Studies: Faricimab improved and maintained vision for patients with wet AMD, DME

Genentech announced on Monday a pair of papers published recently offer highlights of 1-year results from 4 pivotal Phase III studies of faricimab, an investigational bispecific antibody, in wet, or neovascular, age related macular degeneration (AMD) and diabetic macular edema (DME).

The company is currently awaiting FDA approval of faricimab for the treatment of wet AMD and DME. The papers were currently published in The Lancet, according to the company.

According to the company, all four studies – which enrolled more than 3,000 people in total – met their primary endpoints, showing that patients treated with faricimab up to every four months achieved non-inferior vision gains compared to aflibercept, given every two months. Notably, about half of eligible faricimab patients were able to go four months between treatments in the first year, and approximately three-quarters could go three months or longer in the TENAYA and LUCERNE wet AMD studies and the YOSEMITE and RHINE DME studies.

The current standard of care for these potentially blinding conditions requires eye injections as often as once a month.

“These data published in The Lancet reinforce the potential of faricimab as an important treatment option that may help improve and maintain vision while extending the time between treatments up to four months,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech. “We remain deeply committed to developing new medicines such as faricimab that may help preserve sight in many people living with serious retinal conditions.” 

If approved by the FDA, faricimab would be the first bispecific antibody for the eye, targeting and inhibiting two distinct pathways linked to a number of vision-threatening retinal conditions by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Inhibition of both pathways has been shown to have complementary benefits, stabilizing vessels and thereby reducing vessel leakage and inflammation more than inhibition of the VEGF-A pathway alone.

Key Findings

According to the company, in the TENAYA and LUCERNE studies in wet AMD, the average vision gains from baseline at one year in the faricimab arms were +5.8 and +6.6 letters, respectively, compared to +5.1 and +6.6 letters in the aflibercept arms. The studies also measured the proportion of people in the faricimab arm that were treated on dosing schedules of every three or four months during the first year. Importantly, 46% (n=144/315) of patients in TENAYA and 45% (n=142/316) in LUCERNE were able to be treated every four months in the first year.

The company noted that an additional 34% (n=107/315) of patients in TENAYA and 33% (n=104/316) in LUCERNE were able to be treated every three months. Combined, nearly 80% of faricimab-treated patients were able to go three months or longer between treatments during the first year. Consistent with vision outcomes, faricimab treatment resulted in a meaningful and comparable reduction in central subfield thickness (CST) and comparable decreases in choroidal neovascularization lesion size and area. Faricimab was generally well-tolerated in both studies, with a favorable benefit-risk profile. Ocular adverse events (AEs) were comparable across treatment arms and consistent with those expected with intravitreal anti-VEGF injections in patients with wet AMD.

In the YOSEMITE and RHINE studies in DME, the average vision gains from baseline at one year were +11.6 and +10.8 eye chart letters in the faricimab treat-and-extend arms, +10.7 and +11.8 letters in the two-month arms, and +10.9 and +10.3 letters in the aflibercept arms, respectively. A secondary endpoint in both studies measured the proportion of people in the faricimab treat-and-extend arms that achieved dosing schedules of every three or four months at the end of the first year. Importantly, 53% (n=151/286) of faricimab treat-and-extend patients in YOSEMITE and 51% (n = 157/308) in RHINE achieved four-month dosing at one year.

An additional 21% (n = 60/286) of faricimab treat-and-extend patients in YOSEMITE and 20% (n=62/308) in RHINE achieved three-month dosing. Combined, more than 70% of faricimab treat-and-extend patients were able to go three months or longer between treatments at the end of the first year. Reductions in CST and resolution of intraretinal fluid through the first year consistently favored faricimab over aflibercept. Faricimab was generally well-tolerated in both studies, with a favorable benefit-risk profile. Ocular AEs were comparable across treatment arms and consistent with those expected with intravitreal anti-VEGF injections in patients with DME.

Additionally, the COMINO and BALATON trials are underway, evaluating the efficacy and safety of faricimab in people with macular edema following retinal vein occlusion.

Two-year results for faricimab in DME will be presented at the Angiogenesis, Exudation, and Degeneration 2022 meeting, on Feb. 12.

About the TENAYA and LUCERNE Studies

The company noted that TENAYA (NCT03823287) and LUCERNE (NCT03823300) are two identical, randomly assigned, multicenter, double-masked, global Phase III studies evaluating the efficacy and safety of faricimab compared to aflibercept in 1329 people living with wet age-related macular degeneration (671 in TENAYA and 658 in LUCERNE). The studies each have two treatment arms: faricimab 6.0 mg administered at fixed intervals of two, three, or four months, following four initial monthly doses, selected based on objective assessment of disease activity at weeks 20 and 24; and aflibercept 2.0 mg administered at fixed two-month intervals. In both arms, sham injections were administered at study visits when treatment injections were not scheduled, to maintain the masking of investigators and participants.

The primary endpoint of the studies is the average change in best-corrected visual acuity (BCVA) score (the best distance vision a person can achieve – including with correction such as glasses – when reading letters on an eye chart) from baseline, averaged over weeks 40, 44 and 48. Secondary endpoints include: safety; the percentage of participants in the faricimab arm receiving treatment every two, three and four months; the percentage of participants achieving a gain, and the percentage avoiding a loss, of 15 letters or more in BCVA from baseline over time; change in central subfield thickness from baseline over time; and change in total area of choroidal neovascularization lesion and leakage from baseline over time.

About the YOSEMITE and RHINE Studies

The company noted that the YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical, randomly assigned, multicenter, double-masked, global Phase III studies evaluating the efficacy and safety of faricimab compared to aflibercept in 1891 people with diabetic macular edema (940 in YOSEMITE and 951 in RHINE). The studies each have three treatment arms: faricimab 6.0 mg administered up to every four months using a treat-and-extend approach after four initial monthly doses; faricimab 6.0 mg administered at fixed two-month intervals after six initial monthly doses; and aflibercept administered at fixed two-month intervals after five initial monthly doses. In all three arms, sham injections were administered at study visits when treatment injections were not scheduled, to maintain the masking of investigators and participants.

According to the company, the primary endpoint of the studies is the average change in best-corrected visual acuity (BCVA) score from baseline at one year, averaged over weeks 48, 52 and 56. Secondary endpoints included: safety; the percentage of participants in the treat-and-extend arm receiving faricimab every 1, 2, 3 and 4 months, at week 52; the percentage of participants achieving a two-step or greater improvement from baseline in diabetic retinopathy severity at week 52; the percentage of participants achieving a gain, and the percentage avoiding a loss, of 15 letters or more in BCVA from baseline over time; change in central subfield thickness from baseline over time; and percentage of patients with absence of intraretinal fluid over time.

According to Genentech, the European Medicines Agency has also validated the faricimab Marketing Authorization Application for the treatment of wet AMD and DME.