FDA accepts Genentech’s BLA for faricimab for treatment of wet AMD and DME

On July 28, Genentech, a member of the Roche Group, announced the acceptance of their Biologics License Application (BLA) by the U.S. Food and Drug Administration (FDA) under Priority Review. Their BLA details faricimab for treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME). Additionally, the FDA accepted Genentech’s application for diabetic retinopathy.

“If approved, faricimab would be the first in a new class of eye medicines targeting two key pathways that drive retinal disorders, with the potential to offer durable vision outcomes with fewer eye injections than the current standard of care,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development.

In addition to the BLA, Genentech also has multiple studies underway for faricimab. AVONELLE X is an extension study of TENAYA and LUCERNE, which is assessing the long-term safety and efficacy of faricimab as treatment for wet AMD. RHONE X is an extension study of YOSEMITE and RHINE, which is measuring the safety and efficacy of faricimab as a treatment for DME. The COMINO and BALATON trials are currently evaluating the safety and efficacy of faricimab in patients with macular edema secondary to central retinal vein occlusion (RVO) and branch RVO.

TENAYA and LUCERNE trials

The results of the phase III TENAYA and LUCERNE trials showed that faricimab (Hoffman-La Roche) met the primary efficacy endpoints of noninferiority to aflibercept (Eylea, Regeneron Pharmaceuticals) in the change in the best-corrected visual acuity (BCVA), durability, and safety for treating patients with neovascular age-related macular degeneration (AMD), according to Robyn Guymer, a professor of ophthalmology at Melbourne University and deputy director of the Centre for Eye Research Australia in Melbourne.

These 2 clinical trials are large identical randomized, double-masked, investigations that are evaluating the dual inhibition of angiopoietin-2 and vascular endothelial growth factor-A by faricimab.

Patients in these 112-week studies were treatment-naïve and randomized 1:1 to faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses.

After the initial dosing and assessments of the disease activity, the patients receiving faricimab were treated at fixed intervals, i.e., every 16 weeks, every 12 weeks, or every 8 weeks.

The patients treated with faricimab then followed a personalized treatment interval, that is, a protocol-driven treat-and-extend regimen with interval adjustment that was based on individualized treatment responses as assessed by the prespecified anatomic and functional criteria at study drug dosing visits up to week 108.

The primary efficacy endpoint was the change in the BCVA compared with baseline averaged over weeks 40, 44, and 48 and compared with aflibercept.

The secondary safety endpoints were the proportions of patients treated every 8, every 12, and every 16 weeks; the proportion of patients who had increases of 15 letters or more or who did not have losses of 15 letters or more; and the changes in the BCVA and central subfield thickness (CST) over time.

The safety endpoints were the incidence and severity and non-ocular adverse events.

Read more: Study shows positive results in treatment of DME with faricimab

YOSEMITE and RHINE trials

The 1-year results of the ongoing 2-year YOSEMITE and RHINE trials showed favorable results for faricimab for treating diabetic macular edema (DME). The visual gains achieved with every-16-week dosing were non-inferior to those of aflibercept (Eylea, Regeneron Pharmaceuticals) dosed every 8 weeks.

The anatomic gains also favored faricimab compared with aflibercept. Faricimab also demonstrated a good safety profile with very low rates of inflammation. John Wells, MD, from the Palmetto Retina Center, West Columbia, South Carolina, presented the results at the Association for Research in Vision and Ophthalmology’s (ARVO) virtual 2021 annual meeting on behalf of the YOSEMITE and RHINE investigators.

The YOSEMITE and RHINE trials, which are identical, randomized double-masked studies compared the efficacy, durability, and safety of faricimab with aflibercept in patients with center-involving DME who were either treatment-naïve or received previous treatment with anti-VEGF therapy.

Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W) after 6 initial every-4-week Q4W doses; faricimab 6.0 mg treated according to a personalized treatment interval (PTI) based on the treat-and-extend concept after 4 initial very-4-week doses; or aflibercept 2.0 mg every 8 weeks after 5 initial every-4-week doses.

The primary efficacy endpoint was the mean change in the best-corrected visual acuity (BCVA) from baseline averaged over study weeks 48, 52, and 56. The secondary endpoints were the proportion of patients with a 2-step or more improvement in the Early Treatment Diabetic Retinopathy Diabetic Retinopathy Severity Scale (ETDRS-DRSS) from baseline, the proportion of patients with a 15 or greater gain in ETDRS letters from baseline, the change in central subfield thickness (CST) from baseline, and the proportion of patients in the PTI arm receiving doses every 4, every 8, every 12, or every 16 weeks at 1 year.

Read more: Faricimab satisfies primary study endpoint in TENAYA and LUCERNE trials

Related Content: Ophthalmology | AMD | Diabetic Macular Edema | Diabetic Retinopathy