Outlook Therapeutics requests Type A meeting with FDA following second CRL for ONS-5010

According to Outlook, the Type A meeting seeks to clarify details of the confirmatory evidence required by the FDA in the CRL issued August 27, 2025. Image credit: AdobeStock/metamorworks

Outlook Therapeutics has requested a Type A meeting with the US Food and Drug Administration following the agency issuing a complete response letter (CRL) to its biologics license application (BLA) resubmission for ONS-5010 (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (AMD).^1,2

Bevacizumab-vikg is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human VEGF and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells.

According to Outlook, the Type A meeting seeks to clarify details of the confirmatory evidence required by the FDA in the CRL issued August 27, 2025. In the CRL, the FDA advised that, because ONS-5010 did not meet the primary efficacy endpoint in NORSE EIGHT, it is recommended that confirmatory evidence of efficacy be submitted to support the application for ONS-5010. In the CRL, the FDA did acknowledge the NORSE TWO pivotal trial met its safety and efficacy endpoints.

The company previously resubmitted the BLA in February 2025, and the FDA accepted the resubmission in April 2025.³ The BLA resubmission was based on the efficacy and safety demonstrated in the NORSE EIGHT clinical trial, as well as additional CMC information requested by the FDA

Bob Jahr, CEO of Outlook Therapeutics, commented on the request, saying, “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.”

This is the second Type A meeting requested by Outlook regarding ONS-5010 and the second CRL issued by the FDA for ONS-5010.⁴ The first Type A meeting request in September 2023 followed the first CRL issued on August 29, 2023. For the 2023 submission, it was noted that the FDA “could not approve the BLA during the review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.”

After the CRL in 2023, Outlook Therapeutics stock underwent a 1-for-20 reverse stock split as “part of the Company’s plan to regain compliance with the minimum bid price ($4 per share) requirement for continued listing on the Nasdaq Capital Market.”⁵

In March 2024, the European Medicines Agency (EMA) issued a positive Committee for Medicinal Products for Human Use (CHMP) opinion on ONS-5010. In June 2025, LYTENAVA (bevacizumab gamma) became commercially available in Germany and the UK for the treatment of wet AMD.

References:

1. Outlook Therapeutics Requests Type A Meeting with FDA. Published September 2, 2025. Accessed September 3, 2025. https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeutics-requests-type-meeting-fda

2. Harp MD. FDA issues complete response letter to Outlook Therapeutics for resubmitted BLA for ONS-5010. Published August 28, 2025. Accessed September 3, 2025. https://www.ophthalmologytimes.com/view/fda-issues-complete-response-letter-to-outlook-therapeutics-for-resubmitted-bla-for-ons-5010

3. Harp MD. FDA accepts biologics license application from Outlook Therapeutics for ONS-5010 for the treatment of wet AMD. Published April 9, 2025. Accessed August 28, 2025. https://www.ophthalmologytimes.com/view/fda-accepts-biologics-license-application-from-outlook-therapeutics-for-ons-5010-for-the-treatment-of-wet-amd

4. Hutton D. FDA issues CRL for Outlook Therapeutics’ ONS-5010. Published August 30, 2025. Accessed August 28, 2025. https://www.ophthalmologytimes.com/view/fda-issues-crl-for-outlook-therapeutics-ons-5010

5. Harp MD. Outlook Therapeutics stock undergoes 1-for-20 reverse stock split. Published March 14, 2024. Accessed August 28, 2025. https://www.ophthalmologytimes.com/view/outlook-therapeutics-stock-undergoes-1-for-20-reverse-stock-split