Outlook Therapeutics announced preliminary topline results from its NORSE EIGHT clinical trial, evaluating ONS-5010 (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD). The study, a randomized, controlled, masked, non-inferiority trial, compared ONS-5010 to ranibizumab in newly diagnosed wet AMD patients. While the drug demonstrated a favorable safety profile and some improvement in vision, it failed to meet its primary endpoint.
The NORSE EIGHT trial randomized patients in a 1:1 ratio to receive either 1.25 mg of ONS-5010 or 0.5 mg of ranibizumab via intravitreal injections at day 0, week 4, and week 8. The primary endpoint was the mean change in best corrected visual acuity (BCVA) from baseline to week 8. The pre-specified non-inferiority endpoint, set forth in the special protocol assessment (SPA) with the FDA, was not met. The difference in the means between the ONS-5010 and ranibizumab arms was -2.257 BCVA letters with a 95% confidence interval of (-4.044, -0.470). The lower bound of the pre-specified non-inferiority margin in the SPA was -3.5 at a 95% confidence interval, thus the hypothesis of noninferiority was not met (p>0.025).
Efficacy and Safety Results
In the intent-to-treat (ITT) primary dataset, the NORSE EIGHT trial demonstrated a mean +4.2 letter improvement in BCVA in the ONS-5010 arm and a +6.3 letter improvement in BCVA in the ranibizumab arm. The p-value was 0.0863. ONS-5010 was generally well-tolerated, with overall ocular adverse event rates comparable to ranibizumab. The safety results were consistent with previously reported safety results from the NORSE ONE, NORSE TWO, and NORSE THREE clinical trials, with no cases of retinal vasculitis reported in either study arm.
Next Steps for ONS-5010
Outlook Therapeutics plans to resubmit the Biologics License Application (BLA) for ONS-5010 in the first quarter of calendar 2025, pending the completion of analysis of the final results of NORSE EIGHT. The month 3 data from NORSE EIGHT is being collected and is expected to be available in January 2025. Remediation of the Chemistry, Manufacturing and Controls (CMC) comments in the Complete Response Letter (CRL) is complete and has been closely aligned with the FDA in type C and type D meetings.
LYTENAVA™ in Europe
In the European Union and the United Kingdom, ONS-5010/LYTENAVA™ (bevacizumab gamma) has already been granted Marketing Authorization. Outlook Therapeutics intends to continue efforts to begin launching in Europe in 2025 either directly or with a licensing partner. Discussions with potential licensing partners for markets outside of the United States are ongoing.
About ONS-5010/LYTENAVA™
ONS-5010/LYTENAVA™ (bevacizumab-vikg, bevacizumab gamma) is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. Bevacizumab-vikg is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells.
