Clinical Experience Trial (NORSE ONE)
NORSE ONE, the first registration clinical trial in our clinical program evaluating ONS-5010 to treat wet AMD, is a clinical experience trial. In August 2020 we reported topline results and positive proof-of-concept data for safety and efficacy. In this initial clinical experience trial, we saw the positive trends in efficacy in 3-line visual acuity gains we expected, and ONS-5010 was well-tolerated in this study. Importantly, it showed no ocular adverse events related to inflammation. The results support the established design, inclusion criteria and protocol for NORSE TWO, the pivotal Phase 3 clinical trial evaluating ONS-5010 for treatment of wet AMD. Our initial clinical experience trial was conducted in Australia and compares ONS-5010 with an alternate dosing regimen of ranibizumab (LUCENTIS®).
Pivotal Phase 3 Trial (NORSE TWO)
NORSE TWO, the second of two registration clinical trials in our clinical program for ONS-5010 to treat wet AMD, is our pivotal trial. We reported positive topline efficacy and safety data in August 2021. In the trial, ONS-5010 achieved highly statistically significant and clinically relevant primary data (p = 0.0052) and key secondary efficacy endpoints (p = 0.0043), with 41% of subjects gaining at least 15 letters of BVCA. NORSE TWO enrolled 228 participants at 39 clinical trial sites across the United States. Participants in the trial were treated for 12 months. The primary endpoint for the study was the difference in proportion of patients who gained at least 15 letters in the best corrected visual acuity (BCVA) at 11 months for ONS-5010 dosed monthly, compared to LUCENTIS®, which was dosed as one of the regimens listed in the Lucentis label (i.e., patients are treated monthly for the first 3 months followed by less frequent dosing; the PIER regimen). . The safety results demonstrated in NORSE TWO are consistent with previously reported safety results from our NORSE ONE and NORSE THREE clinical trials. Following exposure to bevacizumab-vikg, there was only one subject that reported an adverse event of ocular inflammation in all three studies. In NORSE TWO, there was only a single related ocular serious adverse event reported in the bevacizumab-vikg study arm, which resolved and no unanticipated safety signals were detected. The most common ocular adverse event was intravitreal injection-related hemorrhage in the tissues on the surface of the eye (conjunctival hemorrhage) that resolved without any sequela. The ONS-5010 safety database continues to be consistent with previously published results for bevacizumab, such as in the 2011 CATT clinical trial. Together with the results of NORSE ONE and NORSE THREE, data from our pivotal NORSE TWO trial are expected to be sufficient to form the basis for a new BLA filing with the FDA in the first calendar quarter of 2022. We will submit ONS-5010 for approval under the PHSA 351(a) regulatory pathway for new biologics.
Safety Trial (NORSE THREE)
Our third clinical trial investigating ONS-5010 for treatment of wet AMD, NORSE THREE, is an open-label safety study that was conducted to ensure that an adequate number of safety exposures to ONS-5010 are available for the initial BLA regulatory filing. We reported a positive safety profile from this trial in March 2021, with no reports of ocular inflammation.
Branch Retinal Vein Occlusion
Outlook Therapeutics intends to initiate NORSE FOUR, a registration clinical trial that will evaluate ONS-5010 for use in treating BRVO.
Diabetic Macular Edema
Outlook Therapeutics also intends to commence NORSE FIVE and NORSE SIX, two registration clinical trials to evaluate ONS-5010 in treating DME.
Regulatory Approval Plans
Our successful Phase 3 clinical program in wet AMD is expected to support our plans to submit for regulatory approval of ONS-5010 in multiple markets. Because there is currently no bevacizumab approved for ophthalmic indications in the United States, we will file ONS-5010 with the FDA as a new BLA under the PHSA 351(a) regulatory pathway, not as a biosimilar.