Outlook Therapeutics Presents Results from NORSE EIGHT Trial Evaluating ONS-5010 for the Treatment of Wet AMD

Outlook Therapeutics announced the presentation of data from NORSE EIGHT at the Hawaiian Eye and Retina 2025 Meeting.

Baruch D. Kuppermann, MD, PhD, of Gavin Herbert Eye Institute, University of California, Irvine, CA presented the abstract titled, “ONS-5010 (bevacizumab-vikg) versus Ranibizumab for Neovascular Age-related Macular Degeneration: Results from the NORSE-EIGHT Noninferiority Randomized Trial,” highlighting the company’s 12-week safety and efficacy results for the NORSE EIGHT clinical trial evaluating ONS-5010 in wet AMD patients.

The NORSE EIGHT clinical trial was a randomized, controlled, parallel-group, masked, noninferiority study of newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at day 0 (randomization), week 4, and week 8 visits, and returned for a final study visit at week 12. The primary endpoint was mean change in BCVA from baseline to week 8.

Key Highlights

• Mean BCVA at baseline was 58.8 ETDRS letters for the ONS-5010 group and 59.9 letters for the ranibizumab group
• ONS-5010 demonstrated mean BCVA improvements of +3.3, +4.2 and +5.5 letters at Months 1, 2, and 3 respectively
• The difference in mean BCVA between ONS-5010 and ranibizumab was -1.009 letters (95% confidence interval, -2.865, 0.848), meeting the noninferiority margin at Month 3 (P=0.0043) (applying the statistical parameters from the week 8 primary endpoint with the lower bound of the non-inferiority margin at -3.5 with a 95% confidence interval)
• As previously announced, in the NORSE EIGHT trial, ONS-5010 did not meet the prespecified non-inferiority endpoint at week 8 set forth in the special protocol assessment with the FDA
• Anatomical response was similar between treatments, with a reduction in central retinal thickness of -123.9 microns for ONS-5010 treated eyes and -127.3 microns for the ranibizumab group
• ONS-5010 was generally well-tolerated with overall ocular adverse event rates comparable to ranibizumab, with no cases of retinal vasculitis reported in either study arm. The most commonly reported adverse event (AE) was conjunctival hemorrhage, which occurred in 5 (2.5%) participants in each group.
• Safety results demonstrated across the full duration of NORSE EIGHT are consistent with previously reported safety results from the NORSE ONE, NORSE TWO, and NORSE THREE clinical trials.
   

“The NORSE EIGHT results provide additional evidence to the retina community that ONS-5010 meets the expectations for an ophthalmic formulation of bevacizumab, without the challenges that can arise from using repackaged, off-label formulations available today," Dr. Kuppermann said in a company news release. "The reductions in central retinal thickness observed in the trial confirmed that ONS-5010 reduced fluid in the retina on par with ranibizumab, and I’ve been encouraged with the consistency of this treatment across all NORSE clinical studies."

“Based on the data seen to date, we continue to be encouraged by the potential of ONS-5010 for the treatment of wet AMD. We believe that the complete data set from all of our NORSE clinical trials supports the resubmission of our BLA in the United States for the treatment of wet AMD, which we remain on track to complete this quarter,” said Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics.

Based on the completed analysis of the 12-week results, Outlook Therapeutics plans to resubmit the Biologics License Application (BLA) application to the FDA for ONS-5010 in the first quarter of calendar 2025.

In the EU and the UK, ONS-5010/LYTENAVA (bevacizumab gamma) has already been granted Marketing Authorization. Outlook Therapeutics said it intends to continue efforts to begin launching in Europe in the first half of calendar 2025.