FDA Approves Higher-Dose Version of Aflibercept

The FDA approved Eylea HD (aflibercept), a high-dose version of Eylea, for the treatment of several ophthalmic conditions including advanced neovascular age-related macular degeneration (wet AMD), diabetic macular edema, and diabetic retinopathy.

“The FDA approval of Eylea HD is an important advancement in retinal care…. With Eylea HD, patients with wet [AMD] or diabetic retinal disease can now receive less frequent injections after their initial monthly doses and still experience the similar visual gains, anatomic improvements and safety profile of Eylea,” Peter Kaiser, MD, Chaney Family Endowed Chair in ophthalmology research at the Cole Eye Institute and professor of ophthalmology at Cleveland Clinic Lerner College of Medicine, said in a statement issued by Regeneron.

The new version features an 8-mg intravitreal injection compared with the 2-mg dose for the original product. Aflibercept is an anti–vascular endothelial growth factor agent designed to block the growth of new blood vessels and inhibit fluid from passing through blood vessels in the eye. The original Eylea product was approved in 2011.

The dosing schedule for Eylea HD is 8 mg every 4 weeks for 3 months, then 8 mg every 8 to 16 weeks for wet AMD or diabetic macular edema and every 8 to 12 weeks for diabetic retinopathy.

The regulatory decision was based on data from the 48-week PULSAR and PHOTON double-masked, active-controlled trials that compared the safety, efficacy, and clinical outcomes of Eylea HD vs Eylea. The PULSAR trial (n = 1009) evaluated the medicines in wet AMD and the PHOTON trial (n = 658) tested them in diabetic macular edema.

In both analyses, Eylea HD demonstrated clinically equivalent vision gains at 48 weeks with 12- and 16-week dosing regimens after only 3 initial monthly doses compared with an 8-week dosing regimen of Eylea after initial monthly doses (PULSAR, 3 doses; PHOTON, 5 doses). Most patients randomized at baseline to receive Eylea HD 12- or 16-week regiments were able to maintain the dosing intervals through 48 weeks.

Cataract, conjunctival hemorrhage, intraocular pressure increases, ocular discomfort/eye pain/eye irritation, vision blurring, vitreous floaters, vitreous detachment, corneal epithelium defect, and retinal hemorrhage were noted as the most common (at least 3%) adverse reactions related to Eylea HD administration.

“More than 10 years ago, we fundamentally changed the way that certain serious retinal diseases were treated with the introduction of Eylea. With the approval of Eylea HD, we have elevated the high standard that Eylea set,” George D. Yancopoulos, MD, PhD, board cochair, president, and chief scientific officer at Regeneron, said in the statement.

The approval comes after Regeneron and Bayer, the companies responsible for Eylea and Eylea HD, received a complete response letter (CRL) from the FDA for its biologics license application for Eylea HD in June 2023. In the CRL, the FDA cited issues regarding the manufacturing facility inspection at a third-party filler and did not cite any issues with the safety and efficacy data, the product itself, the trial design, or labeling or drug substance manufacturing.

As part of a 2016 commercialization agreement, Regeneron and Bayer collaborate on the global development and commercialization of Eylea, Eylea HD, and REGN2176-3, a platelet-derived growth factor receptor-β antibody rinucumab candidate that has been coformulated with aflibercept. Under the agreement, Regeneron is tasked with manufacturing and development and Bayer has global exclusive marketing rights outside the United States to the combination products and will share potential profits equally with Regeneron. Within the United States, Regeneron has exclusive commercialization rights to Eylea and Eylea HD.

Regulatory filings for Eylea HD are under review in the European Union and Japan. Regeneron said that it plans to file more submissions in other global markets in the future.

Reference

Eylea HD (aflibercept) injection 8 mg approved by FDA for treatment of wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and diabetic retinopathy (DR). News release. Regeneron. August 18, 2023. Accessed August 31, 2023. https://investor.regeneron.com/news-releases/news-release-details/eylea-hd-aflibercept-injection-8-mg-approved-fda-treatment-wet