Outlook Therapeutics has received a setback in its efforts to bring an FDA-approved bevacizumab treatment for retinal disease to the U.S. market. The company announced that the U.S. Food and Drug Administration has issued a complete response letter (CRL) to the biologics license application (BLA) resubmission for ONS-5010/LYTENAVA (bevacizumab-vikg), stating that the application cannot be approved in its current form for the treatment of wet age-related macular degeneration (wet AMD).
According to the CRL, the FDA determined that the additional mechanistic and natural history data included in the resubmission did not change its prior assessment. While the agency acknowledged that one adequate and well-controlled clinical study demonstrated efficacy, it reiterated the need for confirmatory evidence of efficacy to support approval. The FDA did not specify what type of confirmatory evidence would be required, leaving the company with uncertainty regarding next steps.
Outlook Therapeutics emphasized that its long-term objective remains unchanged: to provide wet AMD patients and physicians with a safe, consistent, FDA-approved alternative to compounded Avastin produced in the United States. Compounded bevacizumab is widely used off-label in ophthalmology, but variability in preparation and supply has raised concerns among clinicians and regulators. Bob Jahr, Chief Executive Officer of Outlook Therapeutics, said the company was disappointed with the FDA’s decision and disagreed with the conclusion, but remains committed to pursuing U.S. approval. He reiterated the company’s belief in the clinical need and commercial potential for the first on-label bevacizumab product specifically formulated, manufactured, and packaged for intravitreal use.
The BLA resubmission for ONS-5010 was supported by the full data set from the NORSE clinical trial program. This included NORSE TWO, a pivotal, adequate, and well-controlled study that met its primary efficacy endpoint, as well as additional safety and efficacy data from other trials in the program. Among these was NORSE EIGHT, a non-inferiority study comparing ONS-5010 with ranibizumab in treatment-naïve wet AMD patients, which evaluated efficacy at eight weeks in a 12-week study period. Outlook Therapeutics maintains that the totality of evidence from NORSE TWO and the broader NORSE program should be sufficient to support approval in the United States.
While the U.S. regulatory pathway remains uncertain, Outlook Therapeutics continues to advance its international strategy. LYTENAVA has already received marketing authorization from the European Commission and the UK Medicines and Healthcare products Regulatory Agency for the treatment of wet AMD. The product became commercially available in Germany and the UK in June 2025, and the company plans to expand its presence in additional European markets. Outlook is also exploring potential partnerships to support commercialization beyond Europe.
LYTENAVA is currently the first and only authorized ophthalmic formulation of bevacizumab approved for wet AMD in the European Union and the UK, underscoring the contrast between its regulatory status abroad and the ongoing challenges in the U.S. market.