FDA issued a Complete Response Letter for Outlook Therapeutics’ ONS-5010/LYTENAVA for wet AMD, requesting more confirmatory data. Learn what this decision means for patients, clinicians, and future approval plans.
Written By: Pharmacally Medical News Desk
Outlook Therapeutics announced that the U.S. FDA issued a Complete Response Letter (CRL) on December 31, 2025, for the company’s resubmitted Biologics License Application (BLA) for ONS-5010/LYTENAVA (bevacizumab-vikg).
This marks the third CRL for the ophthalmic bevacizumab formulation aimed at treating wet age-related macular degeneration (wet AMD). The FDA stated it cannot approve the BLA in its current form.
In the letter, the FDA acknowledged that one adequate and well-controlled study demonstrated efficacy but reiterated its request for additional confirmatory evidence. The agency did not specify what type of confirmatory data would meet expectations, leaving the development path less defined for now.
The resubmitted BLA included the full NORSE clinical trial program:
NORSE TWO: Pivotal efficacy study meeting FDA’s adequate and well-controlled criteria.
NORSE EIGHT: Non-inferiority trial vs. ranibizumab in treatment-naïve patients over 12 weeks (8-week primary endpoint), which failed to meet its primary goal a potential factor in the CRL.
Outlook Therapeutics maintains that the totality of evidence supports approval, despite the setback.
Leadership expressed disappointment but reaffirmed commitment to delivering the first FDA-approved, on-label bevacizumab for retinal specialists and patients. Currently, U.S. physicians rely on pharmacy-compounded bevacizumab, raising safety concerns due to inconsistent quality and contamination risks.
LYTENAVA (bevacizumab gamma) holds marketing authorization in the European Union and United Kingdom, available commercially in markets like Germany and the UK; the first ophthalmic bevacizumab for wet AMD there. In the U.S., ONS-5010 remains investigational.
Bevacizumab-vikg, a recombinant humanized monoclonal antibody, binds all vascular endothelial growth factor (VEGF) isoforms, blocking VEGFR-1 and VEGFR-2 on endothelial cells. This inhibits abnormal vessel growth, leakage, and retinal swelling in wet AMD a leading cause of vision loss in adults over 50, driven by fragile sub-retinal vessels.
Wet AMD is a leading cause of irreversible central vision loss in adults over 50. In this condition, abnormal, fragile blood vessels form beneath the retina, leak fluid or blood, and damage the macula. Elevated intraocular VEGF levels drive this process. Anti-VEGF injections have become the standard of care, significantly slowing disease progression for many patients.
Outlook Therapeutics is evaluating U.S. regulatory pathways while advancing global commercialization. For patients and providers, approval would standardize anti-VEGF therapy, reducing risks from off-label compounding. Outlook Therapeutics will provide further updates on any confirmatory trials or resubmission strategy as developments occur.
References
Outlook Therapeutics Provides Regulatory Update on U.S. Food and Drug Administration Review of ONS-5010/LYTENAVA™ (bevacizumab-vikg) for the Treatment of Wet AMD, 31 December 2025, https://ir.outlooktherapeutics.com/node/12456/pdf
Outlook Therapeutics Provides Regulatory Update on U.S. Food and Drug Administration Review of ONS-5010/LYTENAVA™ (bevacizumab-vikg) for the Treatment of Wet AMD, 28 August 2025, https://ir.outlooktherapeutics.com/node/12316/pdf
Outlook Therapeutics® Provides Regulatory Update on FDA Review of ONS-5010 / LYTENAVA™ (bevacizumab-vikg) for the Treatment of Wet AMD, 30 August 2023, https://ir.outlooktherapeutics.com/node/11076/pdf
A 3-month Study to Assess the Safety and Effectiveness of ONS-5010 in Subjects with Neovascular Age-related Macular Degeneration (AMD), ClinicalTrials.gov ID NCT06190093, https://clinicaltrials.gov/study/NCT06190093
Rahhal FM et al, ONS-5010 (bevacizumab-vikg) Safety and Efficacy in Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration. Ophthalmic Surg Lasers Imaging Retina. 2025 Mar;56(3):178-189. doi: 10.3928/23258160-20240924-01. Epub 2024 Nov 1. PMID: 39535413.