Outlook Therapeutics announced in a press release that the US Food and Drug Administration (FDA) has issued a complete response letter (CRL) to its biologics license application resubmission for ONS-5010, the company's investigational ophthalmic formulation of bevacizumab for neovascular (“wet”) age-related macular degeneration (nAMD). The FDA indicated in the CRL that it cannot approve the application in its present form.

According to the company, 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 although an adequate and well-controlled study demonstrated efficacy, additional confirmatory evidence of efficacy must be submitted to support the application. However, the company said, the FDA has not indicated what type of confirmatory evidence would be acceptable.

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  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. 

Bevacizumab (Avastin; Genentech) was originally approved for cancer treatment in 2004. It has been used off-label since around 2005 to treat nAMD, following early clinical evidence and physician reports suggesting its effectiveness in reducing retinal fluid and improving vision. ONS-5010 is designed as an on-label alternative to compounded bevacizumab. If approved, the product will be marketed in the United States as Lytenava (bevacizumab-vikg). ONS-5010 has already received marketing authorization in the European Union and the United Kingdom, with commercial sales beginning in Germany and the UK in June 2025. RP