NORSE EIGHT Trial Results: ONS-5010 for Wet AMD

Outlook Therapeutics shared results from the NORSE EIGHT clinical trial at the Hawaiian Eye and Retina 2025 Meeting. The findings were presented by Baruch D. Kuppermann, MD, PhD, of the Gavin Herbert Eye Institute at the University of California, Irvine.

The presentation, titled “ONS-5010 (bevacizumab-vikg) versus Ranibizumab for Neovascular Age-related Macular Degeneration: Results from the NORSE-EIGHT Noninferiority Randomized Trial,” focused on the 12-week safety and efficacy results for ONS-5010 in treating wet age-related macular degeneration (AMD).

Overview of the NORSE EIGHT Trial

The NORSE EIGHT trial was a randomized, controlled, parallel-group, masked, noninferiority study. It involved newly diagnosed wet AMD patients who were randomized in a 1:1 ratio to receive intravitreal injections of either:

• 1.25 mg ONS-5010, or

• 0.5 mg ranibizumab.

Participants received injections on Day 0, Week 4, and Week 8, 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.

Key Results and Highlights

BCVA Improvements:

• Baseline Mean BCVA:

• ONS-5010 group: 58.8 ETDRS letters

• Ranibizumab group: 59.9 ETDRS letters

• BCVA Improvements for ONS-5010:

• +3.3 letters at Month 1

• +4.2 letters at Month 2

• +5.5 letters at Month 3

• BCVA Difference:

• Mean BCVA difference between ONS-5010 and ranibizumab: -1.009 letters

• 95% Confidence Interval: (-2.865, 0.848)

• This met the noninferiority margin at Month 3 (P=0.0043), applying statistical parameters from the Week 8 primary endpoint.

Safety and Adverse Events:

• Overall Tolerability:

• ONS-5010 was well-tolerated with adverse event (AE) rates comparable to ranibizumab.

• No cases of retinal vasculitis were reported in either study arm.

• Most Common AE:

• Conjunctival hemorrhage, occurring in 5 participants (2.5%) in both groups.

• Anatomical Response:

• Reduction in central retinal thickness:

• ONS-5010 group: -123.9 microns

• Ranibizumab group: -127.3 microns

Trial Outcome:

• While ONS-5010 did not meet the prespecified noninferiority endpoint at Week 8 set forth in the FDA’s special protocol assessment, the safety results were consistent with findings from prior NORSE trials (NORSE ONE, NORSE TWO, and NORSE THREE).

Expert Perspectives

“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. 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." said Dr. Baruch D. Kuppermann.

“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,” commented Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics.

Future Plans and Regulatory Updates

FDA Resubmission:

• Outlook Therapeutics plans to resubmit its BLA for ONS-5010 in the first quarter of 2025.

EU and UK Approvals:

• ONS-5010/LYTENAVA (bevacizumab gamma) has already received Marketing Authorization in the EU and UK.

• Outlook Therapeutics aims to begin launching ONS-5010 in Europe during the first half of 2025.

The findings from the NORSE EIGHT trial reinforce the promise of ONS-5010 as a viable treatment option for wet AMD, with continued progress expected in its global regulatory journey.