Outlook Therapeutics announced that the US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to the ONS-5010/LYTENAVA (bevacizumab-vikg) Biologics Licence Application (BLA) resubmission, indicating that the FDA cannot approve the application in its present form for the treatment of wet Age-related Macular Degeneration (AMD).

In the CRL, the FDA noted that the additional mechanistic and natural history data information provided in the BLA resubmission does not alter the previous review conclusion that while the one adequate and well-controlled study demonstrated efficacy, the FDA has again recommended that confirmatory evidence of efficacy be submitted to support the application, however the FDA has not indicated what type of confirmatory evidence would be acceptable.

“Our goal has always been to provide wet AMD patients and their physicians with a safe, consistent, FDA-approved alternative to compounded Avastin manufactured in the United States, and that goal has not changed. We are disappointed and disagree with this decision, but we remain fully committed to taking all necessary steps to receive approval in the United States. We continue to believe strongly in the clinical need and commercial potential of the first on-label bevacizumab product for patients in the United States that is specifically formulated, manufactured and packaged for intravitreal use,” commented Bob Jahr, Chief Executive Officer, Outlook Therapeutics.

The ONS-5010 BLA resubmission was based on the complete data set from the NORSE clinical trial programme, which included the successful NORSE TWO adequate and well-controlled pivotal clinical trial as well as confirmatory safety and efficacy data from all other NORSE trials, including NORSE EIGHT, an adequate and well-controlled non-inferiority study evaluating ONS-5010 versus ranibizumab in a 12-week study of treatment naïve patients with a primary efficacy endpoint at 8 weeks.

Outlook Therapeutics continues to believe that the complete data set for NORSE TWO, combined with the data from the other NORSE clinical trials, provides the required evidence to support approval of the ONS-5010 BLA in the United States.

Outlook Therapeutics is currently exploring all available pathways for potential approval in the US and intends to continue its efforts to expand into additional markets in Europe and other regions. As previously announced, LYTENAV (bevacizumab gamma) was granted Marketing Authorisation by the European Commission in the EU and Marketing Authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of wet AMD.

In June 2025, LYTENAVA (bevacizumab gamma) became commercially available in Germany and the UK for the treatment of wet AMD. In addition to current plans to expand its commercial presence in select countries in Europe, Outlook Therapeutics continues to speak with and explore collaborations with potential commercial and distribution partners in additional European countries, as well as outside of Europe. LYTENAVA (bevacizumab gamma) is the first and only authorised ophthalmic formulation of bevacizumab for use in treating wet AMD in adults in the European Union and UK.