The FDA Does Not Approve Outlook Therapeutics' BLA for Lytenava for the Treatment of Wet AMD

Outlook Therapeutics announced the FDA has issued a complete response letter (CRL) to the company’s BLA for ONS-5010 (Lytenava), an investigational ophthalmic formulation of bevacizumab under development to treat wet AMD. While the FDA acknowledged the NORSE TWO pivotal trial met its safety and efficacy endpoints, Outlook stated that the FDA could not approve the Biologics License Application (BLA) during this review cycle due to 'several CMC issues, open observations from preapproval manufacturing inspections, and a lack of substantial evidence.'

“We continue to believe in the public health need to provide the retina community with an FDA-approved bevacizumab treatment option for wet AMD. We will request a formal meeting as soon as possible with the FDA to further understand the BLA deficiencies and how best to resolve them. Following this meeting with the FDA, the company will be able to discuss next steps and the expected timing for resolution,” Russell Trenary, President and CEO of Outlook Therapeutics, said in a company news release.

In a conference call with investors Wednesday morning, Mr. Trenary said the company will be requesting a Type A meeiting with the FDA to further discuss the issues raised in the CRL and what is needed for a resolution.  

“We are reviewing carefully the CRL that came in. We will be requesting a Type A meeting once we have produced the briefing documents we think we be appropriate for that. We do have, retained at Outlook, a number of former FDA reviewers and former FDA attorneys to help us ensure that we understand what all the questions are and have a chance to vet all of the answers we are producing," Mr. Trenary said. "I think we have an outstanding technical team who will be able to address all of the CMC issues and we would anticipate that once we get on the other side of the Type A meeting, we’ll be in a better position to outline what the path is forward.”

The CRL is the second setback for Outlook. In May 2022, the company voluntarily withdrew its BLA for ONS-5010 after the agency requested additional information in order to complete the BLA filing. The application was resubmitted in August 2022 after the company said it provided the additional information required by the FDA. 

ONS-5010 is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. If approved, ONS-5010 would provide an FDA-approved option for physicians that currently prescribe unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.