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

Prospective Trial of the Efficacy and Safety of a Personalized Regimen of High-dose Aflibercept 8mg on Treatment-naive Polypoidal Choroidal Vasculopathy: the PALLAS Trial (clinicaltrials.gov) - P3 | N=50 | Recruiting | Sponsor: Yeungnam University College of Medicine

New P3 trial • Age-related Macular Degeneration

Evercore ISI raises Regeneron stock price target to $875 on Dupixent growth (Investing.com) - "The research firm cited Dupixent’s continued growth trajectory and the upcoming Eylea HD, which is expected to compete more effectively with a prefilled syringe launch anticipated in the second quarter of 2026."

Launch US • Stock price • Asthma • Atopic Dermatitis • Bullous Pemphigoid • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Diabetic Macular Edema • Diabetic Retinopathy • Eosinophilic Esophagitis • Immunology • Prurigo Nodularis • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

Antibody-based therapeutics and therapeutic development for diabetic retinopathy: targeting VEGF, Ang/Tie, and inflammatory pathways. (PubMed, Front Endocrinol (Lausanne)) - "Recent clinical innovations include ophthalmic formulations of bevacizumab, high-dose aflibercept, the ranibizumab port delivery system, and bispecific antibodies like faricimab that simultaneously target VEGF and angiopoietin-2 pathways, alongside emerging preclinical investigations into novel targets and bio-engineered delivery platforms. Despite therapeutic advances, significant challenges persist, including cost-effectiveness concerns, treatment burden, and adherence issues. This review highlights the transformative impact of mAb therapy in DR management while acknowledging the need for continued innovation to address existing limitations and optimize patient outcomes through personalized treatment approaches."

Journal • Review • Diabetes • Diabetic Retinopathy • Macular Edema • Metabolic Disorders • Ophthalmology • Retinal Disorders • IL17A • IL1B • IL6

The European Commission has granted marketing authorization in the European Union (EU) for Eylea 8 mg (aflibercept 8 mg, 114.3 mg/ml solution for injection) for the treatment of patients with visual impairment due to macular edema following retinal vein occlusion (RVO) including branch, central and hemiretinal vein occlusion (Bayer Press Release) - "RVO is the third indication for Eylea 8 mg....In the QUASAR trial, Eylea 8 mg achieved non-inferior functional and anatomic outcomes compared to Eylea 2 mg, with three times fewer patients requiring monthly intervals (every 4 weeks), despite patients in all treatment arms having the option to extend dosing intervals."

EMA approval • Macular Edema • Retinal Vein Occlusion

Key Pipeline Progress: EYLEA HD (aflibercept) 8 mg (Regeneron Pharmaceuticals Press Release) - "In December 2025, the Company submitted a regulatory application to the FDA to include a new manufacturer to fill pre-filled syringes for EYLEA HD. An FDA decision is expected in the second quarter of 2026."

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

EYLEA HD (aflibercept) Injection 8 mg Presentations at Angiogenesis 2026 Underscore Strength of its Clinical Profile for the Treatment of Serious Retinal Diseases (GlobeNewswire) - "New presentations include final 64-week results from the Phase 3 QUASAR trial in patients with retinal vein occlusion, as well as full primary results from the Phase 3b ELARA trial in patients treated with monthly dosing."

Clinical data • Age-related Macular Degeneration • Diabetic Macular Edema • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

...Eylea outlook and 2026 catalysts (Streetinsider.com) - "Ahmad pointed to a busy 2026 catalyst calendar, including the 'LAG3 readout in 1H26,' an expected Eylea HD PFS approval 'mid-2026,'..."

Approval • P3 data • Diabetic Macular Edema • Diabetic Retinopathy • Melanoma • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

Bayer Korea announced that its Eylea pre-filled syringe 8mg will be covered by health insurance starting Jan. 1 (Korea Biomedical Review) - "According to the Ministry of Health and Welfare notice, coverage applies to patients with submacular choroidal neovascularization caused by age-related macular degeneration. It also covers diabetic macular edema patients who meet specific criteria, including hemoglobin A1C levels of 10 percent or less and a central retinal thickness of at least 300 micrometers....In the PULSAR and PHOTON clinical trials, Eylea 8mg demonstrated visual acuity improvement and safety profiles non-inferior to the 2mg dose."

Reimbursement • Age-related Macular Degeneration • Diabetic Macular Edema

Bilateral Sterile Intraocular Inflammation Following Intravitreal Aflibercept 8 mg Injections: A Case Report. (PubMed, Reports (MDPI)) - "Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management."

Journal • Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Pain • Retinal Disorders • Wet Age-related Macular Degeneration

Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: Post Hoc Analysis of the PULSAR Randomized Clinical Trial. (PubMed, JAMA Ophthalmol) - P3 | "In the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) phase 3 randomized clinical trial, treatment with aflibercept, 8 mg, demonstrated noninferior (4-letter margin) best-corrected visual acuity (BCVA) gains vs aflibercept, 2 mg, in participants with neovascular age-related macular degeneration (nAMD)...Results of this post hoc analysis of the PULSAR randomized clinical trial in participants with PCV demonstrated similar visual and anatomic outcomes with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting the use of aflibercept, 8 mg, as an alternative monotherapy for PCV. ClinicalTrials.gov Identifier: NCT04423718."

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

High-Dose Aflibercept for PCV-Toward Potentially Extended Durability. (PubMed, JAMA Ophthalmol) - No abstract available

Journal

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