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

High-Dose 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration: Who Is Being Treated with This New Agent? (PubMed, Life (Basel)) - "The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases...The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept."

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

Regeneron Pharmaceuticals…announced that the U.S. Food and Drug Administration (FDA) has approved EYLEA HD (aflibercept) Injection 8 mg for the treatment of patients with macular edema following retinal vein occlusion (RVO) with up to every 8-week dosing after an initial monthly dosing period (GlobeNewswire) - "The FDA also approved an every 4-week (monthly) dosing option for some patients who may benefit from resuming this dosing schedule across approved indications: wet age-related macular degeneration (wAMD), diabetic macular edema (DME), diabetic retinopathy (DR) and RVO....The FDA approval for the treatment of RVO is based on data from the Phase 3 QUASAR trial..."

FDA approval • Diabetic Macular Edema • Diabetic Retinopathy • Retinal Vein Occlusion • 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 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

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

Net product sales of EYLEA HD increased in the third quarter of 2025, compared to the third quarter of 2024, due to higher sales volumes driven by increased demand, partly offset by a lower net selling price. (The Manila Times) - "Net product sales of EYLEA in the third quarter of 2025, compared to the third quarter of 2024, were negatively impacted by (i) lower sales volumes as a result of continued competitive pressures, loss in market share to compounded bevacizumab due to patient affordability constraints, and the continued transition of patients to EYLEA HD, and (ii) a lower net selling price."

Commercial • Diabetic Retinopathy • Inflammation • Wet Age-related Macular Degeneration

In October 2025, the Company was notified by Catalent Indiana, LLC (Catalent), the manufacturing filler in the EYLEA HD Biologics License Application (BLA), that they received an official action indicated (OAI) letter from the FDA citing unresolved issues related to a July 2025 FDA general site inspection (not specific to EYLEA HD). (GlobeNewswire) - "Yesterday, the FDA issued a Complete Response Letter (CRL) for the pre-filled syringe supplemental BLA (sBLA).The sole approvability issue cited in the CRL relates to unresolved inspection findings at Catalent. The Company is planning to submit by January 2026 an application to include a new pre-filled syringe manufacturing filler in the EYLEA HD BLA."

CRL • FDA filing • Diabetic Macular Edema • Wet Age-related Macular Degeneration

There is also an sBLA under review by the FDA for EYLEA HD every-four-week dosing and for the treatment of macular edema following retinal vein occlusion (RVO), which has a target action date in late November 2025. (GlobeNewswire) - "In addition, the Company has submitted an application to include an additional vial filler, with an FDA decision regarding this new vial filler expected by late December 2025."

PDUFA • Macular Edema • Retinal Vein Occlusion

EYLEA HD U.S. net sales increased 10% to $431 million; total EYLEA HD and EYLEA U.S. net sales decreased 28% to $1.11 billion (GlobeNewswire)

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

Aflibercept 8 mg Shows Promise in Reducing Injection Burden | AAO 2025 (Managed Healthcare Executive) - "The data revealed that aflibercept 8 mg showed promise in treatment-naive patients, allowing them to go up to 12 weeks between injections...Do also explained that while the standard 2 mg dose of aflibercept has been safe and effective for over a decade, the 8 mg dose could offer longer-lasting results. This could mean fewer injections for patients and less strain on clinics....In addition, she shared that giving patients the right therapy early is key to preserving and improving vision."

Real-world • Age-related Macular Degeneration • Diabetic Macular Edema

Real-World Functional and Anatomic Outcomes With Aflibercept 8.0 mg in Patients With Diabetic Macular Edema. (PubMed, J Vitreoretin Dis) - "Purpose: To assess clinical outcomes in diabetic macular edema (DME) patients treated with high-dose aflibercept 8.0 mg (HDA), focusing on treatment intervals, anatomic changes, and best-corrected visual acuity (BCVA)... HDA reduced CST and stabilized BCVA in DME patients. However, remaining challenges include frequent injections and persistent macular fluid, underscoring the chronic, treatment-resistant nature of DME and need for optimized treatment strategies."

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

Faricimab at 6 and 12 mg reduces pigment epithelium detachment in treatment-resistant macular neovascularization: an OCT and AI analysis. (PubMed, Sci Rep) - "In MNV eyes resistant to high-dose Aflibercept, Faricimab 6 mg provides meaningful anatomical improvement, particularly in PED volume. However, escalating Faricimab to 12 mg offers no additional benefit, suggesting therapeutic saturation at the standard dose."

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

Aflibercept (Eylea) 8mg for nAMD. HTA ID: 25054 (National Centre for Pharmacoeconomics, Ireland) - "Indication: Aflibercept (Eylea) 8mg is indicated for the treatment of neovascular (wet) age-related macular degeneration (nAMD) in adults....Rapid review outcome: A full HTA is not recommended. The NCPE recommends that aflibercept (Eylea) 8mg not be considered for reimbursement at the submitted price."

Reimbursement • Wet Age-related Macular Degeneration

Bayer seeks EMA approval for Aflibercept for retinal vein occlusion treatment (Medical Dialogues) - "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."

EMA filing • Retinal Vein Occlusion

Recalcitrant Peripapillary Pachychoroid Syndrome Responds to High-Dose Aflibercept Therapy. (PubMed, Retin Cases Brief Rep) - "High-dose intravitreal aflibercept therapy may lead to remarkable anatomical and functional improvement in eyes with recalcitrant PPS."

Journal • Macular Edema • Ophthalmology

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