FDA Accepts Supplemental BLA for Faricimab for Treatment of Retinal Vein Occlusion

US Food and Drug Administration

The US Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) for faricimab-svoa (Vabysmo®) for the treatment of macular edema following retinal vein occlusion (RVO).¹

According to the release from Genentech, the sBLA is based on findings from the phase 3 BALATON and COMINO studies showing treatment with faricimab-svoa led to early and sustained improvements in vision and met the primary endpoint of noninferior visual acuity gains at 24 weeks compared to aflibercept.

“This acceptance brings us one step closer to delivering Vabysmo as a treatment for RVO, a disease that affects more than one million people in the United States and can cause severe and sudden vision loss,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development.¹ “If approved, this would the third indication for Vabysmo, the first bispecific antibody available for the treatment of retinal conditions that can cause blindness.”

The therapy targets and inhibits two disease pathways linked to several vision-threatening retinal conditions by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Previously, in January 2022, faricimab-svoa was approved for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME).

It is the only injectable eye medicine approved for wet AMD and DME by the FDA, with the option for treatments from 1 to 4 months apart in the first year following 4 initial monthly loading doses. The efficacy and safety profile of the therapy was supported by 4 large, global studies of more than 3,000 participants and extensive real-world experience, it is currently approved in 60 countries and more than 1 million doses have been distributed globally.²

In the BALATON and COMINO trials, patients were randomized 1:1 to receive 6 monthly injections of either faricimab-svoa (6.0 mg) or aflibercept (2.0 mg) for the first 20 weeks. From weeks 24 - 72, all patients received faricimab-svoa (6.0 mg) up to every 4 months, according to a personalized treatment interval dosing regimen and using a treat-and-extend approach.

The BALATON study included 553 patients with branch RVO, and the COMINO study included 729 patients with central retinal or hemiretinal vein occlusion. Each study’s primary endpoint is the change in best-corrected visual acuity (BCVA) from baseline at 24 weeks, with secondary endpoints including the change in central subfield thickness (CST) from baseline over time up to 24 weeks.

For both studies, the average vision gains from baseline were comparable with faricimab-svoa and aflibercept treatment. For patients in BALATON, vision gains were +16.9 eye chart letters in the faricimab-svoa arm and +17.5 letters in the aflibercept arm at 24 weeks. For those in COMINO, vision gains were +16.9 letters in the faricimab-svoa arm and +17.3 letters in the aflibercept arm at 24 weeks.

Secondary endpoints showed that faricimab-svoa achieved rapid and robust drying of retinal fluid, comparable to aflibercept, as measured by the reduction in central subfield thickness (CST) from baseline. In BALATON, the CST reductions from baseline at 24 weeks were 311.4 µm in the faricimab-svoa arm and 304.4 µm in the aflibercept arm; for COMINO, the CST reductions from baseline at 24 weeks were 461.6 µm in the faricimab-svoa arm and 448.8 µm in the aflibercept arm.

Additionally, the BALATON study showed that 34% of patients treated with faricimab-svoa had an absence of macular leakage compared to 21% of aflibercept patients at 24 weeks; the COMINO study showed the rates were 44% for those treated with faricimab-svoa and 30% for those treated with aflibercept at 24 weeks. The safety profile was consistent with previous trials and across study arms, with the most common adverse reaction being conjunctival hemorrhage (3%).

Both studies are ongoing and data from weeks 24 to 72 aims to assess the potential of faricimab-svoa to extend dosing intervals up to every 4 months. Data from the BALATON and COMINO studies will be submitted to other global health authorities for approval for the treatment of macular edema following RVO, according to the release.

References

1. Genentech: Press releases: Monday, May 8, 2023. Genentech: Press Releases | Monday, May 8, 2023. Accessed May 9, 2023. https://www.gene.com/media/press-releases/14991/2023-05-08/fda-accepts-application-for-genentechs-v.
2. Genentech: Press releases: Wednesday, Oct 26, 2022. Genentech: Press Releases | Wednesday, Oct 26, 2022. Accessed May 9, 2023. https://www.gene.com/media/press-releases/14969/2022-10-26/positive-topline-phase-iii-results-show-.