The FDA has set a PDUFA goal date of August 29, 2023. Bevacizumab-vikg, if approved, is expected to receive 12 years of regulatory exclusivity in the United States.
Outlook Therapeutics Inc. today announced that the FDA has accepted its Biologics License Application (BLA) for bevacizumab-vikg (ONS-5010/Lytenava), an investigational ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD).
According to a news release, the FDA set a Prescription Drug User Fee Act (PDUFA) goal date of August 29, 2023. Bevacizumab-vikg, if approved, is expected to receive 12 years of regulatory exclusivity in the United States.
“This BLA acceptance and PDUFA date are significant milestones in our mission to offer clinicians and their patients the first and only on-label, ophthalmic bevacizumab to treat wet AMD,” Russell Trenary, president and CEO of Outlook Therapeutics,” said in a statement.
Bevacizumab-vikg is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no currently approved ophthalmic formulations of bevacizumab are available, clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies, products that have known risks of contamination and inconsistent potency and availability.
If approved, bevacizumab-vikg can replace the need to use unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.
Trenary also noted that if approved, bevacizumab-vikg would meet the FDA requirements for use as an ophthalmic injectable.
“We estimate that approximately 50% of the millions of anti-VEGF injections in ophthalmology are off-label compounded bevacizumab that is administered with no FDA-approved labeling,” he said in the news release. “That product configuration does not meet the same standards we must achieve to earn FDA approval in ophthalmology. We hope to enhance the standard of care in the anti-VEGF space, and we are proud of the entire team and our clinical partners and advisors for bringing ONS-5010 to this point in its journey towards FDA approval.”
Terry Dagnon, chief operations officer of Outlook Therapeutics, noted that the company is pleased the FDA has begun its review of its application.
“ONS-5010 is designed and manufactured to be fully compliant with the FDA’s criteria for ophthalmic intravitreal biologics and we are excited about the prospect of filling the public health need for an FDA-approved ophthalmic formulation of bevacizumab,” Dagnon added in the news release.
In anticipation of possible FDA approval next year and as part of its multi-year commercial planning process, the company and AmerisourceBergen recently announced a strategic commercialization agreement to expand the company’s reach for connecting to retina specialists and their patients.
According to the news release, AmerisourceBergen will provide third-party logistics (3PL) services and distribution, as well as pharmacovigilance services in the United States. Through this agreement, Outlook Therapeutics expects to increase market access and efficient distribution of bevacizumab-vikg, while not duplicating services provided by AmerisourceBergen, thereby decreasing Outlook’s otherwise needed expense for those same services.
The company also noted that it also established partnerships with FUJIFILM Diosynth Biotechnologies for drug substance manufacturing, and with drug product manufacturer Ajinomoto Bio-Pharma Services for finished drug product.
In addition to the U.S. filing, Outlook Therapeutics is also developing registration documents on a parallel path for approvals in Europe and expects to submit them in the fourth quarter of 2022. Outlook Therapeutics is assessing both direct commercialization and partnering in Europe and Asia on a country-by-country basis.
NORSE Registration Clinical Program for Wet AMD
NORSE ONE was a clinical experience trial involving 61 wet AMD participants at nine trial sites in Australia. NORSE ONE compared bevacizumab-vikg to ranibizumab (LUCENTIS®) as a treatment for wet AMD and showed the first markers of efficacy and safety in humans for ONS-5010 ophthalmic bevacizumab. In the trial, bevacizumab-vikg efficacy and safety data were consistent with historical published studies of bevacizumab in ophthalmology, and NORSE ONE also supported the trial design and inclusion/exclusion criteria for NORSE TWO, the pivotal Phase 3 registration clinical trial.
The NORSE TWO Phase 3 pivotal trial enrolled a total of 228 wet AMD patients at 39 clinical trial sites in the United States. It was designed as a superiority study comparing the safety and efficacy of bevacizumab-vikg ophthalmic bevacizumab dosed monthly against ranibizumab (Lucentis) dosed according to the PIER dosing regimen described in the Lucentis label. The trial data met both the primary and secondary endpoints with high statistical significance and clinical relevance. For its primary endpoint, 41.7% (p = 0.0052) of patients gained ≥ 15 letters of vision, and for its secondary endpoints, 56.5% (p = 0.0016) of patients gained ≥ 10 letters of vision and 68.5% (p = 0.0116) gained ≥ 5 letters. The key secondary endpoint, mean change in BCVA from baseline to Month 11, was 11.2 letters gained (p = 0.0043) compared to 5.8 letters gained in the ranibizumab arm. The NORSE TWO data also showed that the drug was well-tolerated, consistent with previously reported data for ONS-5010 and prior research.
NORSE THREE was an open-label safety study of bevacizumab-vikg in 197 patients conducted in the United States to provide the necessary number of retina patients dosed with bevacizumab-vikg 5010 to complete the safety requirements for the BLA submission.
Safety results across the first three NORSE trials demonstrated a strong benefit-to-risk safety profile. Across all three bevacizumab-vikg 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 (≥ 5%) reported in patients receiving bevacizumab-vikg was conjunctival hemorrhage associated with the needle injection procedure (5%).