Core Viewpoint - Outlook Therapeutics' stock experienced a significant decline following the FDA's issuance of a complete response letter (CRL) regarding its biologics license application (BLA) for ONS-5010, a treatment for wet age-related macular degeneration (wet AMD) [1][2][9] FDA Update - The FDA's CRL indicated that the application could not be approved in its current form due to a lack of substantial evidence of effectiveness [2][8] - The FDA noted that ONS-5010 did not meet the primary efficacy endpoint in the NORSE EIGHT trial, necessitating additional confirmatory evidence to support the application [3][8] Next Steps for the Company - The CEO of Outlook Therapeutics expressed disappointment but stated intentions to meet with the FDA for further clarification on approval requirements for ONS-5010 [5] - The company plans to continue expanding into European markets, having already received approval for Lytenava (bevacizumab gamma) for wet AMD in the EU and the U.K. [6][7] Clinical Trial Insights - The FDA acknowledged that the NORSE TWO trial met its safety and efficacy endpoints, but cited several issues including CMC concerns and open observations from pre-approval inspections as reasons for not approving the application [4][8] - The FDA has indicated that a second adequate and well-controlled clinical trial is required, suggesting a non-inferiority study comparing ONS-5010 to ranibizumab [9]