Outlook Therapeutics Resubmits BLA for ONS-5010 as a Treatment for Wet AMD

Outlook Therapeutics, Inc. (OTLK) has resubmitted its Biologics License Application (BLA) for ONS-5010, an ophthalmic formulation of bevacizumab, to the U.S. Food and Drug Administration (FDA) as a treatment for wet age-related macular degeneration (wet AMD). The resubmission follows the FDA's Complete Response Letter (CRL) in August 2023, which highlighted several Chemistry, Manufacturing, and Controls (CMC) issues and open observations from pre-approval manufacturing inspections. The company has addressed these concerns and provided additional CMC information in its resubmission.

The NORSE EIGHT clinical trial, a 12-week non-inferiority study comparing ONS-5010 to ranibizumab, was conducted to provide the necessary evidence to support approval of the ONS-5010 BLA in the United States. The trial enrolled 400 newly diagnosed wet AMD subjects, who were randomized in a 1:1 ratio to receive either 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections at Day 0, Week 4, and Week 8 visits, with a final study visit at Week 12. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to Week 8.

The results of the NORSE EIGHT trial showed that ONS-5010 demonstrated a mean BCVA improvement of +3.3, +4.2, and +5.5 letters at months one, two, and three, respectively. While the trial did not meet the pre-specified non-inferiority endpoint at Week 8, it did meet the non-inferiority margin at Month 3 (P=0.0043), applying statistical parameters from the Week 8 primary endpoint. This suggests that ONS-5010 has the potential to provide early and sustained anatomical improvements comparable to ranibizumab. The safety profile of ONS-5010 remained consistent with previous NORSE trials (NORSE ONE, NORSE TWO, and NORSE THREE), with no cases of retinal vasculitis reported in either study arm. The most common adverse event was conjunctival hemorrhage, occurring in 5 participants (2.5%) in both groups.

Outlook Therapeutics has also secured funding for clinical trials and commercial launch, entering into securities purchase agreements with certain institutional and accredited investors for a private placement of up to $172 million. This funding is expected to be sufficient to take ONS-5010 through potential FDA approval and fund commercial launch.

The company remains committed to bringing an ophthalmic bevacizumab to market in the United States and providing retina patients suffering from wet AMD with a much-needed treatment option that has the potential to address the problems associated with unapproved repackaged bevacizumab. The resubmission of the ONS-5010 BLA marks a significant milestone and puts the company another step closer to a transformed Outlook Therapeutics.