The FDA issued its third Complete Response Letter (CRL) on December 31, 2025, for Outlook Therapeutics' resubmitted BLA of ONS-5010 (bevacizumab-vikg/Lytenava) for wet AMD, stating additional data did not provide sufficient confirmatory efficacy evidence despite NORSE TWO showing efficacy.125
KOL David A. Eichenbaum, MD, indicated US approval is unlikely due to issues like NORSE EIGHT failing noninferiority vs. ranibizumab, suggesting a need for another well-designed trial.2
ONS-5010/Lytenava is already approved in the EU and UK, with Outlook exploring further expansion outside the US as a key opportunity amid US setbacks.1245
The resubmission included full NORSE trial data (NORSE ONE, TWO, THREE, EIGHT), but FDA requires more confirmatory evidence.134
Outlook Therapeutics plans to pursue all US pathways while advancing commercial strategy internationally.15
Sources:
1. https://ophthalmologymanagement.com/news/2026/fda-issues-crl-for-outlooks-resubmitted-ons5010-bla
2. https://www.ophthalmologytimes.com/view/outlook-therapeutics-receives-crl-for-resubmitted-ons-5010-bla
3. https://www.pharmaceutical-technology.com/news/outlook-therapeutics-fda-response/
4. https://glance.eyesoneyecare.com/stories/2026-01-06/fda-rejects-outlook-therapeutics-third-bla-submission-of-bevacizumab-for-wet-amd/
5. https://eyewire.news/news/fda-issues-another-crl-to-outlook-therapeutics-for-wet-amd-drug-candidate-lytenava