European Commission approves faricimab for treatment of wet AMD, DME

Roche’s treatment of faricimab is the first and only FDA-approved medicine targeting two distinct pathways, angiopoietin (Ang)-2 and vascular endothelial growth factor (VEGF)-A, that often cause retinal diseases that may cause visual loss.

Today, the European Commission (EC) approved faricimab (Roche), a bispecific antibody for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME). Faricimab is the first and only EC-approved drug to target two distinct pathways, Ang-2 and VEGF-A, that often cause retinal disease that may lead to visual loss.

“Many people with nAMD and DME struggle to keep up with the monthly eye injections and physician visits, often associated with current standards of care, and unfortunately their vision may suffer as a result of undertreatment,” said Prof. Ramin Tadayoni, MD, PhD, head of the ophthalmology department, Lariboisière, Saint-Louis and Rothschild Hospitals, Paris, France, and European Society of Retina Specialists (EURETINA) president elect.

“For people in Europe living with these conditions, today’s approval offers the first new mechanism of action in over a decade; one which could improve and protect their vision with fewer injections over time,” continued Tadayoni in a press release.

Faricimab met its primary endpoints for a variety of studies: TENAYA and LUCERNE and its extension study AVONELLE X, which assessed the long-term safety and efficacy of faricimab for the treatment of wet AMD. YOSEMITE and RHINE and the extension study RHONE X measured the safety and efficacy of faricimab for the treatment of DME.1

Extension studies AVONELLE X and RHONE X are still underway to determine the long-term safety and efficacy of wet AMD and DM), respectively. RHONE X is expected to conclude in August 2023, and AVONELLE X is expected to conclude in August 2024.2,3

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. The study is expected to conclude in fall 2023.4

TENAYA and LUCERNE trials

The results of the phase III TENAYA and LUCERNE trials showed that faricimab (Hoffman-La Roche) INTERESTING-2 DIFFERENT MANUFACTURERS? 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 AMD, according to Robyn Guymer, ADD DEGREE? 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 VEGF-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.

YOSEMITE and RHINE trials

The 1-year results of the ongoing 2-year YOSEMITE and RHINE trials showed favorable results for faricimab for treating DME. The visual gains achieved with every-16-week dosing were non-inferior to those of aflibercept (Eylea) 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, SC, presented the results at the Association for Research in Vision and Ophthalmology’s 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 after 6 initial every-4-week doses; faricimab 6.0 mg treated according to a personalized treatment interval (PTI) based on the treat-and-extend concept after 4 initial every-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 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 (ETDRS) Severity Scale ) from baseline, the proportion of patients with a 15 or greater gain in ETDRS letters from baseline, the change in 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.

References
1. FDA accepts application for Roche's faricimab for the treatment of neovascular age-related macular degeneration (NAMD) and diabetic macular edema (DME). Roche. https://www.roche.com/investors/updates/inv-update-2021-07-29b.htm
2. A study to evaluate the long-term safety and tolerability of Faricimab in participants with neovascular age-related macular degeneration. https://clinicaltrials.gov/ct2/show/NCT04777201
3. A study to evaluate the long-term safety and tolerability of Faricimab in participants with diabetic macular edema. https://clinicaltrials.gov/ct2/show/NCT04432831
4. A study to evaluate the efficacy and safety of Faricimab in participants with macular edema secondary to branch retinal vein occlusion. https://clinicaltrials.gov/ct2/show/study/NCT04740905