Outlook Therapeutics Submits ONS-5010 Special Protocol Assessment to FDA

Credit: US Food and Drug Administration

Outlook Therapeutics has submitted a Special Protocol Assessment (SPA) request to the US Food and Drug Administration (FDA) for a required additional adequate and well-controlled study of ONS-5010, an ophthalmic formulation of bevacizumab indicated for the treatment of neovascular age-related macular degeneration (nAMD) and other retinal diseases.¹

Announced on December 19, 2023, the submission followed the receipt of written confirmation of the NORSE EIGHT proposed clinical trial protocol from the FDA. Prior communication between the two parties occurred in a Type A meeting held in October 2023.²

The FDA is expected to submit a response to the SPA in early February 2024 and Outlook Therapeutics expects resubmission of the ONS-5010 Biologics License Application (BLA) by the end of calendar year 2024.¹

“We have been working closely with the FDA to meet the remaining requirements provided by the Agency to support approval of ONS-5010. Based on our ongoing discussions with the FDA, we believe we have agreement on a clinical trial protocol,” Russel Trenary, president and chief executive officer of Outlook Therapeutics, said in a statement.¹

At the Type A meeting in October, Outlook Therapeutics was informed it could conduct a non-inferiority study evaluating ranibizumab in a 3-month study of treatment-naive patients with a primary efficacy endpoint at 2 months.² As recommended by the Agency, the company submitted a clinical trial protocol and requested a Type A meeting with the FDA to receive feedback on the trial design.

The revised protocol is now the basis of the SPA request, in which the company is seeking confirmation from the Agency that the successful outcome of NORSE EIGHT will address the FDA’s requirement for a second adequate and well-controlled trial to support the resubmitting of the ONS-5010 biologics license application (BLA) for wet AMD.¹

According to the company, the NORSE EIGHT trial will be a randomized, controlled, parallel-group, masked study of nAMD subjects randomized in a 1:1 ratio to receive intravitreal injections of 1.25 mg ONS-5010 or 0.5 mg ranibizumab. Participants will receive injections at Day 0, Week 4, and Week 8 visits. The company expects approximately 400 to be enrolled in the trial and the trial is planned to begin in the first quarter of 2024.

Previously, in August 2023, ONS-5010 received a Complete Response Letter (CRL), with the FDA citing several Chemistry Manufacturing and Controls (CMC) issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence as reasons for missed approval.³

Outlook Therapeutics now expects to resubmit the ONS-5010 BLA by the end of 2024, to include the results of the NORSE EIGHT trial and additional CMC work to address issues identified by the FDA in the CRL.¹

ONS-5010 is an investigational ophthalmic formulation of bevacizumab under development for the treatment of retinal diseases, as no FDA-approved ophthalmic bevacizumab is currently available. Clinicians wanting to treat patients with retinal diseases with bevacizumab need to use unapproved repackaged IV bevacizumab provided by compounding formulations, which have been linked to risks of contamination and inconsistent potency and availability.

“With the SPA now submitted, we are preparing to start NORSE EIGHT in the first quarter of 2024,” Trenary said. “We remain dedicated in our pursuit to achieve US FDA approval for the first ophthalmic formulation of bevacizumab and look forward to providing further updates.”

References

1. _{Outlook therapeutics® submits Special protocol assessment (SPA) to FDA for non-inferiority study of ONS-5010. Outlook Therapeutics, Inc. December 19, 2023. Accessed December 21, 2023. https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-submits-special-protocol-assessment-spa.}
2. _{Iapoce C. Ophthalmic bevacizumab faces revised regulatory path after type A meeting. HCP Live. November 27, 2023. Accessed December 21, 2023. https://www.hcplive.com/view/ophthalmic-bevacizumab-revised-regulatory-path-type-a-meeting.}
3. _{Campbell P. FDA issues CRL for ophthalmic bevacizumab in wet AMD. HCP Live. August 31, 2023. Accessed December 21, 2023. https://www.hcplive.com/view/fda-issues-crl-for-ophthalmic-bevacizumab-in-wet-amd.}