FDA Approves Pavblu, Fifth Biosimilar to Eylea, for Retinal Conditions
核心洞察
The FDA has approved Pavblu (aflibercept-ayyh) as a biosimilar to Eylea (aflibercept) for treating retinal conditions..
Pavblu's approval was based on a Phase 3 study demonstrating similar safety and efficacy to Eylea in patients with wet AMD.
Amgen and Regeneron are engaged in a legal dispute concerning Pavblu, with a court decision pending on potential launch restrictions.
The FDA has approved Pavblu (aflibercept-ayyh), marking the fifth biosimilar referencing Eylea (aflibercept), for the treatment of several retinal conditions including neovascular age-related macular degeneration (搜索) (wet AMD), macular edema (搜索) following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy (搜索). Developed by Amgen, Pavblu's approval follows a randomized, double-masked, phase 3 study demonstrating its biosimilarity to Eylea.
Clinical Trial Data Supporting Approval
The approval of Pavblu was supported by data from a Phase 3 clinical trial (NCT04270747) that enrolled 566 patients across 126 global sites. The study compared the safety and efficacy of Pavblu (ABP 938) with Eylea in patients with wet AMD. Participants were randomized 1:1 to receive 2 mg (0.05 mL) intravitreally of either ABP 938 or aflibercept. The primary endpoint, evaluated at week 8, measured the change in best corrected visual acuity using the early treatment diabetic retinopathy (搜索) study letter score from baseline. The study found no clinically meaningful differences between Pavblu and Eylea, thus establishing biosimilarity.
Study Design and Results
The study included a screening period of up to 4 weeks, followed by 48 weeks of treatment and a safety follow-up through week 52, for a total study duration of up to 56 weeks. At week 16, subjects were re-randomized in a masked manner. Subjects initially assigned to ABP 938 continued receiving ABP 938 via intravitreal injection every 8 weeks from week 16 to week 48. Subjects initially assigned to reference aflibercept were re-randomized in a 1:1 ratio to either continue on the reference product or switch to ABP 938, receiving IVT injections every 8 weeks from week 16 to week 48. The study's final cohort included 576 patients from 102 centers across multiple countries, with a majority of the patients being women and 86% being White.
Legal Challenges and Market Implications
Amgen and Regeneron, the maker of Eylea, are currently involved in a Biologics Price Competition and Innovation Act lawsuit regarding Pavblu. Regeneron alleges that Amgen infringed 32 patents covering the manufacturing and use of Eylea when developing Pavblu. A preliminary injunction hearing was held on August 13, 2024, to determine whether Amgen will be blocked from launching Pavblu at-risk; the court’s decision is still pending. Regeneron has filed similar lawsuits against other biotech companies attempting to develop Eylea biosimilars.
Mechanism of Action and Indications
The active ingredient in Pavblu is aflibercept, a recombinant fusion protein that inhibits vascular endothelial growth factor (VEGF (搜索)) to prevent abnormal blood vessel growth in the eye. Pavblu is indicated for neovascular (wet) age-related macular degeneration (搜索) (AMD), macular edema (搜索) following retinal vein occlusion (RVO), diabetic macular edema (DME), and diabetic retinopathy (搜索) (DR).
Safety Information
Key contraindications for Pavblu include ocular or periocular infection, active intraocular inflammation, and hypersensitivity. Warnings and precautions include the risk of endophthalmitis, retinal detachments, retinal vasculitis, increases in intraocular pressure, and potential arterial thromboembolic events. The most common adverse reactions (≥5%) reported in patients receiving aflibercept were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.