Regulatory & Policy

Outlook Therapeutics to resubmit Lytenava BLA for wAMD after FDA appeal win

Outlook Therapeutics (Nasdaq: OTLK), based in Iselin, New Jersey, plans to resubmit a Biologics License Application (BLA) to the US FDA for Lytenava (bevacizumab-vikg) in neovascular age-related macular degeneration (nAMD), after the Outlook Therapeutics appeal of a Complete Response Letter was resolved in the company's favor through the FDA's Formal Dispute Resolution process.

The company said the resubmission is expected in June 2026 and is anticipated to be classified as a Class 1 resubmission, which carries a 60-day review window. A PDUFA date is expected within 60 days of the FDA's receipt of the resubmission. The filing seeks approval for Lytenava as an intravitreal injection for the treatment of nAMD. The FDA's Office of New Drugs concluded, through the formal dispute resolution process, that substantial evidence of effectiveness has been established for Lytenava in this indication, and directed the Division of Ophthalmology and Office of Specialty Medicine to work with Outlook Therapeutics to finalize labeling.

The evidence package supporting the BLA centers on two Phase III trials: NORSE TWO, the pivotal study, and NORSE EIGHT (NCT06190093), a confirmatory Phase III study. The FDA's Office of New Drugs determined that results from NORSE TWO, together with confirmatory evidence from NORSE EIGHT, natural history data, and mechanistic and pharmacodynamic data, collectively establish the required evidentiary standard. NORSE TWO met its primary endpoint of patients gaining three lines, or 15 letters, of visual acuity, along with key secondary endpoints including mean change from baseline in visual acuity. NORSE EIGHT, which used a primary endpoint of mean change from baseline in best-corrected visual acuity at week 8 in comparison to ranibizumab, did not meet that endpoint, though the FDA accepted it as part of the broader confirmatory evidence package.

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Bevacizumab-vikg is a recombinant humanized monoclonal antibody that neutralizes VEGF by sterically blocking its binding to VEGFR-1 and VEGFR-2 on endothelial cells, reducing neovascularization and vascular leakage in the retina following intravitreal injection. The nAMD treatment landscape includes faricimab (Vabysmo, Genentech/Roche), approved in 2022 as a bispecific antibody targeting both VEGF-A and angiopoietin-2, and aflibercept 8 mg (Eylea HD, Regeneron), approved in 2023, both of which offer extended dosing intervals. Lytenava does not introduce a new mechanism but would, if approved, become the first FDA-approved ophthalmic formulation of bevacizumab, converting a high-volume off-label clinical practice — compounded intravitreal bevacizumab is already among the most widely used anti-VEGF agents globally due to its low cost — into a regulated, labeled therapy with an FDA-approved manufacturing process and pharmacovigilance framework. Lytenava already holds marketing authorization in the EU and UK for wet AMD, where it is commercially available in Germany, Austria, and the UK.


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