The road to U.S. approval for ONS-5010 has been anything but smooth.
Outlook Therapeutics (New Jersey, USA) is once again turning to the U.S. Food and Drug Administration (FDA) after facing another regulatory setback for its wet AMD candidate, ONS-5010 (Lytenava, bevacizumab-vikg). Following a second complete response letter (CRL), the company has formally requested a Type A Meeting to clarify what confirmatory efficacy evidence regulators will require to advance its resubmitted biologics license application (BLA).
A road marked by challenges
The most recent CRL, issued on August 27, 2025, stemmed from the NORSE EIGHT trial, which did not meet its primary efficacy endpoint.1 While the FDA acknowledged the earlier Phase III NORSE TWO pivotal trial had demonstrated safety and efficacy, the agency concluded that additional confirmatory evidence is necessary to support approval.2
This marks the second CRL for ONS-5010. The FDA first rejected the therapy in August 2023, citing chemistry, manufacturing and controls (CMC) issues, unresolved findings from pre-approval inspections, and what it called a lack of substantial evidence. That rejection prompted Outlook’s first Type A Meeting in September 2023.3
READ MORE: Outlook Therapeutics’ Bevacizumab Formulation Fails Primary Endpoint in nAMD Trial
Despite the challenges, Outlook leaders remain committed to the program.
“We believe this Type A meeting will provide us with additional clarity on the FDA’s requirements to remedy the deficiency identified in the CRL,” said Bob Jahr, CEO of Outlook Therapeutics, in a news release. “Our mission has not changed: to deliver a safe and effective FDA-approved alternative to compounded bevacizumab, which U.S. patients and physicians have relied on off-label for years despite concerns over potency, sterility, consistency and regulatory oversight.”
If approved by the FDA, ONS-5010 would be the first and only on-label ophthalmic bevacizumab for thousands of patients needing anti-VEGF treatments for wet AMD.
READ MORE: NexThera, Oculis and Bayer Report Advances in Retinal Disease Therapies
How ONS-5010 works
ONS-5010 is a purpose-designed ophthalmic formulation of bevacizumab. Unlike compounded bevacizumab, which is adapted from oncology use, ONS-5010 is built specifically for intravitreal injection to treat retinal diseases.
Its active component, bevacizumab-vikg, is a recombinant humanized monoclonal antibody (mAb). It binds with high affinity to all isoforms of vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biological activity by blocking its interaction with the receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on endothelial cells.
By cutting off VEGF signaling, ONS-5010 reduces endothelial cell proliferation, vascular leakage and abnormal new blood vessel formation—the key drivers of wet AMD.
Momentum in Europe
While Outlook struggles with U.S. regulators, the therapy has made steady gains abroad. In March 2024, the European Medicines Agency (EMA) issued a positive CHMP opinion for ONS-5010.
By June 2025, the drug became commercially available in Germany and the UK for wet AMD, pending additional national reimbursement approvals across the EU.
READ MORE: Intravitreal Bevacizumab Receives EU Approval for Wet AMD Treatment
The path forward
The upcoming second Type A Meeting will be pivotal in determining ONS-5010’s U.S. future. If Outlook can reach alignment with the FDA on the confirmatory trial requirements, it may yet move the therapy back toward approval.
Until then, the company stands at a crossroads: with international momentum building but U.S. approval still uncertain, all eyes are on whether ONS-5010 can overcome its latest regulatory hurdle and finally deliver a long-awaited alternative to compounded bevacizumab for American patients.
Editor’s Note: Official press release by Outlook Therapeutics can be found here. This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore.
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. Outlook Therapeutics. August 28, 2025. Available at: https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeutics-provides-regulatory-update-us-food-and-drug. Accessed on September 4, 2025.
- Outlook Therapeutics Presents NORSE TWO Phase 3 Pivotal Safety and Efficacy Data for ONS-5010 / LYTENAVA™ (bevacizumab-vikg) at the Retina Subspecialty Day, American Academy of Ophthalmology (AAO) 2021 Annual Conference. Outlook Therapeutics. November 13, 2021. Available at: https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeutics-presents-norse-two-phase-3-pivotal-safety. Accessed on September 4, 2025.
- Outlook Therapeutics® Requests Type A Meeting With FDA. Outlook Therapeutics. September 29, 2023. Available at: https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-requests-type-meeting-fda. Accessed on September 4, 2025.