EYLEA HD® (aflibercept) Injection 8 mg Applications for Expanded U.S. Label and Prefilled Syringe Receive FDA Review Period Extension

Rhea-AI Summary

Regeneron Pharmaceuticals (NASDAQ: REGN) announced FDA review extensions for two EYLEA HD® (aflibercept) 8 mg regulatory submissions to Q4 2025. The extensions affect the prefilled syringe CMC Prior-Approval Supplement and a supplemental Biologics License Application for RVO treatment and expanded dosing options.

The delay stems from a recent FDA inspection of Catalent Indiana LLC, a third-party manufacturer acquired by Novo Nordisk. Novo Nordisk submitted a comprehensive response in August 2025 to address FDA observations. EYLEA HD remains available in vial form, with approved dosing intervals of 8-16 weeks for wAMD and DME patients, and 8-12 weeks for DR patients after initial monthly doses.

Positive

• None.

Negative

• FDA review period extended to Q4 2025 for two key EYLEA HD applications
• Manufacturing issues at third-party facility causing regulatory delays
• Delay affects both prefilled syringe availability and expanded indication approval

Insights

Pharmaceutical Regulatory Expert

FDA's extension of EYLEA HD regulatory reviews to Q4 2025 creates modest delays for Regeneron's product pipeline but doesn't affect current availability.

The FDA has extended the review period for two key EYLEA HD (aflibercept) Injection 8 mg regulatory submissions to Q4 2025. This affects both the prefilled syringe delivery format and the expanded indications that would include macular edema following retinal vein occlusion (RVO) plus more flexible monthly dosing options across approved uses.

What's happening behind the scenes is quite typical in pharmaceutical manufacturing: the delay stems from observations at a third-party manufacturer, Catalent Indiana LLC (now owned by Novo Nordisk), during a routine FDA inspection. The agency has classified Regeneron's subsequent information as a "major amendment" to the original applications, triggering the review extension.

The manufacturing issues appear to be addressable - Novo Nordisk submitted a comprehensive response in early August 2025. Importantly, EYLEA HD remains available in its vial administration form with its current approved dosing schedules for wet age-related macular degeneration, diabetic macular edema, and diabetic retinopathy.

This delay primarily impacts convenience (prefilled syringes are easier to administer than vials) and flexibility (monthly dosing would provide more options for certain patients). The extension was anticipated by Regeneron management and disclosed during their Q2 earnings announcement, suggesting minimal surprise impact on financial projections. Once manufacturing issues are resolved, the FDA should be able to move quickly on the applications.

TARRYTOWN, N.Y., Aug. 20, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and Drug Administration (FDA) has extended the target action dates to the fourth quarter of 2025 for two EYLEA HD^® (aflibercept) Injection 8 mg regulatory submissions. This includes a Chemistry, Manufacturing and Controls (CMC) Prior-Approval Supplement (PAS) for the EYLEA HD prefilled syringe and a supplemental Biologics License Application (sBLA) seeking approval for both the treatment of macular edema following retinal vein occlusion (RVO) and the broadening of the dosing schedule to include every 4-week (monthly) dosing across approved indications.

The FDA extended the review periods after determining that information provided since the completion of a recent inspection of a third-party manufacturer constituted a major amendment to each submission. As discussed during Regeneron’s second quarter 2025 earnings announcement, this delay was anticipated and resulted from observations during an FDA general site inspection at the filler for these regulatory applications, Catalent Indiana LLC, which was acquired by Novo Nordisk A/S in December 2024. Novo Nordisk submitted a comprehensive response in early August 2025 to address the observations noted by the FDA. It is our understanding that the FDA will be able to act expeditiously on these applications once the manufacturing issues have been resolved.

EYLEA HD remains available in the U.S. through vial administration. It is approved with dosing intervals from every 8 to 16 weeks for patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), and every 8 to 12 weeks for patients with diabetic retinopathy (DR), following 3 initial monthly doses.

About EYLEA HD
Over a decade ago, Regeneron introduced EYLEA, a vascular endothelial growth factor inhibitor, and transformed the treatment paradigm for certain serious chorioretinal vascular diseases. With a well-established efficacy and consistent safety profile from 16 pivotal trials, EYLEA is approved to treat vision-threatening conditions that impact patients from their earliest days, such as retinopathy of prematurity (ROP), to their later years, including diabetic macular edema (DME), diabetic retinopathy (DR), macular edema following retinal vein occlusion (RVO) and wet age-related macular degeneration (wAMD).

Pushing the boundaries of science further to meet patient needs, EYLEA HD was developed to achieve comparable efficacy and safety to EYLEA, but with fewer injections. EYLEA HD is supported by a robust body of research and is currently approved in the U.S. to treat patients with wAMD, DME and DR.

EYLEA HD (known as Eylea™ 8 mg in the European Union and Japan) is being jointly developed by Regeneron and Bayer AG. Regeneron maintains exclusive rights to EYLEA and EYLEA HD in the U.S. Bayer has licensed the exclusive marketing rights outside of the U.S., where the companies share equally the profits from sales of EYLEA and EYLEA HD.

About Ophthalmology Development at Regeneron
At Regeneron, we relentlessly pursue groundbreaking innovations in eye care science to help maintain the eye health of the millions of Americans impacted by vision-threatening conditions. Our expertise in angiogenesis and decades of research serve as our foundation, fueling our ongoing ambition to further innovate new solutions for patients. Our robust and diverse research and development program in ophthalmology includes efforts to potentially address additional serious eye diseases, including geographic atrophy (ongoing Phase 3 SIENNA clinical trial), glaucoma and certain inherited retinal diseases.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

INDICATIONS
EYLEA HD^® (aflibercept) Injection 8 mg is a prescription medicine approved for the treatment of patients with Wet Age-Related Macular Degeneration (AMD), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR).

EYLEA^® (aflibercept) Injection 2 mg is a prescription medicine approved for the treatment of patients with Wet Age-Related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), and Retinopathy of Prematurity (ROP) (0.4 mg).

IMPORTANT SAFETY INFORMATION

• EYLEA HD and EYLEA are administered by injection into the eye. You should not use EYLEA HD or EYLEA if you have an infection in or around the eye, eye pain or redness, or known allergies to any of the ingredients in EYLEA HD or EYLEA, including aflibercept.
• Injections into the eye with EYLEA HD or EYLEA can result in an infection in the eye, retinal detachment (separation of retina from back of the eye) and, more rarely, serious inflammation of blood vessels in the retina that may include blockage. Call your doctor right away if you or your baby (if being treated with EYLEA for Retinopathy of Prematurity) experience eye pain or redness, light sensitivity, or a change in vision after an injection.
• In some patients, injections with EYLEA HD or EYLEA may cause a temporary increase in eye pressure within 1 hour of the injection. Sustained increases in eye pressure have been reported with repeated injections, and your doctor may monitor this after each injection.
• In infants with Retinopathy of Prematurity (ROP), treatment with EYLEA 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, leading to heart attack or stroke in patients receiving EYLEA HD or EYLEA.
• The most common side effects reported in patients receiving EYLEA HD were cataract, increased redness in the eye, increased pressure in the eye, eye discomfort, pain, or irritation, blurred vision, vitreous (gel-like substance) 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 receiving EYLEA were 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 pre-term infants with ROP receiving EYLEA were separation of the retina from the back of the eye, increased redness in the eye, and increased pressure in the eye. Side effects that occurred in adults are considered applicable to pre-term infants with ROP, though not all were seen in clinical studies.
• You may experience temporary visual changes after an EYLEA HD or EYLEA injection and associated eye exams; do not drive or use machinery until your vision recovers sufficiently.
• For additional safety information, please talk to your doctor and see the full Prescribing Information for EYLEA HD and EYLEA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please click here for full Prescribing Information for EYLEA HD and EYLEA.

About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.

Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite^®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center^® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.

For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X.

Forward-Looking Statements and Use of Digital Media
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Products”) and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Product Candidates”) and research and clinical programs now underway or planned, including without limitation EYLEA HD^® (aflibercept) Injection 8 mg; uncertainty of the utilization, market acceptance, and commercial success of Regeneron’s Products (such as EYLEA HD) and Regeneron’s Product Candidates and the impact of the extended review periods for the EYLEA HD regulatory submissions to the U.S. Food and Drug Administration (“FDA”) discussed in this press release on any of the foregoing; whether Regeneron will ultimately be able to obtain FDA approval for EYLEA HD in a prefilled syringe, for the treatment of macular edema following retinal vein occlusion (“RVO”), and/or for every 4-week (monthly) dosing across approved indications and, if so, the timing of any such approvals; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron’s Product Candidates and new indications for Regeneron’s Products, such as EYLEA HD for the treatment of RVO as well as Regeneron’s Product Candidates for the treatment of geographic atrophy, glaucoma, or other serious eye diseases referenced in this press release; the ability of Regeneron’s collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron’s Products and Regeneron’s Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates and risks associated with tariffs and other trade restrictions; safety issues resulting from the administration of Regeneron’s Products (such as EYLEA HD) and Regeneron’s Product Candidates in patients, including serious complications or side effects in connection with the use of Regeneron’s Products and Regeneron’s Product Candidates in clinical trials; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commercialize Regeneron’s Products and Regeneron’s Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron’s Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement or copay assistance for Regeneron’s Products from third-party payors and other third parties, including private payor healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payors and other third parties and new policies and procedures adopted by such payors and other third parties; changes in laws, regulations, and policies affecting the healthcare industry; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron’s Products and Regeneron’s Product Candidates (including biosimilar versions of Regeneron’s Products); unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron’s agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics on Regeneron's business; and risks associated with litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts), risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA^® (aflibercept) Injection 2 mg), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron’s business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2024 and its Form 10-Q for the quarterly period ended June 30, 2025. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website (https://investor.regeneron.com) and its LinkedIn page (https://www.linkedin.com/company/regeneron-pharmaceuticals).

Contacts: Media Relations Julie Block Tel: +1 914-826-7083 julie.block@regeneron.com

Investor Relations Mark Hudson Tel: +1 914-847-3482 mark.hudson@regeneron.com

FAQ

What caused the FDA review extension for EYLEA HD applications?

The FDA extended the review after finding issues during an inspection of Catalent Indiana LLC, a third-party manufacturer, determining that subsequent information constituted a major amendment to the submissions.

When is the new FDA target action date for EYLEA HD applications?

The FDA has extended the target action dates to the fourth quarter of 2025 for both the prefilled syringe and expanded indication applications.

What are the current approved dosing intervals for EYLEA HD?

EYLEA HD is approved for dosing intervals of 8-16 weeks for wAMD and DME patients, and 8-12 weeks for DR patients, following 3 initial monthly doses.

Is EYLEA HD still available during the FDA review extension?

Yes, EYLEA HD remains available in the U.S. through vial administration while the prefilled syringe application is under review.

What new indications is Regeneron seeking for EYLEA HD?

Regeneron is seeking approval for treatment of macular edema following retinal vein occlusion (RVO) and broadening the dosing schedule to include every 4-week (monthly) dosing across approved indications.