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Bevacizumab-vikg was associated with statistically significant improvements in patient BCVA scores over a period of 12 months, according to phase 3 findings.
Investigative ophthalmic bevacizumab-vikg formulation (ONS-5010) significantly improved visual acuity versus ranibizumab in patients with wet age-related macular degeneration (AMD) over 12 months, according to phase 3 NORSE findings.
In new pivotal data presented by Firas M. Rahhal, MD, of the Retinal-Vitreous Associates Medical Group and Associate Clinical Professor of Ophthalmology at UCLA School of Medicine, at the American Academy of Ophthalmology (AAO) 2021 Meeting in New Orleans, the Outlook Therapeutics anti-VEGF injection therapy bettered a marketed competitor in efficacy outcomes while reporting a similar safety profile.
The findings may implicate a potential new regulatory use of the bevacizumab formulation in ophthalmic disease in the US.
Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds with high affinity to all isoforms of VEGF-A.
The phase 3 superiority pivotal trial assessed 12-month efficacy and safety of ONS-5010 1.25 monthly intravitreal injections (IVIs) versus ranbizumab IVIs in patients with wet AMD. Study eyes to have met inclusion criteria featured active, primary choroidal neovascularization (CNV) due to wet AMD; they were treatment-naïve, and feature best corrected visual acuity (BCVA) scores between 20/50 and 20/320.
Rahhal and colleagues sought outcomes of proportion of patients to gain ≥15 letters in BCVA, mean change in BCVA from baseline to month 11, and the frequency and incidence of adverse events in treated patients.
Patients randomized to ranibizumab IVI were given sham injections at months 4, 5, 7, 8, 10, and 11. Adverse event follow-up assessment was conducted after month 12.
The trial population included 228 patients randomized to either ONS-5010 (n = 113) or ranibizumab (n = 115); 103 and 95 patients from each arm completed the trial, respectively. Just 5 and 3 patients discontinued treatment due to an adverse event, respectively. Patient demographics were similar at baseline.
Investigators observed 41.7% of patients in the ONS-5010 intent-to-treat (ITT) arm reach the primary outcome of ≥15 BCVA letter score improvement at 12 months; among patients in the ONS-5010 per protocol arm, 41.0% reached the primary endpoint as well. Comparatively, just 23.1% (P = .0052) and 24.7% (P = .0499) of ITT and per protocol patients receiving ranibizumab achieved the endpoint, respectively.
Rahhal and colleagues observed statistically-significant differences in rate of ONS-5010-treated achieving the primary endpoint versus ranibizumab patients in months 5, 6, and 12 of the assessment. “There is a continual, gradual improvement after those first 3-4 months, out to 11 months,” Rahhal said.
Patients on ITT and per protocol ONS-5010 additionally reported 11.2 and 11.1 mean change in BCVA letter scores, respectively, at the study endpoint. Comparatively, ITT and per protocol ranibizumab patients achieved just 5.8 (P = .0043) and 7.0 (P = .05) improvements, respectively. Statistically significant differences between the treatment arms were observed from month 5 through month 11.
Investigators also observed safety results consistent with those observed in the NORSE 1 and NORSE 3 trials; ≥1 adverse event was observed in 75.2% of patients on ONS-5010, and 73.9% of patients on ranibizumab. Serious adverse event rates (12.4% vs 13.9%) and ocular serious adverse event rates (0.9% vs 0.0%) were similar in the treatment arms, respectively.
Rahhal concluded the findings “strongly support” a Biologics License Application (BLA) filing with the US Food and Drug Administration (FDA) for bevacizumab in treating wet AMD. In fact, Outlook Therapeutics intends to file a BLA in the first quarter of 2022.
The study, “Safety and Efficacy Results of ONS-5010, An Ophthalmic Bevacizumab, from Phase 3 Study of Monthly Intravitreal ONS-5010 In Subjects with Wet AMD (NORSE 2),” was presented at AAO 2021.