- Data presented at Hawaiian Eye and Retina 2025 Meeting
- Results confirmed that intravitreal ONS-5010 provided early and sustained anatomic improvements, with steady gains in BCVA and reliable, consistent safety
- ONS-5010 demonstrated to be non-inferior to Lucentis at 4 and 12 weeks
- Company on track for anticipated BLA resubmission in calendar Q1 2025
Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company that achieved regulatory approval in the European Union (EU) and the United Kingdom (UK) for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD), announced the presentation of data from NORSE EIGHT at the Hawaiian Eye and Retina 2025 Meeting held January 18-24, 2025 in Kauai, HI.
As part of the 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 recently announced 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, non-inferiority 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.
“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. Kuppermann.
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 pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment with the U.S. Food and Drug Administration (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.
“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,” added 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 for ONS-5010 in the first quarter of calendar 2025.
For more information about the NORSE EIGHT study, visit clinicaltrials.gov and reference identifier NCT06190093.
In the EU and the UK, ONS-5010/LYTENAVA (bevacizumab gamma) has already been granted Marketing Authorization. Outlook Therapeutics intends to continue efforts to begin launching in Europe in the first half of calendar 2025.
About ONS-5010 / LYTENAVA (bevacizumab-vikg, bevacizumab gamma)
ONS-5010/LYTENAVA is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. LYTENAVA (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the European Union (EU) and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) for the treatment of wet AMD.
In the United States, ONS-5010/LYTENAVA (bevacizumab-vikg) is investigational.
Bevacizumab-vikg (bevacizumab gamma in the EU and UK) 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. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.