Outlook Therapeutics Completes 12-Week Analysis of NORSE EIGHT Trial for ONS-5010 in Wet AMD

Outlook Therapeutics has finalized the analysis of 12-week safety and efficacy data from the NORSE EIGHT trial, which evaluated ONS-5010 as a treatment for wet age-related macular degeneration (AMD). The results demonstrate noninferiority to ranibizumab and reinforce ONS-5010's potential as a viable treatment option for wet AMD.

Key Findings from the NORSE EIGHT Trial

Efficacy Results

       • Best Corrected Visual Acuity (BCVA):

               • ONS-5010 (1.25 mg) showed a +5.5 letter gain in BCVA at week 12.

               • Ranibizumab (0.5 mg) showed a +6.5 letter gain in BCVA.

                • The difference in mean BCVA between ONS-5010 and ranibizumab was -1.009 letters (95% confidence interval: -2.865, 0.848).

       • Retinal Thickness Reduction:

         • ONS-5010 demonstrated mean reductions in retinal thickness of:

               • -106.6 microns at week 4.

               • -117.7 microns at week 8.

               • -123.9 microns at week 12.

         • Ranibizumab achieved slightly greater reductions, with:

               • -108.4 microns at week 4.

              • -120.9 microns at week 8.

              • -127.3 microns at week 12.

Safety Profile

       • ONS-5010 was well-tolerated, with ocular adverse event rates comparable to ranibizumab.

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

       • Safety outcomes were consistent with those observed in previous trials (NORSE ONE, NORSE TWO, and NORSE THREE).

Regulatory and Commercial Progress

Biologics License Application (BLA) Resubmission

Despite not meeting the pre-specified noninferiority endpoint at week 8, Outlook Therapeutics highlighted the positive trends across all time points in BCVA and retinal thickness. The company plans to resubmit the BLA for ONS-5010 to the U.S. FDA in the first quarter of 2025.

Lawrence Kenyon, CFO and interim CEO, expressed confidence in the data:

“We believe that the statistically significant 12-week results for ONS-5010 in NORSE EIGHT, combined with the complete NORSE EIGHT data set, confirms our successful NORSE TWO pivotal study and will support the resubmission of our BLA in the United States for the treatment of wet AMD.”

Global Expansion

ONS-5010 received approval in the European Union and United Kingdom in early 2024. Furthermore, the company intends to launch ONS-5010 in Europe in the first half of 2025.

Expert Perspectives

Julia A. Haller, MD, ophthalmologist-in-chief at Wills Eye Hospital and Outlook Therapeutics board member, shared her insights:

“The 3-month data from NORSE EIGHT provides additional evidence to confirm what retina specialists expected. The clinical trial continues to demonstrate that ONS-5010 injections result in immediate and sustained anatomic efficacy, with steady gains in visual acuity and reliable, consistent safety.” 

Conclusion

The NORSE EIGHT trial underscores the potential of ONS-5010 to provide a safe and effective alternative to off-label bevacizumab for treating wet AMD. As Outlook Therapeutics moves forward with its BLA resubmission and prepares for global commercialization, ONS-5010 could redefine the standard of care in retinal disease management.