Outlook Therapeutics submits Special Protocol Assessment to FDA for ONS-5010

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Outlook Therapeutics announced that, after receiving written confirmation of the NORSE EIGHT proposed clinical trial protocol with the FDA, it has submitted a Special Protocol Assessment (SPA) request for the required additional adequate and well-controlled study of ONS-5010.

According to a news release, a Type A meeting with the FDA was held in October, and the FDA told the company it could conduct a non-inferiority study evaluating ONS-5010 versus ranibizumab in a 3-month study of treatment naïve patients with a primary efficacy endpoint at 2 months.

The company noted in its news release, it then submitted a clinical trial protocol and requested a Type A meeting with the FDA for feedback. The FDA has since provided written feedback on the protocol, which Outlook Therapeutics has incorporated. The revised protocol is the subject of the SPA request, in which Outlook Therapeutics is seeking further confirmation from the FDA that NORSE EIGHT, if successful, addresses the FDA’s requirement for a second adequate and well-controlled clinical trial to support the resubmission of the ONS-5010 BLA for wet AMD. The FDA is expected to respond to the SPA in early February 2024.

According to the company, NORSE EIGHT will be a randomized, controlled, parallel-group, masked study of neovascular age-related macular degeneration subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections. Subjects will receive injections at Day 0 (randomization), Week 4, and Week 8 visits. Approximately 400 patients are expected to be enrolled in the study.

Moreover, the company said in its news release it expects to resubmit the ONS-5010 BLA by the end of calendar year 2024 to include the results of NORSE EIGHT and the additional CMC work to address the issues identified by FDA in the Complete Response Letter issued in August 2023 to support approval.

Russell Trenary, president and CEO of Outlook Therapeutics, said the company has been working closely with FDA to meet the remaining requirements provided by the agency to support approval of ONS-5010.

“Based on our ongoing discussions with FDA, we believe we have agreement on a clinical trial protocol,’ he said in the news release. “With the SPA now submitted, we are preparing to start NORSE EIGHT in the first quarter of 2024.

“We remain dedicated in our pursuit to achieve U.S. FDA approval for the first ophthalmic formulation of bevacizumab and look forward to providing further updates,” he added.

About ONS-5010

According to the company, 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. There is no FDA-approved ophthalmic formulations of bevacizumab are available currently, and as a result clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies—products that have known risks of contamination and inconsistent potency and availability.

Should it receive FDA approval, ONS-5010 would offer an option for physicians that currently prescribe unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.

The company added that bevacizumab-vikg is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (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. Following intravitreal injection, the binding of bevacizumab-vikg to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

In August 2023, the FDA issued a complete response letter for ONS-5010.

Outlook Therapeutics recently announced the receipt of the official minutes from the Type A meeting with the FDA held last month regarding the Complete Response Letter (CRL) dated August 29, 2023, for the Biologics License Application (BLA) for ONS-5010.

Reference:

1. Outlook Therapeutics Submits Special Protocol Assessment (SPA) to FDA for Non-Inferiority Study of ONS-5010 | Outlook Therapeutics, Inc. Outlook Therapeutics, Inc. Published 2023. Accessed December 19, 2023. http://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-submits-special-protocol-assessment-spa