Outlook Therapeutics, Inc. (Nasdaq: OTLK) has announced the completion of enrollment in its NORSE EIGHT clinical trial, a critical step toward the potential U.S. approval of ONS-5010/LYTENAVA™ (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD). The company expects to report topline results from the trial in the fourth quarter of calendar year 2024.
The NORSE EIGHT trial is a randomized, controlled, parallel-group, masked, non-inferiority study designed to evaluate the efficacy and safety of ONS-5010 compared to ranibizumab in treatment-naive patients with wet AMD. The trial enrolled patients who were randomized 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 of the NORSE EIGHT trial is the mean change in best corrected visual acuity (BCVA) from baseline to week 8. This endpoint is crucial for assessing whether ONS-5010 is non-inferior to ranibizumab in improving vision in patients with wet AMD.
Regulatory Pathway and Potential Commercialization
The NORSE EIGHT trial is the subject of a Special Protocol Assessment (SPA) agreement with the FDA. According to Outlook Therapeutics, successful completion of this trial would satisfy the FDA’s requirement for a second adequate and well-controlled clinical trial to address the clinical deficiency identified in the Complete Response Letter (CRL) previously issued for ONS-5010.
Russell Trenary, President and Chief Executive Officer of Outlook Therapeutics, expressed gratitude to the patients, clinical site teams, and the company's staff for their contributions to completing enrollment in the trial. He stated, "We remain confident in the potential of ONS-5010, if approved, to meet the needs of retina specialists, patients, and payers."
ONS-5010: An Ophthalmic Formulation of Bevacizumab
ONS-5010/LYTENAVA™ (bevacizumab-vikg) is an ophthalmic formulation of bevacizumab, a recombinant humanized monoclonal antibody (mAb) that selectively binds to all isoforms of human vascular endothelial growth factor (VEGF). By neutralizing VEGF’s biologic activity, bevacizumab reduces endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.
LYTENAVA™ (bevacizumab gamma) has already received marketing authorization in the European Union and the United Kingdom for the treatment of wet AMD. Outlook Therapeutics is preparing for a commercial launch in these regions in the first half of calendar year 2025.
Addressing Unmet Needs in Wet AMD Treatment
Wet AMD is a leading cause of vision loss in individuals over the age of 60. The condition is characterized by the abnormal growth of blood vessels in the macula, the central part of the retina responsible for sharp, central vision. Current treatments, such as ranibizumab and aflibercept, require frequent intravitreal injections, posing a burden on patients and healthcare systems. If approved, ONS-5010 could provide an additional treatment option for wet AMD, potentially reducing the treatment burden and improving patient outcomes. The planned resubmission of the Biologics License Application (BLA) for ONS-5010 is slated for Q1 2025.
