FDA issues CRL for aflibercept 8 mg extended dosing for all indications | Image Credit: © Araki Illustrations - © Araki Illustrations - stock.adobe.com.

The US FDA has issued a complete response letter (CRL) to Regeneron Pharmaceuticals for a supplemental new drug application to add extended dosing intervals—up to every 24 weeks—to the label for EYLEA HD (aflibercept) Injection 8 mg, across all approved indications, according to a press release from the Pharmaceutical company.¹

No new safety or efficacy concerns raised

Regeneron stated that the FDA’s response did not cite any concerns with the safety or efficacy of aflibercept at currently approved doses or intervals. However, the agency did not agree with the proposed addition of dosing intervals beyond 16 weeks, which is the longest interval presently indicated on the label.

The company stated it is evaluating the federal agency's decision and "will determine a path forward in due course."

Aflibercept is currently approved for dosing every 8 to 16 weeks in patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), and every 8 to 12 weeks for diabetic retinopathy (DR), following 3 initial monthly doses. The company had sought to extend the maximum interval to 24 weeks, which would reduce treatment burden in eligible patients.

Background on EYLEA and EYLEA HD

EYLEA HD was designed to offer comparable efficacy and safety to the original aflibercept formulation but with fewer injections. Supported by a decade of clinical experience and 16 pivotal trials, aflibercept and EYLEA HD are approved for several vision-threatening conditions, including DME, DR, wAMD, and retinopathy of prematurity (ROP). EYLEA HD (also known as Eylea 8 mg outside the US) is co-developed with Bayer, which holds marketing rights outside the US.

At the time of its approval on February 13, 2023, aflibercept became the first pharmacologic treatment for preterm infants with ROP. The approval was backed by positive data from 2 phase 3 trials, FIREFLEYE and BUTTERFLEYE, which examined aflibercept 0.4 mg vs laser photocoagulation in infants with ROP. Data from both trials showed that approximately 80% of patients in the aflibercept-treated group achieved an absence of active ROP and unfavorable structural outcomes at 52 weeks of age. Additionally, there were no new safety signals observed for aflibercept in either of the trials.²

Because retinal blood vessels are mostly completely developed when an infant reaches full term, preterm infants are at an increased risk of developing abnormal blood vessels that can lead to retinal detachment and irreversible vision loss. While mild cases can improve over time without treatment, other cases may need treatment to prevent ROP from worsening, including visual impairment and blindness.

Ongoing research in ophthalmology

Beyond aflibercept, Regeneron is continuing to expand its ophthalmology pipeline, with ongoing Phase 3 investigation of geographic atrophy (SIENNA trial), as well as efforts in glaucoma and inherited retinal diseases. The company emphasized its commitment to advancing treatment options for patients with serious retinal conditions.¹

Indications and availability

Aflibercept 8 mg is FDA-approved for the treatment of wAMD, DME, and DR. The original 2 mg EYLEA formulation also holds approvals for macular edema following retinal vein occlusion (RVO) and ROP (0.4 mg formulation), in addition to wAMD, DME, and DR.

References:

1. Regeneron Provides Update on EYLEA HD® (aflibercept) Injection 8 mg Supplemental Biologics License Application. Regeneron. Press release. April 18, 2025. Accessed April 18, 2025. https://newsroom.regeneron.com/news-releases/news-release-details/regeneron-provides-update-eylea-hdr-aflibercept-injection-8-mg

2. Ebert, M. Aflibercept becomes first pharmacologic treatment for preterm infants with retinopathy of prematurity. Contemporary Pediatrics. February 14, 2023. Accessed April 18, 2025. https://www.contemporarypediatrics.com/view/aflibercept-becomes-first-pharmacologic-treatment-for-preterm-infants-with-retinopathy-of-prematurity