FDA Accepts Alvotech/Teva’s Application for Eylea Biosimilar

The FDA has accepted for review a biologics license application (BLA) for AVT06, Alvotech’s proposed biosimilar to Regeneron’s Eylea (aflibercept), a biologic used to treat eye disorders. Companies officials expect the regulatory approval to be completed in the fourth quarter of 2025, according to a news release.

Alvotech and Teva Pharmaceuticals have partnered for the development of AVT06, a biosimilar candidate Eylea 2 mg; Alvotech is currently also developing AVT29, a biosimilar candidate for Eylea HD 8 mg. AVT06/AVT29 is a recombinant fusion protein and a biosimilar candidate to Eylea. Aflibercept works by inhibiting vascular endothelial growth factor (VEGF), which prevents abnormal blood vessel growth within the eye. By blocking VEGF, aflibercept products can slow down or reduce damage to the retina and help preserve vision.

Eylea is approved to patients with neovascular (wet) age-related macular degeneration (AMD), macular edema, and diabetic retinopathy. The low dose form of Eylea is also approved to treat patients with retinopathy of prematurity (ROP) and macular edema after retinal vein occlusion, a blockage in a small blood vessel that carries blood away from the retina. Retinal vein occlusion is a common cause of vision loss in adults and the second most common retinal vascular disease.

In 2024, U.S. sales of Eylea (low dose and HD combined) were $4.77 billion. Eylea 2 mg has a list price of $1,896.25 for a single dose glass vial. Eylea HD 8 mg has a cost of $2,625.

In January 2024, Alvotech announced positive top-line results from a confirmatory clinical study comparing the efficacy, safety, and immunogenicity of AVT06. The study met its primary endpoint, with results demonstrating therapeutic equivalence and comparable safety beteween AVT06 and Eylea. The AVT06-GL-C01 confirmatory study compared AVT06 with Eylea in patients with neovascular (wet) AMD. The primary outcome measure was change from baseline to week 8 in best-corrected visual acuity (BCVA). The study met its primary endpoint, with results demonstrating therapeutic equivalence between Alvotech’s biosimilar candidate and Eylea.

Related: FDA Approves First Interchangeable Biosimilars to Eylea

So far, five biosimilars that reference Eylea 2 mg have been approved by the FDA. The first biosimilars were approved in May 2024: Biocon Biologic’s Yesafili (aflibercept-jbvf) and Samsung Bioepis’ Opuviz (aflibercept-yszy) are approved to treat neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy. A third biosimilar was approved in June 2024: Formycon’s Ahzantive (aflibercept-mrbb).

Two additional biosimilars that reference Eylea were approved in August 2024: Sandoz’s Enzeevu (aflibercept-abzv) and Amgen’s Pavblu (aflibercept-ayyh). Pavblu has already launched, despite ongoing patent litigation and has a list price of $1,664, according to AIS Health, an MMIT company.

Regeneron continues research of Eylea HD. In December 2024, the company released data from the phase 3 QUASAR trial investigating Eylea HD 8 mg to treat patients with macular edema following retinal vein occlusion.

In this trial, patients dosed with Eylea every 8 weeks achieving non-inferior visual acuity gains compared with those receiving Eylea 2 mg dosed every 4 weeks. Ocular treatment-emergent adverse events occurring in ≥5% of all Eylea HD patients included increased ocular pressure (5%); there was one case each of endophthalmitis and retinal vasculitis.

Regeneron plans to submit a supplement BLA in the first quarter of 2025 for Eylea HD for this indication.

Additionally, Regeneron has filed an application with the FDA for use of the Eylea HD E pre-filled syringe (PFS) with U.S. approval and launch expected by mid-2025.