Chugai Pharmaceutical Submits New Drug Application in Japan for Faricimab, a Bispecific Antibody for DME and nAMD with Extended Dosing Interval and Efficacy Comparable to Aflibercept

Recently, Chugai Pharmaceutical Co., Ltd., a Roche subsidiary, announced that it has submitted a New Drug Application (NDA) for faricimab to the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD).

Diabetic macular edema (DME) is a complication of diabetic retinopathy (DR) that can lead to blindness in severe cases. DR is caused by damaged blood vessels and the formation of new blood vessels in the eye, resulting in the leakage of blood and fluid into the retina. This leads to swelling in certain areas of the retina and impaired blood supply. DME refers to the leakage of fluid from damaged vessels into the macula, causing swelling. The macula is the central region of the retina responsible for the sharp vision required for reading and driving. According to statistics, DME affects approximately 21 million people worldwide, and its incidence is expected to increase in the future as the prevalence of diabetes rises. Currently, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is the internationally recognized first-line treatment.

Neovascular age-related macular degeneration (nAMD), also known as wet age-related macular degeneration, is one of the major types of age-related macular degeneration (AMD). It accounts for 15% to 20% of all AMD patients, affects approximately 20 million people worldwide, and is a leading cause of blindness in individuals aged 60 years and older. AMD is a chronic, progressive disease that involves the macular retina and leads to central vision impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for nAMD; however, the visual benefits of anti-VEGF therapy gradually diminish with prolonged treatment.

Faricimab is a bispecific antibody specifically designed for ocular use, treating multiple retinal diseases by blocking the angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A) pathways. Ang-2 and VEGF-A disrupt vascular stability, leading to the formation of new leaky blood vessels and increased inflammatory responses, ultimately resulting in vision loss.

This New Drug Application is based on the YOSEMITE and RHINE studies conducted in patients with DME, as well as the TENAYA and LUCERNE studies conducted in patients with nAMD.

YOSEMITE and RHINE were two identical randomized, multicenter, double-blind, global Phase III studies enrolling a total of 1,891 patients with DME (940 in YOSEMITE and 951 in RHINE). In these studies, patients were randomized into three groups to receive either faricimab 6.0 mg with a personalized dosing interval of up to every 16 weeks (q16w), faricimab 6.0 mg every 8 weeks (q8w), or the control aflibercept 2.0 mg every 8 weeks (q8w).

In December 2020, Roche announced that the YOSEMITE and RHINE studies met their primary endpoints: compared with the aflibercept (q8w) group, both faricimab treatment groups demonstrated non-inferior visual acuity gains. Regarding secondary endpoints, in both studies, more than half of the patients in the faricimab individualized dosing group maintained a 16-week treatment interval during the first year.

TENAYA and LUCERNE are also two identical randomized, multicenter, double-blind, global Phase III studies that enrolled a total of 1,329 patients with nAMD (671 in TENAYA and 658 in LUCERNE). The primary endpoint of the studies was the best-corrected visual acuity (BCVA) score from baseline to Week 48. Both studies comprised two treatment arms: faricimab 6.0 mg (administered every 8, 12, or 16 weeks [q8w, q12w, or q16w] based on disease activity assessments at Weeks 20 and 24) and aflibercept 2.0 mg administered every 8 weeks (q8w).

In January 2021, Roche announced that the TENAYA and LUCERNE studies met their primary endpoints. The visual acuity outcomes for patients receiving faricimab injections every 16 weeks were non-inferior to those receiving aflibercept injections every 8 weeks. During the first year, nearly half (45%) of patients in both studies received faricimab treatment every 16 weeks.

In terms of safety, faricimab was well tolerated in the aforementioned four studies, with no new safety signals identified.

As the first bispecific antibody targeting ocular diseases to be submitted for marketing approval, faricimab is expected to secure a foothold in the ophthalmology field in the future, driven by its superior efficacy and extended dosing intervals.

Anti-VEGF drugs are currently the first-line treatment for fundus vascular diseases such as DME and nAMD. Currently approved ophthalmic anti-VEGF agents include aflibercept, conbercept, ranibizumab, and brolucizumab, among which aflibercept and conbercept are fusion proteins, while ranibizumab and brolucizumab are monospecific antibodies.

In addition to the aforementioned faricimab, a dual-target ophthalmic drug, RemeGen and Innovent Biologics in China have also developed dual-target therapeutics for ophthalmic diseases, RC28-E and IBI-302, respectively. RC28-E is a VEGF/fibroblast growth factor (FGF) dual-target fusion protein that effectively inhibits neovascularization and slows disease progression by blocking VEGF and angiogenic factors within the FGF family. Currently, RC28-E is undergoing a multicenter, randomized, active-controlled Phase II exploratory clinical trial in China for the treatment of DME. IBI-302 is a dual-target specific recombinant fully human fusion protein that simultaneously inhibits VEGF-mediated neovascularization and the complement activation pathway. In April this year, the first patient was dosed in its Phase II study for the treatment of nAMD.