ONS 5010 filed with FDA for wet age-related macular degeneration.- Outlook Therapeutics

If approved, Lytenava (bevacizumab-vikg) could replace the current practice of using unapproved repackaged IV bevacizumab sourced from compounding pharmacies for the treatment of wet AMD.

The BLA submission is based on the totality of data from Outlook Therapeutics’ wet AMD clinical program for ONS 5010, which consists of three completed registration clinical trials: NORSE ONE, NORSE TWO and NORSE THREE. NORSE ONE was a clinical experience trial involving 61 wet AMD participants at nine trial sites in Australia. It compared ONS 5010 to ranibizumab (LUCENTIS) as a treatment for wet AMD. NORSE ONE showed the first markers of efficacy and safety in humans for ONS 5010 ophthalmic bevacizumab. In the trial, ONS-5010 efficacy and safety data were consistent with historical published studies of bevacizumab in ophthalmology. NORSE ONE also supported the trial design and inclusion criteria established for NORSE TWO, the pivotal Phase III registration clinical trial.

The NORSE TWO Phase III pivotal trial enrolled a total of 228 wet AMD patients at 39 clinical trial sites in the United States. It was a superiority trial design comparing the safety and efficacy of ONS 5010 ophthalmic bevacizumab dosed monthly against ranibizumab (LUCENTIS) dosed according to the PIER dosing regimen in the LUCENTIS label. The trial data met both their primary and secondary endpoints with high statistical significance and clinical relevance. For its primary endpoint, 41.7% (p = 0.0052) of patients gained at least 15 letters of vision, and for its secondary endpoints 56.5% (p = 0.0016) of subjects gained at least 10 letters of vision and 68.5% (p = 0.0116) gained at least 5 letters. The key secondary endpoint was also met: mean change in BCVA from baseline to Month 11, which was 11.2 letters gained (p = 0.0043). The NORSE TWO data also showed a strong safety profile consistent with previously reported data for ONS 5010 and prior research.

NORSE THREE was an open-label safety study of ONS 5010 in 197 patients conducted in the United States to provide the necessary number of retina patients dosed with ONS 5010 to complete the requirements of the BLA. Safety results across the three NORSE trials demonstrated a strong benefit-to-risk safety profile. Across all three ONS-5010 registration trials, there was only one ocular inflammation adverse event, which was reported in NORSE TWO; the event was treated topically and resolved without sequelae. The most common adverse reaction (at least 5%) reported in patients receiving ONS 5010 was conjunctival hemorrhage related to the injection procedure (5%). These 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 adequate and well-controlled ophthalmic studies of bevacizumab.