Regeneron announces US FDA complete response letter for aflibercept 8 mg (Eylea HD) supplemental Biologics License Application

In March, Regeneron filed an additional sBLA seeking to extend the dosing schedule to include every-4-week dosing across approved indications. Image credit: ©Araki Illustrations – stock.adobe.com

The United States Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Regeneron Pharmaceuticals for its supplemental Biologics License Application (sBLA). The sBLA was submitted for the addition of extended dosing intervals (up to every 24 weeks) for aflibercept Injection 8 mg (Eylea HD) across all approved indications.¹

According to the company, the CRL does not identify any safety or efficacy issues with aflibercept 8 mg. However, the FDA did not agree with the company’s proposal to add additional extended dosing intervals greater than every 16 weeks, which is the maximum dosing interval currently indicated in the label.

Aflibercept 8 mg is currently approved with dosing intervals from every 8 to 16 weeks for patients with wet age-related macular degeneration (wAMD) and diabetic macular oedema (DMO), and every 8 to 12 weeks for patients with diabetic retinopathy (DR), following three initial monthly doses. In March of 2024, Regeneron published the 1-year results of the pivotal PULSAR and PHOTON trials for aflibercept 8 mg for wAMD and DME in The Lancet. The 8mg dosage was found to be noninferior and demonstrated clinically equivalent visual gains at 48 weeks for both 12- and 16-week dosing regimens, following three initial monthly dosings. Previously, Regeneron had investigated three initial monthly doses in PULSAR and five monthly initial doses in PHOTON.²

In March, Regeneron filed an additional sBLA seeking approval for aflibercept 8 mg for both the treatment of macular oedema following retinal vein occlusion (RVO), and for broadening the dosing schedule to include every-4-week, or monthly, dosing across approved indications. An application for expanding the indication for RVO was filed with the European Medicines Agency in early April. The FDA target action date for a congruent application in the US is currently set for August 19, 2025. Regeneron noted it is evaluating the FDA’s decision, and will determine a path forward “in due course.”

In the United States, Regeneron maintains exclusive rights to aflibercept 2 mg (Eylea 2 mg) and aflibercept 8 mg (Eylea HD); outside the US, Bayer has licensed exclusive marketing rights

Indications and safety information

• Both Eylea HD and aflibercept 2 mg (Eylea) are injections administered to the eye.
• Eylea HD is an 8 mg injection approved for the treatment of wet AMD, DMO and DR
• Eylea is a 2 mg injection approved for the treatment of wet AMD, macular oedema following RVO, DMO, DR and retinopathy of prematurity (ROP)
• The most common side effects reported in patients being treated with aflibercept 8 mg include: cataract, increased redness in the eye, increased pressure in the eye, eye discomfort, pain or irritation, blurred vision, vitreous floaters, vitreous detachment, injury to the outer layer of the eye and bleeding in the back of the eye
• The most common side effects reported in patients being treated with aflibercept 2 mg include: increased redness in the eye, eye pain, cataract, vitreous detachment, vitreous floaters, moving spots in the field of vision and increased pressure in the eye
• The most common side effects reported in preterm infants with ROP receiving aflibercept 2 mg include: separation of the retina from the back of the eye, increased redness in the eye and increased pressure in the eye
• Injections with aflibercept 2 mg and aflibercept 8 mg can result in an infection of the eye, retinal detachment, and in rare cases, serious inflammation of blood vessels that may include blockage
• A temporary increase in eye pressure within 1 hour of the injection can happen in some patients
• Infants with ROP being treated with aflibercept 8 mg will need extended periods of ROP monitoring
• There is a potential but rare risk of serious and sometimes fatal side effects related to blood clots that could lead to a heart attack or stroke when using aflibercept 2 mg or aflibercept 8 mg

Reference:

1. Regeneron provides update on EYLEA HD (aflibercept) injection 8 mg supplemental biologics license application. Regeneron. Published April 18, 2025. Accessed April 21, 2025. https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-update-eylea-hdr-aflibercept-injection-8-mg

2. Harp MD. Regeneron announces publication of one-year results from PULSAR and PHOTON trials. Ophthalmology Times. March 8, 2024. Accessed April 21, 2025. https://www.ophthalmologytimes.com/view/regeneron-announces-publication-of-one-year-results-from-pulsar-and-photon-trials