FDA grants appeal for bevacizumab-vikg BLA in neovascular AMD

According to a new announcement, the FDA has granted Outlook Therapeutics' appeal following the completion of the Formal Dispute Resolution (FDR) process with the Office of New Drugs (OND), concluding substantial evidence of effectiveness has been established for bevacizumab-vikg (Lytenava; Outlook Therapeutics) for the treatment of neovascular age-related macular degeneration (nAMD). Outlook Therapeutics plans to resubmit the bevacizumab-vikg biologics license application (BLA) to the FDA in June 2026.

The FDR decision reverses the trajectory set by a Complete Response Letter (CRL) issued on December 30, 2025, and establishes a clear regulatory path toward potential US approval for the first ophthalmic formulation of bevacizumab, supported by an FDA-approved manufacturing process and labeling. Lytenava, also known as ONS-5010, already holds marketing authorization from the European Commission and the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) for wet AMD, with commercial launches underway in Germany, Austria, and the United Kingdom.

"We appreciate the opportunity to engage with the FDA through the FDR process,” Bob Jahr, chief executive officer of Outlook Therapeutics, said in a statement. "The agency’s action on our appeal provides a clear path forward toward US approval."

In its formal response, OND determined that the results of the NORSE TWO trial (NCT03834753), together with confirmatory evidence from NORSE EIGHT (NCT06190093), natural history data, and mechanistic and pharmacodynamic data, collectively establish substantial evidence of effectiveness for bevacizumab-vikg in nAMD. The decision directs the Division of Ophthalmology and the Office of Specialty Medicine to work with Outlook Therapeutics to reach an agreement on final labeling.

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Per the formal decision, the resubmission is anticipated to proceed as a Class 1 resubmission, with a PDUFA date and decision expected within 60 days of FDA receipt. The company had initiated the FDR process after a Type A meeting with the Division of Ophthalmology and Office of Specialty Medicine following the December 2025 CRL. The FDR pathway allows applicants to escalate unresolved scientific or regulatory disputes to senior FDA leadership for a binding determination.

Bevacizumab-vikg regulatory history and path to FDA approval

Bevacizumab-vikg is a recombinant humanized monoclonal antibody binding to all isoforms of human vascular endothelial growth factor (VEGF), neutralizing VEGF's biologic activity through steric blockade of VEGF binding to its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR) on endothelial cell surfaces. Following intravitreal injection, blockade of VEGF-receptor interaction reduces endothelial cell proliferation, vascular leakage, and neovascularization in the retina. The agent is produced in the United States and, if approved, would carry FDA-approved labeling and pharmacovigilance infrastructure, differentiating it from compounded bevacizumab preparations currently used off-label in retinal practice.

Compounded bevacizumab has long been used as a lower-cost alternative to approved anti-VEGF agents in nAMD, but without FDA oversight of the manufacturing process, product consistency, or labeling. An approved ophthalmic bevacizumab formulation would offer a regulated option within the anti-VEGF class, potentially expanding the formulary landscape for retina practices and payers navigating cost-versus-access considerations. The Class 1 designation for the resubmission indicates that the response fully addresses the issues, supporting the 60-day review clock.

Outlook Therapeutics has received 3 CRLs from the FDA for its ONS-5010/Lytenava application for wet AMD. The timeline of the CRLs is as follows:

• First CRL: Issued in August 2023. This was due to Chemistry, Manufacturing, and Controls (CMC) issues, open observations from manufacturing inspections, and a lack of substantial evidence, according to the company.²
• Second CRL: Issued in August 2025. This letter cited a lack of substantial evidence of effectiveness and recommended more confirmatory efficacy data, according to the company.^2,3
• Third CRL: Issued on December 31, 2025, for the subsequent Biologics License Application (BLA) resubmission. The FDA stated that the additional data provided did not alter its previous conclusion that confirmatory evidence of efficacy is needed.⁴

If the BLA resubmission proceeds as planned in June 2026 and receives a 60-day review, an FDA decision on bevacizumab-vikg would be expected in August 2026, positioning it as a new entrant into the approved anti-VEGF landscape alongside ranibizumab, aflibercept, faricimab, and brolucizumab.

REFERENCES

1. Outlook Therapeutics, Inc. Outlook Therapeutics Wins Appeal Following Formal Dispute Resolution Process for ONS-5010/LYTENAVA (bevacizumab-vikg). Published May 26, 2026. Accessed May 26, 2026. https://www.globenewswire.com/news-release/2026/05/26/3300933/0/en/outlook-therapeutics-wins-appeal-following-formal-dispute-resolution-process-for-ons-5010-lytenava-bevacizumab-vikg.html

2. Hutton D. FDA issues CRL for Outlook Therapeutics’ ONS-5010. Ophthalmology Times. August 30, 2023. Accessed November 13, 2025. https://www.ophthalmologytimes.com/view/fda-issues-crl-for-outlook-therapeutics-ons-5010

3. Outlook Therapeutics requests Type A meeting with FDA following second CRL for ONS-5010. Ophthalmology Times. September 3, 2025. Accessed November 13, 2025. https://www.ophthalmologytimes.com/view/outlook-therapeutics-requests-type-a-meeting-with-fda-following-second-crl-for-ons-5010

4. Harp MD. FDA issues complete response letter to Outlook Therapeutics for resubmitted BLA for ONS-5010. Ophthalmology Times. August 28, 2025. Accessed November 13, 2025. https://www.ophthalmologytimes.com/view/fda-issues-complete-response-letter-to-outlook-therapeutics-for-resubmitted-bla-for-ons-5010