the eye) every 6 weeks. [20]
Ranibizumab (Lucentis) 0.5 mg is injected intravitreously (into the eye) every 1 to 3
months. [19]
Appendix 1: List of covered diagnoses [31-33]
Covered Diagnosis
neovascular (wet) age-related
macular degeneration
Diabetic Macular Edema
Synonyms
Exudative senile macular degeneration
Age-related macular degeneration
Diabetic macular edema with diabetic retinopathy
Center involving diabetic macular edema
Diabetic retinal edema
Macular edema associated with
Retinal Vein Occlusion
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Clinically significant diabetic macular edema
(CSME)
Macular edema associated with Central vein
occlusion
Macular edema associated with Branch vein
occlusion
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Cross References
Avastin®, bevacizumab, OmedaRx Medication Policy Manual, Policy No. dru215
Eylea™, aflibercept, OmedaRx Medication Policy Manual, Policy No. dru267
Lucentis®, ranibizumab, OmedaRx Medication Policy Manual, Policy No. dru242
Codes
Number
Description
HCPCS
J2503
Injection, pegaptanib sodium, 0.3 mg
ICD-9
362.01362.06
Diabetic retinopathy
ICD-9
362.07
Diabetic macular edema
ICD-9
362.16
Retinal neovascularization not otherwise specified
ICD-9
362.3X
Retinal vascular occlusion
ICD-9
362.52
Exudative senile macular degeneration of retina
ICD-9
362.53
Cystoid macular degeneration
ICD-9
362.63
Glaucoma associated vascular disorders
ICD-9
362.83
Macular edema
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