FDA Once Again Turns Down Outlook Therapeutics' Wet AMD Candidate

The FDA issued a complete response letter (CRL) to Outlook Therapeutics for its biologics license application (BLA) resubmission for bevacizumab-vikg, an investigational ophthalmic formulation of bevacizumab for the treatment of wet AMD. 

In the CRL, the FDA said it could not approve the application in its present form, citing a lack of substantial evidence of effectiveness. 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. The FDA reiterated that NORSE TWO met its primary endpoint for effectiveness.

“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. We remain committed to providing patients with a safe and effective alternative to compounded Avastin manufactured in the United States,” said Bob Jahr, Chief Executive Officer of Outlook Therapeutics. “It is important to also note that the CRL identified no other outstanding deficiencies in our BLA.”

In August 2023, the FDA has issued its first CRL to the company’s BLA for ONS-5010, citing at the time 'several CMC issues, open observations from preapproval manufacturing inspections, and a lack of substantial evidence.' However, in May 2024, Outlook received European Commission Marketing Authorization for the drug, which is branded as Lytenava (bevacizumab gamma). Lytenava became the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in the EU. Two months later, the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization for Lytenava. In June 2025, Lytenava became commercially available in Germany and the UK for the treatment of wet AMD. 

In addition to requesting a meeting with the FDA to explore pathways for potential approval in the US, Outlook said it intends to continue its efforts to expand into additional markets in Europe.