Aflibercept 8 mg (Eylea HD) Approved by FDA for Wet AMD, DME, and Diabetic Retinopathy

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Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved aflibercept 8 mg (Eylea HD) for the treatment of wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy, making it the first and only treatment approved for wet AMD and DME for immediate dosing at 8- week and up to 16-week intervals following 3 initial monthly doses.¹

Announced on August 18, 2023, by Regeneron Pharmaceuticals, the approval, which is based on data from the PULSAR and PHOTON trials, comes less than 2 months after the FDA issues the company a Complete Response Letter (CRL) citing concerns related to inspection findings at a third-party filler in June 2023.^1,2

“The FDA approval of EYLEA HD is an important advancement in retinal care,” said 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.¹ “With EYLEA HD, patients with wet age-related macular degeneration 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.”

The year 2023 has been a proverbial rollercoaster for aflibercept 8 mg and Regeneron, beginning in February 2023 with the submission of a Biologics License Application (BLA) to the FDA.³ Following submission of the BLA, the company announced the receipt of a CRL from the FDA on June 27, 2023. In their announcement, Regeneron pointed out the FDA referred to an ongoing review of inspection findings from a third-party filler involved with the drug development and the FDA did not require additional trial data.²

The August 18, 2023, approval of aflibercept 8 mg is based on data from the aforementioned PULSAR and PHOTON trials, which included patient populations with wet AMD and DME, respectively. Designed as double-masked, active-controlled trials, both trials randomize patients in 3 treatment groups where they received aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or aflibercept 2 mg every 8 weeks. The 48-week results from the trials suggested aflibercept 8mg demonstrated noninferiority and clinically equivalent vision gains at 48 weeks with both 12- and 16-week dosing regimens after only 3 initial monthly doses when compared to an aflibercept 2 mg with 8-week dosing regimen after initial monthly doses.¹

On August 10, 2023, Regeneron announced positive 96-week topline data from the PULSAR trial. These results indicated 88% were on a dosing interval of 12 weeks or more at the end of 96 weeks and 78% maintained dosing intervals of 12 weeks or greater throughout the duration of the 96-week study period, compared to 83% throughout the first year of study. The announcement also pointed out 71% of those who completed the 96-week follow-up met the extension criteria for even longer dosing intervals, including 47% for intervals of 20 weeks or more and 28% for intervals of 24 weeks or more.⁴

“I look forward to offering EYLEA HD to my patients as a new treatment option that builds off of the established efficacy and safety profile of EYLEA,” said Allen C. Ho, MD, Director of Retina Research and Co-Director of the Retina Service of Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University.¹ “In its clinical trial program, EYLEA HD demonstrated an unprecedented ability to maintain vision with extended dosing intervals, which created an exciting new advancement in the treatment of our patients with serious retinal diseases.”

Earlier in the day on August 18, 2023, Regeneron announced the approval of pozelimab-bbfg (Veopoz) for the treatment of for the treatment of adult and pediatric patients 1 year of age and older with CHAPLE disease. In this release, the company noted the preapproval inspection issues related to the BLA for aflibercept 8 mg had been addressed and FDA action on the aflibercept 8 mg BLA was expected within the next few weeks.⁵

“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,” said George D. Yancopoulos, MD, PhD, board cochair, president, and chief scientific officer at Regeneron and a principal inventor of EYLEA.¹ “Our continued commitment to retinal diseases resulted in an important scientific innovation – evolving the proven efficacy and safety of EYLEA into a new treatment, EYLEA HD, that provides lasting vision control with even fewer injections to further benefit those living with wet age-related macular degeneration or diabetic retinal diseases."

References:

1. ^{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). Regeneron Pharmaceuticals Inc. August 18, 2023. Accessed August 19, 2023. https://investor.regeneron.com/news-releases/news-release-details/eylea-hd-aflibercept-injection-8-mg-approved-fda-treatment-wet.}
2. ^{Iapoce C, Kunzmann K. FDA issues complete response letter for Aflibercept 8 mg as AMD, DME treatment. HCP Live. June 27, 2023. Accessed August 19, 2023. https://www.hcplive.com/view/fda-issues-complete-response-letter-aflibercept-8-mg-amd-dme.}
3. ^{Iapoce C. FDA accepts bla for aflibercept 8mg for priority review. HCP Live. February 24, 2023. Accessed August 19, 2023. https://www.hcplive.com/view/fda-accepts-bla-aflibercept-8mg-priority-review.}
4. ^{Iapoce C. Pulsar trial shows durability of aflibercept 8 mg in wet AMD at 2 years. HCP Live. August 10, 2023. Accessed August 19, 2023. https://www.hcplive.com/view/pulsar-trial-durability-aflibercept-8-mg-wet-amd-2-years.}