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Outlook Therapeutics , Inc. Logo Outlook Therapeutics Reports Positive Efficacy and Safety Data from Pivotal Phase 3 NORSE TWO Trial of ONS - 5010 / LYTENAVA TM ( bevacizumab - vikg ) for the Treatment of Wet AMD August 3 , 2021 • In NORSE TWO , ONS - 5010 achieved statistically significant and clinically relevant primary ( p = 0.0052 ) and key secondary ( p = 0.0043 ) efficacy endpoints with 41 % of subjects gaining at least 15 letters • In NORSE TWO , ONS - 5010 was safe and well tolerated • Management to host conference call and webcast today at 8:00 a.m. ET ISELIN , N.J. , Aug. 03 , 2021 ( GLOBE NEWSWIRE ) -- Outlook Therapeutics , Inc. ( Nasdaq : OTLK ) , a biopharmaceutical company working to develop and launch the first FDA - approved ophthalmic formulation of bevacizumab for use in retinal indications , today announced positive clinical and highly statistically significant top - line results from its pivotal Phase 3 NORSE TWO safety and efficacy trial evaluating ONS - 5010 / LYTENAVA ™ ( bevacizumab ) for treatment of neovascular age - related macular degeneration ( wet AMD ) . Outlook Therapeutics will host conference call and webcast today , August 3 , 2021 , at 8:00 a.m. ET ( details below ) to discuss the results of the study . " We are delighted with the compelling results observed in NORSE TWO , which represent a significant and potentially transformational milepost for patients suffering from wet AMD . We plan on bringing the first ophthalmic formulation of bevacizumab to market , if approved . Currently there are a vast number of off - label injections of bevacizumab to treat retinal disease in the United States , and we want to offer an alternative for patients and retinal surgeons that is approved and formulated and packaged specifically for wet AMD . The successful completion of this trial is the final step needed in our clinical evaluation of ONS - 5010 to enable us to submit a Biologics License Application to the FDA in the first calendar quarter of next year , " said C. Russell Trenary III , President and CEO of Outlook Therapeutics . " I would like to thank the trial participants and investigators , our partners , and our employees for their contributions to NORSE TWO . " The NORSE TWO pivotal Phase 3 clinical trial enrolled a total of 228 subjects with wet AMD across 39 clinical trial sites in the United States . Participants in the trial were treated for 12 months . The primary endpoint for the study was the proportion of patients who gain at least 15 letters in the best corrected visual acuity ( BCVA ) at 11 months . The trial compared ONS - 5010 dosed monthly to LUCENTIS® , which was dosed as one of the regimens listed in the LUCENTIS ® label ( i.e. , patients were treated monthly for the first three months followed by less frequent dosing ; the PIER regimen ) . The key secondary endpoint for NORSE TWO was the mean change in the BCVA through 11 months . " In meeting both the primary and key secondary endpoints in NORSE TWO with highly significant clinically relevant results , we have achieved the requirements agreed upon with the FDA , and when combined with our previously reported clinical trial results , this completes the clinical package necessary for the submission of our BLA . We look forward to working with the FDA and other global authorities to potentially bring this new option to providers , clinicians , and patients as quickly as possible as an alternative to off - label IV repackaged bevacizumab , that is not approved for ophthalmic use , " added Terry Dagnon , Chief Operating Officer of Outlook Therapeutics . Top - line data from NORSE TWO showed that ONS - 5010 bevacizumab - vikg met the primary and key secondary endpoint for efficacy with clinically impactful change observed for treated patients . The NORSE TWO primary endpoint difference in proportion of subjects gaining at least 15 letters BCVA was met and was highly statistically significant and clinically relevant . In the intent - to - treat ( ITT ) primary dataset , the percentage of patients who gained at least 15 letters who were treated with ranibizumab was 23 % , and the percentage of patients who gained at least 15 letters who were treated with bevacizumab - vikg was 41 % ( p 0.0052 ) . The primary endpoint was also statistically significant and clinically relevant in the secondary per - protocol ( PP ) dataset ( p = 0.04 ) where the percentages were almost identical , at 24 % with ranibizumab and 41 % with bevacizumab - vikg . The key secondary endpoint BC VA score change from baseline to month 11 in the primary ITT dataset was also highly statistically significant and clinically relevant ( p = 0.0043 ) . A mean change in BCVA was observed with ranibizumab of 5.8 letters and the mean change with bevacizumab - vikg was 11.2 letters . The results were also statistically significant in the secondary PP dataset ( p = 0.05 ) with a mean change in letters with ranibizumab of 7.0 letters and with bevacizumab - vikg 11.1 letters . The safety results demonstrated in NORSE TWO are consistent with previously reported safety results from Outlook Therapeutics ' NORSE ONE and NORSE THREE clinical trials . Following exposure to bevacizumab - vikg , there was only one subject who reported an adverse event of ocular inflammation in all three trials . In NORSE TWO , there was only a single related ocular serious adverse event reported in the bevacizumab - vikg trial 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 . " As an Investigator in the NORSE TWO trial , I find these clinically relevant results , most notably the 41 % of ONS - 5010 patients who gained three lines of vision , to be very exciting for the retina community and confirm what we all had hoped to see in the investigation of ONS - 5010 to treat wet AMD . Clearly , in this trial ONS - 5010 appears to be a potential option as an ophthalmic bevacizumab , " commented Firas Rahhal , MD , Senior Partner at Retina - Vitreous Associates Medical Group and Associate Clinical Professor of Ophthalmology at the UCLA School of Medicine . “ As a clinician , I look forward to supporting the submission for FDA approval and including ONS - 5010 as an important treatment option for wet AMD patients , if approved . " ONS - 5010 ( bevacizumab ) registration clinical trial program Outlook Therapeutics ' wet AMD ONS - 5010 clinical program for the planned BLA consists of three clinical trials : NORSE ONE , a proof - of - concept clinical experience trial in wet AMD patients ; NORSE TWO , the pivotal Phase 3 wet AMD trial ; and NORSE THREE , a supplemental safety study in patients with wet AMD and other retina diseases undertaken to ensure that a sufficient number of patients have been dosed with ONS - 5010 to support the BLA submission . Results from NORSE ONE and NORSE THREE demonstrated positive proof - of - concept and a safety profile consistent with that of prior published research on bevacizumab for ophthalmic use . NORSE TWO provided pivotal data that demonstrated positive and highly statistically