Outlook Therapeutics, Inc. announced in a press release that the US Food and Drug Administration (FDA) has issued a complete response letter (CRL) to the ONS-5010/Lytenava (bevacizumab-vikg) biologics license application (BLA) resubmission, indicating that the FDA cannot approve the application in its present form for the treatment of wet age-related macular degeneration (wet 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 an 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 company said, 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," said Bob Jahr, chief executive officer of Outlook Therapeutics. "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."

According to Outlook Therapeutics, the ONS-5010 BLA resubmission was based on the complete data set from the NORSE clinical trial program, 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, a well-controlled noninferiority study evaluating ONS-5010 vs ranibizumab in a 12-week study of treatment-naïve patients with a primary efficacy endpoint at 8 weeks. 

Outlook Therapeutics said it 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 US.

The company also said it 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.