Faricimab satisfies primary study endpoint in TENAYA and LUCERNE trials

Guymer

Reviewed by Robyn Guymer, PhD, MBBS

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.

This drug, as Guymer explained, is the first bispecific antibody designed for intraocular use that may synergistically promote vascular stability and reduce treatment burden through extended durability in patients with neovascular AMD.

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.

Results
The TENAYA and LUCERNE trials included 671 and 658 patients, respectively.

The investigators reported, “Both studies met the primary endpoint, with faricimab demonstrating every 12-week-dosing intervals or longer in about 80% of patients during the first year.

The durability of the treatment was demonstrated up to every 16 weeks at week 48. Meaningful reductions in the CST with faricimab up to every 16 weeks were comparable to aflibercept dosed every 8 weeks through week 48.

Faricimab was well tolerated with few intraocular events in 2.0% of patients randomized to faricimab and 1.2% assigned to aflibercept. No vasculitis or occlusive retinitis developed.

A noteworthy focus of the TENAYA and LUCERNE trials was the examination of individualized treatment tailored to individual patients with an eye toward reducing the treatment burden and maintaining efficacy compared with aflibercept dosed every 8 weeks.

Both trials will continue out to 2 years to continue the evaluations of the efficacy, durability, and safety of faricimab.

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Robyn Guymer, PhD, MBBS
E: rh.guymer@unimelb.edu.au
This article is adapted from Guymer’s presentation at the Association for Research in Vision and Ophthalmology’s 2021 virtual annual meeting. She is a consultant to Hoffmann-LaRoche.