Outlook Therapeutics, Inc. – FDA CRL

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Outlook Therapeutics, Inc. for its Biologics License Application (BLA) 761320 for bevacizumab-vikg injection. Dated August 27, 2025, the letter states that the application cannot be approved in its current form due to a lack of substantial evidence of the product's effectiveness.

The primary issue identified is that while one study, NORSE 2, met its primary endpoint, a critical study, NORSE EIGHT, failed to meet its primary efficacy endpoint, which was to demonstrate non-inferiority to ranibizumab for the treatment of wet-AMD. Consequently, the FDA requires Outlook Therapeutics to submit additional confirmatory evidence of efficacy to support the application.

Further actions required include addressing proposed prescribing information, carton, and container labeling once the efficacy concerns are resolved. The company must also resubmit the proposed proprietary name, LYTENAV, after all identified deficiencies are addressed. A comprehensive safety update is mandated, encompassing detailed changes in the safety profile, presentation of new and combined safety data from all studies, updated exposure information, and a summary of worldwide safety experience.

Outlook Therapeutics has one year to resubmit a complete response addressing all deficiencies. The resubmission must be clearly marked as such, as partial responses will not initiate a new review cycle. The product cannot be legally marketed until it receives FDA approval, and the company may request a meeting to discuss the necessary steps for resubmission and approval.