Ophthalmic Bevacizumab Faces Revised Regulatory Path After Type A Meeting

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Outlook Therapeutics has announced the receipt of the official minutes from a Type A meeting with the US Food and Drug Administration (FDA) regarding the Complete Response Letter (CRL) issued for the Biologics License Application (BLA) for ONS-5010, or bevacizumab-vikg (LYTENAVA), for the treatment of wet age-related macular degeneration (AMD).¹

Announced on November 27, 2023, per the FDA, the company is required to complete an additional adequate and well-controlled study to support the BLA for ONS-5010. Outlook Therapeutics has been informed it can conduct a 3-month non-inferiority study assessing ONS-5010 versus ranibizumab among treatment-naive patients with wet AMD, with a primary efficacy endpoint at 60 days.

Citing recommendations by the agency at the Type A Meeting, Outlook Therapeutics has worked with the division of ophthalmology to design an appropriate study to match FDA requirements. Both parties have identified necessary approaches to resolve Chemistry Manufacturing and Controls issues cited in the CRL dated August 29, 2023.

“We are encouraged by the productive discussions we have had with the FDA regarding the next steps for our ONS-5010 approval pathway,” said Russell Trenary, the president and chief executive officer of Outlook Therapeutics, in a statement.¹ “We continue to believe in the potential of ONS-5010 to address the need here in the US, as well as globally, for an approved ophthalmic bevacizumab that meets FDA standards for the treatment of wet AMD.”

Based on the Type A meeting and other discussions with the FDA, Outlook Therapeutics has submitted a protocol for review in December at a Type A meeting with the FDA. Pending confirmation of the protocol details from the agency, Outlook Therapeutics plans to submit a Special Protocol Assessment to confirm if successful, the trial, combined with efforts related to the identified manufacturing issues, would support approval of the resubmitted ONS-5010 BLA.

The BLA submission was based on the NORSE clinical program consisting of NORSE ONE, NORSE TWO, and NORSE THREE.² The pivotal phase 3 NORSE TWO clinical trial assessed the efficacy and safety of ONS-5010 against ranibizumab, showing 41.7% of patients receiving ONS-5010 gained ≥15 letters and had a mean visual acuity increase of 11.2 letters (P = .0043).

Outlook Therapeutics noted its expectation for the resubmission of the ONS-5010 by the end of the calendar year in 2024, pending final agreement on the proposed clinical trial protocol with the FDA and successful completion of the trial.¹

References

1. _{Outlook Therapeutics, Inc. Outlook therapeutics® announces receipt of type A meeting minutes and reiterates regulatory path forward for ONS-5010. GlobeNewswire News Room. November 27, 2023. Accessed November 27, 2023. https://www.globenewswire.com/news-release/2023/11/27/2786142/0/en/Outlook-Therapeutics-Announces-Receipt-of-Type-A-Meeting-Minutes-and-Reiterates-Regulatory-Path-Forward-for-ONS-5010.html.}
2. _{Campbell P. FDA issues CRL for ophthalmic bevacizumab in wet AMD. HCP Live. August 31, 2023. Accessed November 27, 2023. https://www.hcplive.com/view/fda-issues-crl-for-ophthalmic-bevacizumab-in-wet-amd.}