Eylea HD (high-dose aflibercept) / Regeneron, Bayer - LARVOL DELTA

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 (GlobeNewswire) - "Regeneron Pharmaceuticals...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..."

FDA filing • PDUFA • Priority review • Macular Edema • Retinal Vein Occlusion

Regeneron Provides Update on EYLEA HD (aflibercept) Injection 8 mg Supplemental Biologics License Application (GlobeNewswire) - "Regeneron Pharmaceuticals, Inc...announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the supplemental Biologics License Application (sBLA) for the addition of extended dosing intervals (up to every 24 weeks) for EYLEA HD (aflibercept) Injection 8 mg across all approved indications...The CRL did not identify any issues with the safety or efficacy of EYLEA HD in its approved indications and dosing regimens. The FDA did not agree with Regeneron’s proposal to add additional extended dosing intervals (greater than every 16 weeks, which is the maximum dosing interval currently indicated in the label). Regeneron is evaluating the FDA’s decision and will determine a path forward in due course....EYLEA HD 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..."

CRL • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy

Clinical Outcomes in nAMD with Aflibercept 8 mg in the Phase 2 CANDELA Study. (PubMed, Ophthalmol Retina) - "In this post hoc analysis of the CANDELA trial, eyes with neovascular age-related macular degeneration treated with aflibercept 8 mg achieved improved anatomic and visual outcomes, suggesting therapeutic benefit compared with aflibercept 2 mg."

Clinical data • Journal • P2 data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Bayer files for approval of aflibercept 8 mg for treatment of retinal vein occlusion in EU (Bayer Press Release) - "Bayer has submitted an application to the European Medicines Agency (EMA) seeking approval of aflibercept 8 mg (114.3 mg/ml solution for injection) for the treatment of patients with macular edema following retinal vein occlusion (RVO) including central, branch and hemiretinal vein occlusion. This would be the third indication for aflibercept 8 mg supporting the blockbuster status of Eylea. The submission is based on positive results from the global randomized, double-masked, active-controlled phase III QUASAR study....The QUASAR clinical study demonstrated that approximately 90% of patients on aflibercept 8 mg maintained their extended 8-week dosing intervals through 36 weeks, and almost 70% had a last assigned dosing interval of 12 weeks."

EMA filing • Macular Edema • Retinal Vein Occlusion

Faricimab versus Aflibercept 8mg in the Treatment of Eyes Recalcitrant to Alternative Anti-VEGF Therapies (ARVO 2025) - "Purpose The most recently approved anti-vascular endothelial growth factor (anti-VEGF) injections faricimab (IVF; Vabysmo; South San Francisco, CA) and aflibercept 8mg (IVA; Eylea HD; Regeneron; Tarrytown, NY) supposedly offer the benefits of decreased treatment burden and improved effectivity when compared to prior agents. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Network meta-analyses (NMAs) of number of injections (NoI) with high-dose (HD) aflibercept (AFL) versus faricimab (FAR) in patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Initial functional and anatomical outcomes of high-dose aflibercept 8 mg in neovascular age-related macular degeneration (nAMD) (ARVO 2025) - "However, we found that a considerable portion of patients did not experience resolution of intraretinal and subretinal fluid and could not extend their treatment interval past the FDA recommended 8 ± 1 weeks after three initial injections. In contrast to clinical trial data which only studied treatment-naïve patients, this study highlights the real-world difficulties of managing chronic and treatment-resistant nAMD patients with aflibercept 8.0 mg."

Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

The Effect of Using High Dose Aflibercept 8mg in Treating Age-Related Macular Degeneration. (ARVO 2025) - "Most patients achieved a "dry" retina after one injection, suggesting fewer treatments might be needed. The therapy was safe and shows promise for improving vision while reducing treatment burden."

Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis • Wet Age-related Macular Degeneration

Real-World Functional and Anatomical Outcomes of High-Dose Aflibercept 8.0 mg in Diabetic Macular Edema (ARVO 2025) - "Notably, eyes that had previously been treated with other intravitreal injections were often able to extend their injection intervals, reducing the burden of frequent visits. These real-world findings provide valuable insight into the challenges of treating DME, especially in patients with chronic or treatment-resistant disease, and highlight differences from clinical trial data that included more controlled patient populations."

Clinical • Real-world • Real-world evidence • Diabetic Macular Edema • Ophthalmology

Volumetric Fluid Assessment Comparing High-Dose Aflibercept to Standard Dose Aflibercept in Neovascular Age-Related Macular Degeneration in the CANDELA Phase 2 Trial (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

P2 data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

ELARA: A Phase 3b, Single-Arm Study of Aflibercept 8 mg Dosed Every 4 Weeks in Adult Participants With Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME) (clinicaltrials.gov) - P3 | N=1118 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Efficacy and Safety of High-Dose Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration (nAMD): A Systematic Review. (PubMed, Cureus) - "There was a complication rate of 1.7% for serious adverse effects. In conclusion, higher doses of aflibercept (>2 mg) are safe and effective for treating nAMD, but further research is needed to analyse the comparison of different high doses and the effect of injection frequency on outcomes."

Journal • Review • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Clinical trials and real-world studies examining faricimab and high-dose aflibercept for wet age-related macular degeneration and diabetic macular edema. (PubMed, Curr Opin Ophthalmol) - "Both faricimab and high-dose aflibercept show promise in reducing treatment burden for wet age-related macular degeneration and diabetic macular edema through extended dosing intervals while maintaining or improving clinical outcomes compared to standard anti-VEGF therapy. Faricimab has demonstrated this both in clinical trials as well as real-world studies, while high-dose aflibercept has demonstrated similar durability in trials but requires additional real-world evidence."

Journal • Real-world evidence • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Initial Functional and Anatomical Outcomes of High-Dose Aflibercept 8 mg in Exudative Neovascular Age-Related Macular Degeneration. (PubMed, Ophthalmol Retina) - "HDA demonstrated stable BCVA and significant reductions in macular fluid during the follow-up period. A considerable proportion of patients were unable to extend treatment intervals to at least 8-weeks due to persistent macular fluid. These findings suggest that HDA maintains functional stability while improving anatomic outcomes, though real-world challenges in managing chronic nAMD may limit the ability to extend treatment intervals."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Bayer files for approval of extended 6-month treatment interval for Eylea 8 mg in the EU (Bayer Press Release) - "Bayer has submitted an application to the European Medicines Agency (EMA) to expand treatment intervals of up to 6 months with Eylea 8 mg (aflibercept 8 mg, 114.3 mg/ml solution for injection) for the treatment of two major retinal diseases, neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME). The submission is based on positive three-year results from open-label extension studies of the clinical trials PULSAR, in nAMD and PHOTON, in DME. In both extension studies patients randomized to Eylea 8 mg from baseline maintained their visual and anatomic improvements, with 28% of patients in DME and 24% of patients in nAMD having a last assigned dosing interval of 6 months at the end of three years."

EMA filing • Diabetic Macular Edema • Wet Age-related Macular Degeneration

EYLEA HD (aflibercept) Injection 8 mg Positive Phase 3 Results in Patients with Macular Edema following Retinal Vein Occlusion Presented at Angiogenesis Meeting (GlobeNewswire) - P3 | N=892 | QUASAR (NCT05850520) | Sponsor: Bayer | "The data were presented today at the virtual Angiogenesis (Angiogenesis, Exudation, and Degeneration) 2025 annual meeting and will support the submission of a supplemental Biologics License Application to the U.S. Food and Drug Administration (FDA) in the first quarter of 2025....The QUASAR trial met its primary endpoint at 36 weeks, with both groups of EYLEA HD patients dosed every 8 weeks achieving non-inferior visual acuity gains compared to those receiving EYLEA (aflibercept) Injection 2 mg dosed every 4 weeks....Furthermore, in patients treated with EYLEA HD through 36 weeks, 88% of patients were able to sustain an 8-week dosing regimen following 3 initial monthly doses, and 93% of patients maintained an 8-week dosing regimen after completing 5 initial monthly doses."

FDA filing • P3 data • Macular Edema • Retinal Vein Occlusion

Three-Year Results for EYLEA HD (aflibercept) Injection 8 mg in Patients with Wet Age-related Macular Degeneration Demonstrate Continued Durable Vision Gains and Anatomic Improvements with Extended Dosing Intervals (GlobeNewswire) - P3 | N=1,011 | PULSAR (NCT04423718) | Sponsor: Bayer | "The results were presented today at the virtual Angiogenesis (Angiogenesis, Exudation, and Degeneration) 2025 annual meeting....Of the EYLEA HD patients (n=375) who completed the full 3 years of treatment: Nearly 60% had a last assigned dosing interval of ≥4 months, with 40% and 24% having a last assigned dosing interval of ≥5 and 6 months, respectively, at the end of three years of treatment. Vision gains and anatomical improvements – including robust reductions in retinal thickness - that were achieved through year two were sustained through year three in the extension study....Of these patients who completed the extension study (n=186), vision and anatomic improvements were maintained after switching to EYLEA HD, with 79% and 43% having a last assigned dosing interval of ≥3 and ≥4 months, respectively, at week 156."

P3 data • Wet Age-related Macular Degeneration

DEUTERON: A Study to Learn About the Blood Levels of Aflibercept When High-dose Aflibercept is Injected in Both Eyes of Participants With Diabetic Macular Edema or Neovascular Age-related Macular Degeneration (clinicaltrials.gov) - P4 | N=51 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Regeneron Reports Fourth Quarter and Full Year 2024 Financial and Operating Results; Initiates Quarterly Dividend and Increases Total Share Repurchase Capacity to ~$4.5 Billion (GlobeNewswire) - "Fourth quarter 2024 Dupixent global net sales (recorded by Sanofi) increased 15% to $3.70 billion versus fourth quarter 2023; full year 2024 Dupixent global net sales increased 22% to $14.15 billion versus 2023; Fourth quarter 2024 U.S. net sales for EYLEA HD and EYLEA increased 2% versus fourth quarter 2023 to $1.50 billion, including $305 million from EYLEA HD; full year 2024 U.S. net sales for EYLEA HD and EYLEA increased 1% versus 2023 to $5.97 billion versus 2023, including $1.20 billion from EYLEA HD."

Sales • Asthma • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Chronic Spontaneous Urticaria • Macular Edema • Wet Age-related Macular Degeneration

Regeneron Reports Fourth Quarter and Full Year 2024 Financial and Operating Results; Initiates Quarterly Dividend and Increases Total Share Repurchase Capacity to ~$4.5 Billion (GlobeNewswire) - "Key Pipeline Progress - EYLEA HD (aflibercept) 8 mg: The Company plans to submit a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2025. A regulatory application for a pre-filled syringe was submitted to the FDA, with an FDA decision expected by mid-2025. Dupixent (dupilumab): The FDA accepted for review the resubmission of an sBLA for Dupixent to treat adults and adolescents aged 12 years and older with chronic spontaneous urticaria (CSU) whose disease is not adequately controlled with H1 antihistamine treatment, with a target action date of April 18, 2025."

FDA approval • FDA filing • PDUFA • Chronic Spontaneous Urticaria • Macular Edema

DEUTERON: A Study to Learn About the Blood Levels of Aflibercept When High-dose Aflibercept is Injected in Both Eyes of Participants With Diabetic Macular Edema or Neovascular Age-related Macular Degeneration (clinicaltrials.gov) - P4 | N=45 | Recruiting | Sponsor: Bayer | Trial primary completion date: Mar 2026 ➔ Oct 2025 | Trial completion date: Mar 2026 ➔ Oct 2025

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

PHOTONiC: A Study to Learn More About How Well 8 Milligram Aflibercept Works and How Safe it is in Chinese Participants With Diabetic Macular Edema (clinicaltrials.gov) - P3 | N=333 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting | Trial primary completion date: May 2026 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Diabetic Macular Edema • Ophthalmology

High dose aflibercept treatment in naive neovascular age-related macular degeneration. (PubMed, Int Ophthalmol) - "High-dose Aflibercept of 4 mg/0.1 mL application with the TREX regimen was found to be efficient and safe. High-dose may also help to reduce the frequency of injections and visits in the follow-up period in eyes with nAMD. Prospective studies with large series are warranted."

Journal • Retrospective data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

ELARA: A Phase 3b, Single-Arm Study of Aflibercept 8 mg Dosed Every 4 Weeks in Adult Participants With Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME) (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=400 ➔ 1000

Enrollment change • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Regeneron Provides Business Updates and Highlights from Broad Clinical Pipeline at the 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Based on preliminary (unaudited) results, the products achieved 1% year-over-year growth by reaching $6 billion in aggregate U.S. net product sales for the year and $1.5 billion in aggregate U.S. net product sales for the fourth quarter of 2024, despite increasing competition. EYLEA HD U.S. net product sales were $305 million in the fourth quarter of 2024. EYLEA U.S. net product sales were $1.19 billion in the fourth quarter of 2024...The Company filed an application with the FDA for use of the EYLEA HD pre-filled syringe (PFS) with U.S. approval and launch expected by mid-2025. Longer term data in wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) are under FDA review with a PDUFA date of April 20, 2025 to potentially extend dosing intervals for EYLEA HD up to every-24 weeks."

Launch US • PDUFA • Sales • Age-related Macular Degeneration • Diabetic Macular Edema • Glaucoma • Macular Edema • Wet Age-related Macular Degeneration