Outlook Therapeutics is expected to submit a BLA to the FDA for the investigative ophthalmic bevacizumab-vikg formulation (ONS-5010).
In light of the new year, all eyes are on the next drug approvals to change the landscape of a specialty. For ophthalmology, faricimab for the treatment of both neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) is waiting on approval from the US Food and Drug Administration (FDA).
But, there is more going on in the first quarter of 2022, as a Biologics License Application is expected to be submitted to the FDA for the investigative ophthalmic bevacizumab-vikg formulation (ONS-5010).
Outlook Therapeutics is intending to file the BLA for bevacizumab in the treatment of wet age-related macular degeneration (wet-AMD) and other retinal diseases, administered as an intravitreal injection. The BLA is expected to note commercialization of ONS-5010 will include both vial and prefilled syringe formulations.
Wet AMD is the leading cause of vision loss among patients aged 50 years and older. Currently, there are no approved ophthalmic formulations for bevacizumab available, so its use is considered off-label. However, despite the lack of approval for ophthalmic use, bevacizumab is noted to have a history of safety and efficacy from prior data.
Specifically, bevcizumab-vikg is a recombinant humanized monoclonal antibody that selectively binds to all isoforms of human vascular endothelial growth factor (VEGF). Following intravitreal injection, it neutralizes the biologic activity of VEGF through a steric blocking of the binding of VEGF to its receptors Fit-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells.
Data from Outlook Therapeturics reported unapproved repackaged intravenous (IV) bevacizumab from pharmacy compounders accounts for nearly 50% of all wet AMD prescriptions in the United States.
In data presented at the American Academy of Ophthalmology 2021 Meeting, findings from the phase 3 NORSE 2 were imperative in determining a high efficacy and safety profile among patients with wet AMD. The superiority pivotal trial assessed 12-month efficacy and safety of ONS-5010 1.25 monthly intravitreal injections versus ranibizumab in the patient population.
Inclusion criteria included active, primary choroidal neovascularization (CNV) due to wet AMD and treatment-naive with best corrected visual acuity (BCVA) scores between 20/50 and 20/320. Main outcomes included the proportion of patients to gain ≥15 letters in BCVA and mean change in BCVA from baseline to month 11.
Randomization to ranibizumab IVI gave participants sham injections at month 4, 5, 7, 8, 10, and 11, with adverse event follow-up after month 12. Trial population included 228 patients randomized to ONS-5010 (n = 113) or ranibizumab (n = 115), with 103 and 95 patients completing the trial, respectively.
Data show 41.7% of patients in the ONS-5010 intent-to-treat arm met the primary outcome of ≥15 BCVA letter score improvement. Additionally, 41.0% of patients in the ONS-5010 per protocol arm reached the primary endpoint.
In comparison, 23.1% (P = .0052) and 24.7% (P = .0499) of intent-to-treat and per-protocol patients receiving ranibizumab met the endpoint, respectively. Investigators observed statistically-significant differences in the rate of ONS-5010 treatment achieving primary endpoint in months 5, 6, and 12 of the assessment.
Specifically, patients on intent-to-treat ONS-5010 reported 11.2 mean change in BCVA letter score and per protocol ONS-5010 reported 11.1 mean change in BCVA letter score. In comparison, intent-to-treat and per protocol ranibizumab patients reached 5.8 and 7.0 mean improvements in BCVA, respectively.
Safety data was consistent with previous NORSE trials, with ≥1 adverse event observed in 75.2% of patients on ONS-5010 and 73.9% of ranibizumab.
Overall, study investigators led by Firas M. Rahhal, MD, Associate Clinical Professor of Ophthalmology at UCLA School of Medicine, as a result concluded that these findings strongly support a BLA filing for bevacizumab in the treatment of wetAMD.