Outlook Therapeutics Seeks FDA Meeting After Second CRL for ONS-5010
Outlook Therapeutics has submitted a Type A meeting request to the U.S. Food and Drug Administration (FDA) after receiving a second complete response letter (CRL) regarding its biologics license application (BLA) for ONS-5010 (bevacizumab-vikg). The investigational therapy is being developed for the treatment of wet age-related macular degeneration (AMD).
ONS-5010 is a recombinant humanized monoclonal antibody that selectively binds to all isoforms of vascular endothelial growth factor (VEGF) with high affinity. It neutralizes VEGF activity by sterically blocking its interaction with VEGFR-1 (Flt-1) and VEGFR-2 (KDR) on endothelial cells.
Clarifying FDA Requirements
The Type A meeting is intended to clarify the confirmatory efficacy evidence requested by the FDA in the CRL issued on August 27, 2025. The agency noted that ONS-5010 did not meet the primary efficacy endpoint in the NORSE EIGHT trial and therefore recommends the submission of additional confirmatory data to support the application. However, the FDA acknowledged that the NORSE TWO pivotal trial did meet its safety and efficacy endpoints.
Outlook Therapeutics resubmitted the BLA in February 2025, and it was accepted by the FDA in April 2025. The resubmission was based on NORSE EIGHT clinical trial results and additional chemistry, manufacturing, and controls (CMC) data as requested by the agency.
Company Perspective
Commenting on the request, Bob Jahr, CEO of Outlook Therapeutics, stated:
“We believe this Type A meeting will provide us with additional clarity on the FDA’s requirements to remedy the deficiency identified in the CRL. The Outlook Therapeutics team remains dedicated to our mission to provide patients in the US with a safe and effective alternative to compounded bevacizumab, which has been used off-label as a first-line treatment for wet-AMD for years despite concerns around potency, sterility, consistency, and regulatory oversight associated with the use of compounded products.”
Progress in Europe
Despite regulatory hurdles in the U.S., Outlook Therapeutics has seen positive momentum in Europe. In March 2024, the European Medicines Agency (EMA) issued a positive CHMP opinion on ONS-5010. Subsequently, in June 2025, the product, marketed under the name LYTENAVA (bevacizumab gamma), became commercially available in Germany and the UK for the treatment of wet AMD.
