FDA accepts Outlook Therapeutics' resubmitted BLA for ONS-5010 (LYTENAVA)

The US Food and Drug Administration has accepted for review the Biologics License Application (BLA) for ONS-5010 (LYTENAVA) for the treatment of neovascular age-related macular degeneration (nAMD) from Outlook Therapeutics.¹ The resubmission is considered a Class 1 submission and has a current PDUFA target action date of July 29, 2026.

The company had submitted the BLA to the FDA at the beginning of June 2026, following a CRL the company had received in December 2025. The journey to FDA approval has been an arduous one for the company, starting in 2022 with the first BLA submission to the FDA. Since then, the company has received 3 CRLs from the organization—with many back-and-forth meetings to determine the path forward.

An appeal was cast by Outlook on the December 2025 CRL,^2,3 which was approved by the Office of New Drugs (OND) in a Formal Dispute Resolution (FDR). In the FDR, the OND determined that the results of the NORSE TWO trial (NCT03834753), together with confirmatory evidence from NORSE EIGHT natural history data, and mechanistic and pharmacodynamic data, collectively establish substantial evidence of effectiveness for bevacizumab-vikg in nAMD.

Bob Jahr, CEO of Outlook Therapeutics commented on the FDA action in a press release from the company,¹ “We are very pleased that the FDA has accepted our resubmitted BLA to review the labelling as part of the final step toward potential approval. This is great news for Outlook and the LYTENAVA team, patients and the retina community. We look forward to collaborating with the FDA over the coming weeks. We are incredibly grateful to our teams, partners, and KOLs for their resilience and dedication.”

ONS-5010/LYTENAVA is an ophthalmic formulation of bevacizumab: Bevacizumab-vikg in the US and bevacizumab gamma in the EU and UK. It is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human VEGF and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells.

If approved, LYTENAVA will be the first and only FDA-approved ophthalmic formulation of bevacizumab supported by “standardized manufacturing, FDA-approved labeling, and robust pharmacovigilance,” according to the company.

LYTENAVA currently 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.

NORSE trials

Results across the first 3 NORSE trials demonstrated a strong benefit-to-risk safety profile, with only 1 ocular inflammation adverse event across all 3 registration trials. The most common adverse reaction (≥ 5%) reported in patients receiving bevacizumab-vikg was conjunctival hemorrhage associated with the needle injection procedure (5%).^1-7

NORSE ONE was a clinical experience trial involving 61 participants with wet AMD at 9 trial sites in Australia. It compared bevacizumab-vikg to ranibizumab (Lucentis) as a treatment for wet AMD. Bevacizumab-vikg efficacy and safety data were consistent with data from historical published studies of bevacizumab in ophthalmology.^1-7

In the NORSE TWO phase 3 pivotal trial, investigators enrolled 228 patients with wet AMD at 39 sites in the US. It was designed as a superiority study comparing the safety and efficacy of bevacizumab-vikg (ophthalmic bevacizumab) dosed monthly against ranibizumab according to the regimen described in the Lucentis label. The data met both the primary and secondary end points, with high statistical significance and clinical relevance.^1-7

NORSE THREE was an open-label safety study of bevacizumab-vikg in 197 patients conducted in the US to provide the necessary number of retina patients dosed with bevacizumab-vikg 5010 to complete the safety requirements for submitting a BLA.^1-7

NORSE EIGHT was a randomized, controlled, parallel-group, masked, noninferiority study of approximately 400 patients with newly diagnosed wet AMD. Investigators randomly assigned them 1:1 to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections.^1-7

References:

1. Outlook Therapeutics Announces FDA Acceptance of Resubmitted Biologics License Application for ONS-5010/LYTENAVA™ (bevacizumab-vikg) as a Treatment for Wet AMD. Published June 16, 2026. Accessed June 17, 2026. https://www.globenewswire.com/news-release/2026/06/16/3312535/0/en/outlook-therapeutics-announces-fda-acceptance-of-resubmitted-biologics-license-application-for-ons-5010-lytenava-bevacizumab-vikg-as-a-treatment-for-wet-amd.html

2. Harp MD. Outlook Therapeutics resubmits BLA for bevacizumab-vikg (ONS-5010/LYTENAVA). Published June 1, 2026. Accessed June 17, 2026. https://www.ophthalmologytimes.com/view/outlook-therapeutics-resubmits-bla-for-bevacizumab-vikg-ons-5010-lytenava-

3. Hoffman M. FDA grants appeal for bevacizumab-vikg BLA in neovascular AMD. Published May 26, 2026. Accessed June 17, 2026. https://www.ophthalmologytimes.com/view/fda-appeal-bevacizumab-vikg-bla-neovascular-amd

4. Charters L. Stevenson S. FDA update: Outlook Therapeutics receives CRL for resubmitted ONS-5010 BLA. Published December 31, 2025. Accessed June 1, 2026. https://www.ophthalmologytimes.com/view/outlook-therapeutics-receives-crl-for-resubmitted-ons-5010-bla

5. Harp MD. FDA issues complete response letter to Outlook Therapeutics for resubmitted BLA for ONS-5010. Published August 28, 2025. Accessed June 1, 2026. https://www.ophthalmologytimes.com/view/fda-issues-complete-response-letter-to-outlook-therapeutics-for-resubmitted-bla-for-ons-5010

6. Hutton D. FDA issues CRL for Outlook Therapeutics’ ONS-5010. Ophthalmology Times. August 30, 2023. Accessed June 17, 2026. https://www.ophthalmologytimes.com/view/fda-issues-crl-for-outlook-therapeutics-ons-5010

7. Harp MD. Outlook Therapeutics' stock undergoes 1-for-20 reverse stock split. Ophthalmology Times. March 14, 2024. Accessed June 17, 2026 https://www.ophthalmologytimes.com/view/outlook-therapeutics-stock-undergoes-1-for-20-reverse-stock-split