Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA), under Priority Review, for faricimab for the treatment of wet, or neovascular, age-related macular degeneration (AMD) and diabetic macular edema (DME). The FDA has also accepted the company’s submission for diabetic retinopathy.

Faricimab will be the first and only bispecific antibody designed for the eye, if approved. It targets two distinct pathways – via angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A) – that drive a number of retinal conditions that can cause vision loss.

“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, M.D., Ph.D., chief medical officer and head of Global Product Development. “Therefore, we hope faricimab will become a new treatment option for millions of people living with wet AMD and DME.”

Wet AMD and DME are two leading causes of vision loss among adults in the United States. The BLA submission is based on positive results across four Phase III studies in wet AMD and DME. The studies consistently showed that faricimab, given at intervals of up to four months, offered non-inferior vision gains compared with aflibercept, given every two months. Approximately half of people eligible for extended dosing with faricimab were able to be treated every four months in the first year in the TENAYA and LUCERNE studies in wet AMD and the YOSEMITE and RHINE studies in DME. Faricimab is the first injectable eye medicine to achieve this length of time between treatments in Phase III studies for wet AMD and DME. Furthermore, approximately three-quarters of people eligible for extended dosing with faricimab were able to be treated every three months or longer in the first year. Faricimab was generally well-tolerated in all four studies, with no new or unexpected safety signals identified.

Genentech also has long-term extension studies underway for faricimab. These include AVONELLE X, an extension study of TENAYA and LUCERNE evaluating the long-term safety and efficacy of faricimab in wet AMD, and RHONE X, an extension study of YOSEMITE and RHINE evaluating the long-term safety and efficacy of faricimab in DME. Additionally, the COMINO and BALATON trials are also underway, evaluating the efficacy and safety of faricimab in people with macular edema secondary to two types of retinal vein occlusion (RVO): central RVO and branch RVO.

The European Medicines Agency has also validated the faricimab Marketing Authorization Application for the treatment of wet AMD and DME.

About the TENAYA and LUCERNE Studies

TENAYA (NCT03823287) and LUCERNE ( NCT03823300) are two identical, randomized, multicenter, double-masked, global Phase III studies evaluating the efficacy and safety of faricimab compared to aflibercept in 1,329 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 every two, three, or four months, 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 through week 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; and change in central subfield thickness (CST) from baseline over time.

Both studies met their primary endpoint, with faricimab consistently shown to offer non-inferior visual acuity gains to aflibercept. In TENAYA and LUCERNE, the average vision gains from baseline 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. 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. In both studies, faricimab given at intervals of up to four months offered reductions in CST comparable to aflibercept given every two months. Faricimab was generally well-tolerated in both studies, with no new or unexpected safety signals identified.

About the YOSEMITE and RHINE Studies

YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical, randomized, multicenter, double-masked, global Phase III 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 at personalized treatment intervals (PTI) of up to four months; faricimab 6.0 mg administered at fixed two-month intervals; and aflibercept 2.0 mg administered at fixed two-month intervals. 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 one year. Secondary endpoints include: safety; the percentage of participants in the personalized dosing arm receiving treatment every one, two, three and four 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 and change in central subfield thickness (CST) from baseline over time.

Both studies met their primary endpoint with faricimab consistently shown to offer non-inferior visual acuity gains to aflibercept. In YOSEMITE, the average vision gains from baseline were +11.6 and +10.7 eye chart letters in the faricimab PTI and two-month arms, respectively, and +10.9 letters in the aflibercept arm. In RHINE, the average vision gains from baseline were +10.8 and +11.8 letters in the faricimab PTI and two-month arms, respectively, and +10.3 letters in the aflibercept arm.

A secondary endpoint in both studies measured the proportion of people in the faricimab PTI arm that achieved dosing schedules of every three or four months at the end of the first year. Importantly, 53% (n=151/286) of faricimab PTI 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 PTI patients in YOSEMITE and 20% (n=62/308) in RHINE achieved three-month dosing. Combined, more than 70% of faricimab PTI patients were able to go three months or longer between treatments at the end of the first year. In both studies, faricimab given at intervals of up to four months demonstrated greater reductions in CST compared to aflibercept given every two months. Faricimab was generally well-tolerated in both studies, with no new or unexpected safety signals identified.

About Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a condition that affects the macula, the part of the eye that provides sharp, central vision needed for activities like reading, and is a leading cause of blindness for people aged 60 and over in the United States. Wet, or neovascular, AMD is an advanced form of the disease that can cause rapid and severe vision loss. Approximately 11 million people in the United States have some form of AMD, and of those, about 1.1 million have wet AMD.

Wet AMD is caused by growth of abnormal blood vessels, also referred to as choroidal neovascularization (CNV), into the macula. These vessels leak fluid and blood and cause scar tissue that destroys the central retina. This process results in a deterioration of sight over a period of months to years.

About Diabetic Macular Edema

Affecting approximately 750,000 people in the United States, diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy (DR). DR is the leading cause of blindness among adults aged 20 to 74 and affects nearly 7.7 million people in the United States. It occurs when damage to blood vessels and the formation of new blood vessels cause blood and/or fluid to leak into the retina – a part of the eye that sends information to the brain, enabling sight. This leads to swelling, as well as blockage of blood supply to some areas of the retina. DME occurs when the damaged blood vessels leak into and cause swelling in the macula – the central area of the retina responsible for the sharp vision needed for reading and driving. The number of people with DME is expected to grow as the prevalence of diabetes increases. The condition is associated with blindness when left untreated and decreased quality of life. There remains a significant unmet need for more effective, longer-lasting therapies for people with DME.

About faricimab

Faricimab is the first investigational bispecific antibody designed for the eye. It targets two distinct pathways – via angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A) – that drive a number of retinal conditions. Ang-2 and VEGF-A contribute to vision loss by destabilizing blood vessels, causing new leaky blood vessels to form and increasing inflammation. By simultaneously blocking both pathways involving Ang-2 and VEGF-A, faricimab is designed to stabilize blood vessels, potentially improving vision outcomes for longer for people living with retinal conditions.

About Genentech in Ophthalmology

Genentech is researching and developing new treatments for people living with a range of eye diseases that cause significant visual impairment and blindness, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), geographic atrophy (GA) and other retinal diseases. The company is also investigating platforms for sustained ocular drug delivery, including Port Delivery System with ranibizumab (PDS).

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California.