Studies Show Faricimab Improved and Maintained Vision in Wet AMD and DME, Extending Time Between Treatments to 4 Months

Genentech announced The Lancet has published two papers highlighting 1-year results from four pivotal phase 3 studies of faricimab, an investigational bispecific antibody, in wet age related macular degeneration (AMD) and diabetic macular edema (DME). 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 4 months achieved noninferior vision gains compared to aflibercept, given every 2 months. Notably, about half of eligible faricimab patients were able to go 4 months between treatments in the first year, and approximately three-quarters could go 3 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 4 months,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, said in a company news release. “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, 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

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 3 or 4 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 4 months in the first year. An additional 34% (n=107/315) of patients in TENAYA and 33% (n=104/316) in LUCERNE were able to be treated every 3 months. Combined, nearly 80% of faricimab-treated patients were able to go 3 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. 

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In the YOSEMITE and RHINE studies in DME, the average vision gains from baseline at 1 year were +11.6 and +10.8 eye chart letters in the faricimab treat[1]and-extend arms, +10.7 and +11.8 letters in the 2-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 3 or 4 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 4-month dosing at 1 year. An additional 21% (n=60/286) of faricimab treat-and-extend patients in YOSEMITE and 20% (n=62/308) in RHINE achieved 3-month dosing. Combined, more than 70% of faricimab treat-and-extend patients were able to go 3 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. 

Faricimab is currently under review by the FDA for the treatment of wet AMD and DME. The European Medicines Agency is also currently evaluating the faricimab Marketing Authorization Application for the treatment of wet AMD and 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 Saturday, February 12.

About the TENAYA and LUCERNE Studies

TENAYA (NCT03823287) and LUCERNE (NCT03823300) are two identical, randomized, multicenter, double-masked, global phase 3 studies evaluating the efficacy and safety of faricimab compared to aflibercept in 1,329 people living with wet AMD (671 in TENAYA and 658 in LUCERNE). The studies each have two treatment arms: faricimab 6.0 mg administered at fixed intervals of 2, 3, or 4 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 2-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 from baseline, averaged over weeks 40, 44 and 48. Secondary endpoints include: safety; the percentage of participants in the faricimab arm receiving treatment every 2, 3 and 4 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 

YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical, randomized, multicenter, double-masked, global phase 3 studies evaluating the efficacy and safety of faricimab compared to aflibercept in 1,891 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 4 months using a treat[1]and-extend approach after four initial monthly doses; faricimab 6.0 mg administered at fixed 2-month intervals after six initial monthly doses; and aflibercept administered at fixed 2-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. 

The primary endpoint of the studies is the average change in BCVA score from baseline at 1 year, averaged over weeks 48, 52 and 56. Secondary endpoints included: safety; the percentage of participants in the treat[1]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.