EYLEA HD® (aflibercept) Injection 8 mg sBLA Accepted for FDA Priority Review for Both the Treatment of Macular Edema Following Retinal Vein Occlusion (RVO) and for Monthly Dosing in Approved Indications

Rhea-AI Summary

Regeneron Pharmaceuticals (NASDAQ: REGN) announced FDA's acceptance of Priority Review for EYLEA HD® (aflibercept) Injection 8 mg's supplemental Biologics License Application (sBLA). The application covers two key areas: treating macular edema following retinal vein occlusion (RVO) and enabling monthly dosing across approved indications.

The FDA target action date is set for August 19, 2025. If approved, EYLEA HD would pioneer 8-week dosing for RVO treatment after initial monthly doses, reducing injection frequency by half compared to other anti-VEGF therapies.

The Phase 3 QUASAR trial demonstrated EYLEA HD's non-inferior visual acuity gains at 36 weeks compared to EYLEA 2 mg monthly dosing. Safety profiles remained consistent with previous trials, with increased ocular pressure (5% vs 1.7%) being the main treatment-emergent adverse event.

Positive

• FDA Priority Review status could accelerate market entry
• Potential for 50% reduction in injection frequency compared to current treatments
• Non-inferior efficacy demonstrated in Phase 3 QUASAR trial
• Expanded dosing flexibility with monthly option across approved indications

Negative

• Higher rate of increased ocular pressure compared to standard EYLEA (5% vs 1.7%)
• Reported cases of endophthalmitis and retinal vasculitis in trial patients

Insights

Pharmaceutical Industry Analyst

FDA's Priority Review of EYLEA HD for RVO could significantly strengthen Regeneron's market position through reduced dosing frequency and expanded indications.

The FDA's acceptance of Regeneron's supplemental Biologics License Application (sBLA) for EYLEA HD® with Priority Review status represents a significant potential advancement for the company's ophthalmology franchise. The August 19, 2025 target action date accelerates the regulatory timeline, creating a near-term catalyst for Regeneron.

The application seeks approval for two key expansions: treatment of macular edema following retinal vein occlusion (RVO) and monthly dosing flexibility across all approved indications. Most crucially, if approved, EYLEA HD would become the first and only RVO treatment offering 8-week dosing after initial monthly loading doses – cutting injection frequency in half compared to all competing anti-VEGF therapies.

This dosing advantage creates a compelling competitive differentiation in the crowded ophthalmology market. For patients requiring long-term treatment, reducing injection frequency from monthly to once every two months delivers substantial quality-of-life improvements while potentially enhancing treatment adherence.

The strong Phase 3 QUASAR trial results, demonstrating non-inferior efficacy with 8-week dosing compared to standard monthly EYLEA, provide robust supporting evidence for approval. The safety profile appears generally consistent with the established EYLEA profile, with only minor differences in adverse event rates that don't appear concerning enough to derail approval.

This regulatory progress helps Regeneron defend and potentially expand its valuable EYLEA franchise against growing competition. By offering both extended interval and monthly dosing options, physicians gain greater flexibility to personalize treatment regimens – a key advantage in maintaining market leadership in retinal diseases.

Ophthalmology Specialist

EYLEA HD's potential 8-week dosing for RVO represents a breakthrough in reducing treatment burden while maintaining visual outcomes for patients.

The potential approval of EYLEA HD for RVO with 8-week dosing capability addresses one of the most significant challenges in retinal disease management – treatment burden. Currently, all approved anti-VEGF therapies for RVO require monthly injections, which creates substantial hardship for patients, many of whom are elderly and require assistance traveling to appointments.

The Phase 3 QUASAR trial data demonstrating non-inferior visual acuity gains with 8-week EYLEA HD dosing compared to monthly standard EYLEA is clinically meaningful. This efficacy combined with reduced injection frequency could transform the standard of care for RVO patients, who typically require long-term treatment to manage their condition.

From a safety perspective, the adverse event profile appears consistent with what we've seen in other EYLEA HD studies. The slight increase in ocular pressure events (5% vs 1.7%) bears monitoring but isn't uncommon with anti-VEGF agents. The intraocular inflammation rate of 0.5% for EYLEA HD compared to 1.3% for standard EYLEA is actually favorable and suggests good tolerability.

The flexibility to dose as frequently as monthly across approved indications would also provide significant clinical value, allowing physicians to individualize treatment based on disease activity and response. Some patients with more aggressive disease manifestations require more frequent dosing, while others can maintain excellent outcomes with extended intervals.

If approved, this expanded labeling would substantially improve the risk-benefit profile of anti-VEGF therapy for RVO by maintaining the visual benefits while reducing the cumulative risks and burdens associated with frequent intravitreal injections – a win for both patients and the healthcare system.

If approved, EYLEA HD would be the first and only treatment for RVO indicated for up to every 8-week dosing after an initial monthly dosing period – halving the number of injections that are indicated for all other anti-VEGF therapies

Potential for as frequent as monthly dosing for all approved indications would provide greater dosing flexibility for physicians and patients

TARRYTOWN, N.Y., April 17, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for EYLEA HD^® (aflibercept) Injection 8 mg. The sBLA seeks approval for EYLEA HD for both the treatment of macular edema following retinal vein occlusion (RVO), and for broadening the dosing schedule to include every 4-week (monthly) dosing across approved indications. The FDA target action date is August 19, 2025, following the use of a Priority Review voucher.

The sBLA is supported by data from across the EYLEA HD clinical program, including the Phase 3 QUASAR trial investigating EYLEA HD in RVO. As previously presented, QUASAR met its primary endpoint at 36 weeks, with EYLEA HD patients dosed every 8 weeks (after either 3 or 5 monthly doses), achieving non-inferior visual acuity gains compared to those receiving EYLEA^® (aflibercept) Injection 2 mg dosed every 4 weeks. Currently, all anti-VEGF therapies approved to treat RVO, including EYLEA, are indicated for monthly dosing.

In QUASAR, the safety profile of EYLEA HD (n=591) was similar to EYLEA (n=301) and remained generally consistent with the known safety profile of EYLEA HD in its pivotal trials for approved indications and with the established safety profile of EYLEA. Increased ocular pressure (5%) was the only ocular treatment-emergent adverse event that occurred in ≥5% of all EYLEA HD patients, compared to 1.7% of EYLEA patients. There was one case each of endophthalmitis and retinal vasculitis in all EYLEA HD patients, compared to two cases of endophthalmitis and no cases of retinal vasculitis in EYLEA patients. No cases of occlusive retinal vasculitis were reported. The rate of intraocular inflammation was 0.5% for EYLEA HD and 1.3% for EYLEA.

The safety and efficacy of EYLEA HD for the treatment of RVO and monthly dosing in approved indications has not been evaluated by any regulatory authority.

About the QUASAR Trial
QUASAR is a global double-masked, active-controlled Phase 3 trial evaluating the efficacy and safety of EYLEA HD in patients with macular edema secondary to RVO, including those with central retinal vein occlusion, branch retinal vein occlusion, or hemiretinal vein occlusion.

In the trial, patients were randomized into three groups to receive either EYLEA HD every 8 weeks following 3 initial monthly doses; EYLEA HD every 8 weeks following 5 initial monthly doses; or EYLEA every 4 weeks. The primary endpoint was mean change in best corrected visual acuity (BCVA) from randomization through week 36, as measured by the Early Treatment Diabetic Retinopathy Study letter score.

QUASAR is being operationalized by Bayer under a collaboration agreement with Regeneron.

About Retinal Vein Occlusion
RVO is a common cause of vision loss in adults and the second most common retinal vascular disease. RVO occurs when there is a blockage in a vein in the retina, which leads to a buildup of blood, restricted blood flow, increased pressure and sometimes pain in the eye. RVO may cause sudden blurry vision or vision loss and can ultimately result in serious complications like swelling in the eye called macular edema.

A protein called vascular endothelial growth factor (VEGF) is instrumental in causing the vascular leakage that leads to macular edema. When a vein in the retina is blocked, the levels of VEGF increase, which spurs new blood vessel growth. Too much VEGF can lead to the formation of abnormal blood vessels and may cause vision to become blurry. Anti-VEGF injections are commonly used to treat macular edema due to RVO.

There are two main types of RVO: central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). In CRVO, the buildup occurs in the eye’s central retinal vein and in BRVO, the buildup occurs in one of the smaller branch veins. Globally, RVO affects over 28 million people.

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; 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 Dupixent the treatment of macular edema following retinal vein occlusion (“RVO”) as well as the treatment of approved indications on a monthly dosing schedule (in each case pursuant to the supplemental Biologics License Application discussed in this press release); uncertainty of the utilization, market acceptance, and commercial success of Regeneron’s Products and Regeneron’s Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron’s Products (such as EYLEA HD for the treatment of patients with RVO) and Regeneron’s Product Candidates; 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; 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; 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 of Regeneron’s Products from third-party payers, including private payer 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 payers and new policies and procedures adopted by such payers; 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); the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; 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. 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 are the key benefits of EYLEA HD's potential FDA approval for RVO treatment?

If approved, EYLEA HD would be the first treatment allowing up to 8-week dosing intervals for RVO after initial monthly doses, reducing injection frequency by 50% compared to current anti-VEGF therapies.

When is the FDA expected to make a decision on EYLEA HD's sBLA for RVO treatment?

The FDA target action date is August 19, 2025, following the use of a Priority Review voucher.

What were the main safety findings for EYLEA HD in the QUASAR trial?

The main adverse event was increased ocular pressure (5% for EYLEA HD vs 1.7% for EYLEA), with similar overall safety profiles between treatments.

How did EYLEA HD perform in the Phase 3 QUASAR trial for RVO treatment?

EYLEA HD met its primary endpoint at 36 weeks, showing non-inferior visual acuity gains with 8-week dosing compared to EYLEA 2 mg monthly dosing.