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

Sterile Intraocular Inflammation in Patients Receiving Both Faricimab and High-Dose Aflibercept in Consecutive Order. (PubMed, J Vitreoretin Dis) - "Shortly after, each patient developed an episode of IOI. Patients receiving different high-dose or longer-acting agents in short order may be at risk for developing antidrug antibodies and IOI."

Journal • Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

Bayer Korea said it has received approval from the Ministry of Food and Drug Safety for a pre-filled syringe (PFS) formulation of Eylea 8mg (ingredient: aflibercept), expanding treatment options for patients with vision-threatening retinal diseases. (Korea Biomedical Review) - "The newly approved pre-filled syringe shares the same indications as the existing Eylea 8mg vial, namely for the treatment of vision loss caused by neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)...Eylea 8mg has been recognized as a game changer in retinal disease management, demonstrating equivalent efficacy and safety to the long-established Eylea 2mg in the pivotal PULSAR and PHOTON trials."

Korea approval • Age-related Macular Degeneration • Diabetic Macular Edema

A Comparative Assessment of Intraocular Pressure Changes After Aflibercept 8 mg and Faricimab-svoa Intravitreal Injections in Wet Age-Related Macular Degeneration. (PubMed, Cureus) - "Formulations with higher concentrations, such as aflibercept 8 mg (Eylea HD; Bayer AG, Leverkusen, Germany), which are administered in larger volumes, may raise concerns about potential increases in intraocular pressure (IOP) and other ocular complications...The research recorded lens condition, the need for paracentesis, and the application of Iopidine drops...Conclusions Intravitreal injections of aflibercept 8 mg and faricimab-svoa caused a small and temporary increase in IOP and there were no cases requiring urgent management. Our results confirm the short-term ocular safety of aflibercept 8 mg and faricimab-svoa for the treatment of WetAMD and highlight the need for individualized monitoring for patients at risk of increased IOP."

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

Aflibercept 8 Mg Shows Long-Term Efficacy In Diabetic Macular Edema With Fewer Injections, Shows Trial (Medical Dialogues) - "The longer-term data among Aflibercept 8 mg who completed the trial demonstrated that the vast majority of patients were able to maintain or further extend these dosing intervals through two years with: 89% maintaining ≥12-week dosing intervals through two years, compared to 93% through one year (48 weeks); 83% maintaining ≥16-week dosing intervals through two years, compared to 89% maintaining a 16-week dosing interval through one year; 43% meeting the criteria for ≥20-week dosing intervals by week 96, including 16% and 27% who were eligible for 20- and 24-week dosing intervals, respectively."

P2/3 data • Diabetic Macular Edema

High Dose (HD) Aflibercept Switch in Neovascular Age-related Macular Degeneration (nAMD): to Load or Maintain (HEIRLOOM) (clinicaltrials.gov) - P3 | N=180 | Not yet recruiting | Sponsor: Clinique de Retine de l'est

New P3 trial • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

...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. (GlobeNewswire) - "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."

FDA approval • Macular Edema • Retinal Vein Occlusion

HERO: High Dose Eylea for Proliferative Diabetic Retinopathy Outcomes (clinicaltrials.gov) - P4 | N=40 | Not yet recruiting | Sponsor: Edward Wood, MD

New P4 trial • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

High Dose Aflibercept in Diabetic Macular Edema in Patients With Previous Vitrectomy (clinicaltrials.gov) - P4 | N=15 | Recruiting | Sponsor: Retina Consultants of Orange County | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2027 ➔ Aug 2027 | Initiation date: Nov 2024 ➔ Jul 2025 | Trial primary completion date: Mar 2026 ➔ Aug 2026

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Diabetic Macular Edema • Ophthalmology

Transition to high-dose aflibercept and intraocular pressure risk: A two-step approach to injection volume at Oslo University Hospital. (PubMed, Acta Ophthalmol) - No abstract available

Journal

Regeneron Reports Second Quarter 2025 Financial and Operating Results (GlobeNewswire) - "Dupixent global net sales (recorded by Sanofi) increased 22% to $4.34 billion; EYLEA HD U.S. net sales increased 29% to $393 million; total EYLEA HD and EYLEA U.S. net sales decreased 25% to $1.15 billion....The Company now expects regulatory approvals to be delayed for its currently pending FDA applications for EYLEA HD (pre-filled syringe, every-four-week dosing, and for the treatment of macular edema following retinal vein occlusion), which have PDUFA dates in August 2025. The anticipated delay is related to observations from an FDA general site inspection at the filler for EYLEA HD in these regulatory applications, Catalent Indiana LLC (recently acquired by Novo Nordisk A/S). This inspection was completed in mid-July and was not specific to EYLEA HD. Novo has been in communication with the FDA and expects to submit its response next week."

FDA event • Sales • Asthma • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Chronic Spontaneous Urticaria • Diabetic Macular Edema • Eosinophilic Esophagitis • Macular Edema • Prurigo Nodularis • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

Outcomes of and Surgical Technique for Treatment With High-Dose Aflibercept. (PubMed, J Vitreoretin Dis) - " A prospective pilot study was performed to analyze the short-term safety and visual gain (expressed in logMAR), including increase in intraocular pressure (IOP), resulting from a modified regimen consisting of 0.18 mL paracentesis followed by an intravitreal injection of 0.18 mL aflibercept (prefilled syringe), 0.20 mL aflibercept (vial), or 0.22 mL ziv-aflibercept (compounded). In 2 eyes (6.3%), reflux as a tiny bleb was noted. When high-dose aflibercept is neither available nor affordable, a patient's readily accessible and cost-effective regimen of aflibercept will allow an exact delivery of high-dose aflibercept, combining minimal drug reflux, minimal immediate increase in IOP, and potential clinical efficacy in the short term."

Journal • Age-related Macular Degeneration • Hematological Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

EU Approves Bayer’s Eylea 8 Mg For Extended 6-Month Dosing In Retinal Diseases (Nasdaq) - "Baye...announced that the European Commission has granted a label extension in the European Union for Eylea 8 mg (aflibercept 8 mg, 114.3 mg/ml solution for injection) with extended treatment intervals of up to 6 months for the treatment of two major retinal diseases, neovascular (wet) age-related macular degeneration (nAMD) and visual impairment due to diabetic macular edema (DME)...Eylea 8 mg is being jointly developed by Bayer and Regeneron. Regeneron maintains exclusive rights to Eylea 2 mg and Eylea HD in the United States. Bayer has licensed the exclusive marketing rights outside the United States, where the companies share equally the profits from sales of Eylea 2 mg and Eylea 8 mg."

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

Eylea 8 mg approved in China for wet age-related macular degeneration (Bayer Press Release) - "The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has approved Eylea 8 mg (aflibercept 8 mg) for the treatment of neovascular (wet) age-related macular degeneration (nAMD) in China. The approval is based on positive results from the Phase III PULSAR trial at week 48, which demonstrated comparable efficacy and safety of Eylea 8 mg with treatment intervals of 3 or 4 months (12 or 16 weeks) compared to standard of care Eylea 2 mg (aflibercept 2 mg) with a fixed bi-monthly (every 8 weeks) interval."

China approval • Wet Age-related Macular Degeneration

Bayer Gets CHMP Nod for Eylea 8 mg in the EU for 2 Major Eye Diseases (Yahoo Finance) - "Bayer...announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the label extension for Eylea 8 mg (aflibercept) in the EU...This extension will enable longer treatment intervals, up to six months, for two major retinal conditions, neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME), pending approval by the European Commission...A decision is anticipated in the coming weeks....The favorable CHMP opinion is supported by positive three-year results from Bayer’s open-label extension studies of the pivotal PULSAR study for nAMD and the PHOTON study for DME."

CHMP • Diabetic Macular Edema • Wet Age-related Macular Degeneration

Aflibercept 8 mg to treat macular edema following retinal vein occlusion submitted for approval in Japan (Bayer Press Release) - "Bayer has submitted an application to the Japanese Ministry of Health, Labour and Welfare (MHLW) 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. In Japan, this would be the third indication for aflibercept 8 mg supporting the blockbuster status of Eylea. The submission to the MHLW is supported by favorable outcomes from the global randomized, double-masked, active-controlled phase III QUASAR study."

Japan filing • Retinal Vein Occlusion

Regeneron Reports First Quarter 2025 Financial and Operating Results (GlobeNewswire) - "First quarter 2025 Dupixent global net sales (recorded by Sanofi) increased 19% to $3.67 billion versus first quarter 2024; First quarter 2025 EYLEA HD U.S. net sales increased 54% to $307 million versus first quarter 2024; total EYLEA HD and EYLEA U.S. net sales decreased 26% to $1.04 billion."

Sales • Age-related Macular Degeneration • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Diabetic Retinopathy • Macular Edema • Nasal Polyps • 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 | Trial completion date: May 2027 ➔ Jan 2027 | Trial primary completion date: Dec 2025 ➔ Aug 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

EYLEA HD (aflibercept) Injection 8 mg Presentations at ARVO Reinforce Continued Safety and Efficacy and Highlight Early Real-World Outcomes for Patients with Serious Retinal Disease (GlobeNewswire) - "Regeneron Pharmaceuticals...announced the upcoming presentation of 27 abstracts, including eight oral presentations on EYLEA HD (aflibercept) Injection 8 mg in wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and diabetic retinopathy (DR). Among the new results and analyses are initial insights on the real-world use of EYLEA HD in clinical practice, which reinforce the outcomes seen in pivotal trials. These data will be presented at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting..."

Clinical data • Real-world • Diabetic Macular Edema • Diabetic Retinopathy • Wet Age-related Macular Degeneration

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