Outlook Therapeutics, Inc. recently presented pivotal safety and efficacy data from the Phase 3 NORSE TWO trial for ONS-5010, an investigational ophthalmic formulation of bevacizumab for use in wet age-related macular degeneration (wet AMD) and other retinal indications. ONS-5010 is an investigational ophthalmic formulation of the FDA-approved drug bevacizumab to be administered as an intravitreal injection.
The data presentation “Safety and Efficacy Results of ONS-5010, as Ophthalmic Bevacizumab, Phase 3 Pivotal Study of Monthly Intravitreal OS-5010 in Subjects with Wet AMD (NORSE TWO)” was given during the Retinal Subspecialty Day, AAO 2021 Annual Conference, Section X: Late Breaking Developments, Part II by Firas M. Rahhal, MD, Retina-Vitreous Associates Medical Group, Assoc. Clinical Professor of Ophthalmology, UCLA School of Medicine.
“If approved by the FDA, ONS-5010 will become the first and only on-label ophthalmic bevacizumab, which is very significant for thousands of patients needing anti-VEGF treatments to control their wet AMD,” said Dr. Rahhal. “It will be great for patients and their doctors to have more FDA-approved anti-VEGF options that are prepared specifically for intraocular use.”
The NORSE TWO Phase 3 pivotal trial enrolled a total of 228 wet AMD patients at 39 clinical trial sites in the United States. NORSE TWO was a superiority trial comparing the safety and efficacy of ONS-5010 ophthalmic bevacizumab dosed monthly against ranibizumab (LUCENTIS®) dosed according to the PIER regimen in the Lucentis labeling. Participants in the trial were treated for 12 months, with the primary endpoint at Month 11 being the difference in proportion of patients who gained at least 15 letters (3 lines) in best corrected visual acuity (BCVA). The key secondary endpoint was the mean change in BCVA from baseline to Month 11. NORSE TWO data showed a strong safety profile, results consistent with previously reported safety data for ONS-5010, and similar to safety levels reported in prior research for bevacizumab used off-label in ophthalmology.
The NORSE TWO pivotal data met both primary and secondary endpoints with statistically significant and clinically relevant results:
41.7% (p = 0.0052) ONS-5010 subjects gained ≥ 15 letters of vision
56.5% (p = 0.0016) ONS-5010 subjects gained ≥ 10 letters of vision
68.5% (p = 0.0116) ONS-5010 subjects gained ≥ 5 letters of vision
ONS-5010 subjects gained 11.2 letters (p = 0.0043) in BCVA
Results from NORSE TWO also demonstrated that ONS-5010 ophthalmic bevacizumab has a strong safety profile. In findings that are consistent with historical bevacizumab data reported in prior research, in all three ONS-5010 registration trials there was only one ocular inflammatory adverse event, which was treated topically and resolved without sequelae. The safety findings continue to support minimal ocular inflammation and safety signals consistent with what was previously reported in the 2011 CATT trial (National Eye Institute) and other large bevacizumab-controlled ophthalmic studies.
“With the positive results from NORSE TWO, we are confident that, if approved, ONS-5010 has the potential to become a valuable new tool in the armamentarium of therapies for wet AMD. If approved as the first on-label ophthalmic formulation of bevacizumab, ONS-5010 will enable patients to benefit from wider access and provide an attractive alternative for anti-VEGF treatment of wet AMD,” added C. Russell Trenary III, President and CEO of Outlook Therapeutics. “We are moving ahead with our plans to submit our BLA for wet AMD with the FDA in the first quarter of calendar 2022 and working with other global regulatory authorities to bring this important therapy to market.”
Outlook Therapeutics’ clinical program investigating ONS-5010 ophthalmic bevacizumab to treat wet AMD consists of three clinical trials – NORSE ONE, NORSE TWO, and NORSE THREE – all of which have now been completed. Based on the strong data from this clinical program, Outlook Therapeutics plans to submit a new BLA under the Public Health Service Act (PHSA) 351(a) regulatory pathway in the first quarter of calendar 2022. If the BLA is approved, it is expected to result in 12 years of marketing exclusivity in the US for ONS-5010 as the first and only ophthalmic formulation of bevacizumab approved by the FDA to treat wet AMD.
Full press release: ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeutics-presents-norse-two-phase-3-pivotal-safety
Source: Outlook Therapeutics