The FDA asks for more proof, pushing Outlook’s ophthalmic bevacizumab ambitions back into review mode.
Another lap around the regulatory track has ended without a checkered flag for Outlook Therapeutics (New Jersey, USA). The company has hit a fresh U.S. Food and Drug Administration (FDA) hurdle in its long-running effort to bring an approved ophthalmic bevacizumab to market for wet age-related macular degeneration (AMD).
Outlook Therapeutics has disclosed that the FDA issued a Complete Response Letter (CRL) for the resubmitted biologics license application for ONS-5010 (Lytenava, bevacizumab-vikg), stating that the application cannot be approved in its current form. According to the company, the FDA again cited the need for additional confirmatory evidence of efficacy, without detailing the specific type or scope of data required to address the agency’s concerns.
ONS-5010 is an ophthalmic-specific formulation of bevacizumab intended for intravitreal use in patients with wet AMD. Although bevacizumab has been a mainstay of off-label retinal therapy for years, Outlook’s program is focused on delivering a formulation developed and manufactured specifically for ophthalmic use, with the aim of securing FDA approval for this indication.
READ MORE: All Eyes on Geographic Atrophy at APVRS 2025
Regulatory history and prior submissions
The resubmitted BLA included data from the company’s NORSE clinical trial program, incorporating late-stage studies designed to demonstrate safety and efficacy in wet AMD. Outlook has previously stated that these trials achieved clinically meaningful outcomes and met their primary endpoints. Despite this, the FDA has maintained that the evidence submitted to date does not satisfy its approval standards.
In its latest communication, the agency did not raise new safety concerns and did not identify deficiencies related to manufacturing, chemistry or controls. Instead, the FDA’s feedback remained centered on the robustness and confirmation of efficacy data, a consistent theme throughout its review of the program.
The absence of detailed guidance on what additional evidence would be sufficient complicates next steps for Outlook. Without clearer regulatory direction, the company must now consider whether further clinical studies are warranted or whether alternative regulatory approaches may be viable.
READ MORE: FDA Approves EYLEA HD for RVO and Monthly Dosing Across Indications
Company response and next steps
Outlook said it is evaluating all available options in response to the CRL and reaffirmed its commitment to advancing ONS-5010 toward potential U.S. approval. The company emphasized plans to engage further with the FDA to better understand the agency’s expectations and determine an appropriate path forward.
“Our goal has always been to provide wet AMD patients and their physicians with a safe, consistent, FDA-approved alternative to compounded Avastin [Genentech, California, USA] manufactured in the United States, and that goal has not changed,” commented Bob Jahr, chief executive officer at Outlook, in a news release. “We are disappointed and disagree with this decision, but we remain fully committed to taking all necessary steps to receive approval in the United States. We continue to believe strongly in the clinical need and commercial potential of the first on-label bevacizumab product for patients in the United States that is specifically formulated, manufactured and packaged for intravitreal use.”
While the CRL delays any near-term approval timeline, the company reiterated its confidence in the therapeutic potential of its ophthalmic bevacizumab formulation. Outlook also noted that ONS-5010 has already received regulatory authorization in certain international markets, where it is currently being commercialized under local approvals.
READ MORE: MacuMira and Keeler Join Forces to Advance Non-Invasive Dry AMD Treatment Worldwide
The takeaway
The FDA’s latest Complete Response Letter highlights the ongoing regulatory complexity of converting a widely used off-label therapy into an FDA-approved ophthalmic product for wet AMD.
Although safety and manufacturing issues were not part of the agency’s concerns, the continued emphasis on confirmatory efficacy data underscores the high evidentiary bar for U.S. approval.
For Outlook Therapeutics, the decision extends the regulatory runway and sharpens the focus on defining a clearer path forward with the FDA, as the company weighs whether additional clinical evidence will be required before ONS-5010 can move closer to the finish line.
Editor’s Note: 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.