FDA Issues Second CRL for Outlook’s AMD Therapy

Outlook Therapeutics has received a second Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its biologics license application (BLA) for bevacizumab-vikg (ONS-5010), an investigational ophthalmic formulation of bevacizumab intended for the treatment of wet age-related macular degeneration (wet AMD).

FDA Requests Additional Efficacy Data

According to the CRL, the FDA stated it cannot approve the BLA in its current form, citing a lack of substantial evidence of effectiveness. The agency specifically noted that ONS-5010 failed to meet the primary efficacy endpoint in the NORSE EIGHT trial. While acknowledging that the NORSE TWO study met its primary endpoint, the FDA emphasized the need for confirmatory evidence to support the application.

“While we are very disappointed with this outcome, we intend to meet with the FDA to receive additional clarity on their requirements to potentially approve the first on-label bevacizumab product specifically formulated, manufactured, and packaged for intravitreal use in the United States,” said Bob Jahr, CEO, Outlook Therapeutics.

Jahr added that no other outstanding deficiencies were noted in the CRL related to the BLA submission.

Regulatory History and Prior Setbacks

This is the second CRL issued by the FDA for ONS-5010. The first, received in August 2023, cited CMC (Chemistry, Manufacturing, and Controls) issues, open observations from preapproval manufacturing inspections, and insufficient evidence of efficacy. Since then, Outlook Therapeutics has worked to address these issues and resubmitted its BLA.

Despite the FDA’s continued reservations, the product has seen progress abroad.

European and UK Regulatory Approvals

In May 2024, the European Commission granted Marketing Authorization for the product under the name Lytenava (bevacizumab gamma), making it the first and only approved ophthalmic formulation of bevacizumab for wet AMD treatment in the European Union.

Subsequently, in July 2024, the UK Medicines and Healthcare products Regulatory Agency (MHRA) also granted marketing authorization for Lytenava. As of June 2025, Lytenava became commercially available in Germany and the UK for the treatment of wet AMD.

Next Steps Following FDA Decision

Following the latest CRL, Outlook Therapeutics has stated its intent to request a meeting with the FDA to gain clarity on the requirements for potential U.S. approval. In parallel, the company will continue expanding into additional European markets and remain focused on providing a safe, on-label alternative to compounded Avastin for ophthalmic use.

“We remain committed to providing patients with a safe and effective alternative to compounded Avastin manufactured in the United States,” Jahr said.