FDA Accepts Biologics License Application for ONS-5010 for Wet AMD

The US Food and Drug Administration (FDA) has accepted Outlook Therapeutics' resubmitted Biologics License Application (BLA) for ONS-5010 (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (AMD).1

Announced by Outlook Therapeutics on April 8, 2025, the ophthalmic form of bevacizumab is a recombinant humanized monoclonal antibody (mAb) treatment that selectively binds with high affinity to human vascular endothelial growth factor (VEGF) by binding to VEGF receptors.

The BLA has been flagged as a Class 2 review, which will involve a six-month review period from the submission date. The FDA has set a Prescription Drug User Fee Act (PDUFA) target goal date for August 27, 2025.1

“This BLA acceptance and PDUFA date are significant milestones in our continued mission to offer clinicians and their patients the first and only on-label, ophthalmic bevacizumab to treat wet AMD,” said Lawrence Kenyon, chief financial officer and interim chief executive officer of Outlook Therapeutics. “We are committed to bringing an ophthalmic bevacizumab to market in the United States and are continuing our activities for potential commercialization.”1

Resubmission of the BLA was based on the results of the 12-week NORSE EIGHT trial, originally announced in January 2025. The study was a randomized, controlled, parallel-group, masked, non-inferiority study, including newly diagnosed wet AMD subjects. Participants were randomized in a 1:1 ratio and were given either 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections at day 0, week 4, and week 8.2

NORSE EIGHT’s primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 8 compared to ranibizumab. Although it did not achieve this endpoint at week 8, by month 3 it reached the prespecified noninferiority margin with a difference in mean BCVA of -1.009 letters (95% CI, -2.865 to 0.848, P =.0043) between the two treatments. Additionally, ONS-5010 treatments were well tolerated overall, with ocular adverse event rates comparable to ranibizumab.2

In 2023, the company held Type A meetings with the FDA to address the Complete Response Letter (CRL) received earlier that year. The FDA established in those meetings the 8-week primary efficacy endpoint that NORSE EIGHT failed to meet.1

Outlook Therapeutics announced their belief the 12-week results, combined with data from previous NORSE clinical trials and the chemistry, manufacturing and controls (CMC) information that the FDA had requested, are grounds to approve ONS-5010 in the United States.1

Notably, ONS-5010 has already achieved regulatory approval in the European Union and the United Kingdom, becoming the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet AMD.1

If approved by the FDA, the drug will be branded LYTENAVA and will likely receive 12 years of regulatory exclusivity.

References

1. Outlook Therapeutics Inc. Outlook Therapeutics Announces Acceptance of Biologics License Application by U.S. FDA for ONS-5010 as a Treatment for Wet AMD. Outlook Therapeutics Inc. April 8, 2025. Accessed April 9, 2025. https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-announces-acceptance-biologics-license-0

2. Outlook Therapeutics Inc. Outlook Therapeutics Announces Presentation of Efficacy and Safety Results from NORSE EIGHT Clinical Trial Evaluating ONS-5010 for the Treatment of Wet AMD. Outlook Therapeutics Inc. January 23, 2025. Accessed April 9, 2025. https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-announces-presentation-efficacy-and-safety