Roche's Faricimab Demonstrates Non-Inferior Efficacy to Eylea with Extended Dosing Intervals up to Every Four Months in Phase III Trials for DME and nAMD

February 16, 2021 /Bio ValleyBIOON/ -- Roche recently announced the evaluation of the bispecific antibody faricimab for the treatment ofDiabetesDetailed Results from Four Global Phase 3 Studies in Diabetic Macular Edema (DME) and Neovascular or “Wet” Age-Related Macular Degeneration (nAMD). These studies consistently demonstrated that the every-4-month dosing regimen of faricimab was non-inferior to the every-2-month dosing regimen of Eylea (aflibercept) in terms of visual acuity gains. During the first year of the two DME studies (YOSEMITE and RHINE) and the two nAMD studies (TENAYA and LUCERNE), approximately half of the patients eligible for extended faricimab dosing were able to receive treatment every 4 months.Faricimab is the first intravitreal ophthalmic drug to achieve this dosing interval (once every 4 months) in Phase 3 studies for the treatment of DME and nAMD.Furthermore, during the first year, approximately three-quarters of patients eligible for extended faricimab dosing were able to receive treatment every 3 months or longer. Across all four studies, faricimab was generally well tolerated, with no new or unexpected safety signals identified.

Detailed results from four Phase 3 studies were presented at the 18th Annual Angiogenesis, Exudation, and Degeneration (AED) Meeting held on February 13, 2021.. The results of all four studies will be submitted to regulatory authorities worldwide, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), to consider regulatory approval of faricimab for the treatment of DME and nAMD.

Dr. Jeffrey Heier, Director of Retina Research at the Boston Eye Consultants, stated, “These faricimab study data provide a new treatment option for two common causes of blindness: diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). The potential of faricimab to extend treatment intervals may help patients who struggle to keep up with regular doctor visits and intravitreal injections required to maintain vision.”

Faricimab Structure (Image Source: cahiers-ophtalmologie.fr)

Although anti-vascular endothelial growth factor (VEGF) monotherapy injections significantly reduce vision loss in patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD), the treatment burden associated with frequent intravitreal injections and physician visits may lead to undertreatment and potentially suboptimal visual outcomes.

Faricimab is the first bispecific antibody specifically designed for the eye. Unlike current treatments for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) that inhibit the VEGF pathway, faricimab targets two distinct pathways—angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A)—both of which drive various retinal diseases, including nAMD and DME. Ang-2 and VEGF-A contribute to vision loss by disrupting vascular stability, promoting the formation of new leaky blood vessels, and increasing inflammatory responses. By simultaneously blocking these two pathways, faricimab aims to stabilize blood vessels and reduce inflammation and leakage more effectively than inhibiting either pathway alone. This approach may improve visual outcomes more significantly than anti-VEGF monotherapy, thereby reducing the frequency of required intravitreal injections.

Levi Garraway, M.D., Chief Medical Officer and Global Head of Product Development at Roche, stated, “These positive results demonstrate thatFaricimab has the potential to become the first treatment for neovascular age-related macular degeneration (nAMD) in 15 years, and the first in nearly 10 yearsDiabetesNovel Drugs for Diabetic Macular Edema (DME).“This is an exciting time for our ophthalmology clinical development program, with multiple Phase 3 successes achieved by two drugs in our late-stage pipeline. We aim to bring these potential treatments to patients with retinal diseases as soon as possible.”

Diabetic Macular Edema - DME (Image source: bceye.com)

YOSEMITE and RHINE are two global Phase 3 studies with identical designs, inDiabetesThe study was conducted in patients with diabetic macular edema (DME) to evaluate two dosing regimens of faricimab (administered every 2 months, or personalized treatment intervals [PTI] of up to every 4 months) and compare them with the every-2-months dosing regimen of Eylea. Patients in the PTI group received faricimab every 1, 2, 3, or 4 months, with adjustments made based on their disease activity.

Both studies met their primary endpoints: faricimab consistently demonstrated non-inferiority to Eylea in terms of visual acuity improvement. In the YOSEMITE study, the mean gain in visual acuity was +11.6 and +10.7 ETDRS letters in the faricimab PTI and every-2-months groups, respectively, compared with +10.9 letters in the Eylea group. In the RHINE study, the mean gain in visual acuity was +10.8 and +11.8 ETDRS letters in the faricimab PTI and every-2-months groups, respectively, compared with +10.3 letters in the Eylea group.

The secondary endpoints of these two studies were to measure the proportion of patients in the faricimab PTI group who achieved a dosing interval of every 3 months or every 4 months by the end of the first year. Notably, in the YOSEMITE study, 52.8% (n=151/286) of patients in the faricimab PTI group, and in the RHINE study, 51% (n=157/308) of patients in the faricimab PTI group, achieved a every-4-month dosing schedule within the first year. Additionally, 21% (n=60/286) of patients in the YOSEMITE study and 20.1% (n=62/308) of patients in the RHINE study in the faricimab PTI group achieved a every-3-month dosing schedule. Combined, more than 70% of patients in the faricimab PTI group were able to maintain an interval of 3 months or longer between treatments by the end of the first year. In both studies, faricimab administered every 4 months demonstrated a greater reduction in central subfield thickness (CST) compared with Eylea administered every 2 months.

Neovascular Age-Related Macular Degeneration (nAMD, Image source: researchgate.net)

TENAYA and LUCERNE are two identical, global Phase 3 studies conducted in patients with neovascular age-related macular degeneration (nAMD) to evaluate faricimab dosing regimens administered every 2, 3, or 4 months (based on disease activity assessments at Weeks 20 and 24), compared with Eylea administered every 2 months.

Both studies met their primary endpoints: faricimab consistently demonstrated non-inferiority to Eylea in terms of visual acuity improvement. In the TENAYA and LUCERNE studies, the mean increase in visual acuity from baseline in the faricimab groups was +5.8 and +6.6 letters, respectively, compared with +5.1 and +6.6 letters in the Eylea groups, respectively.

Two studies also measured the proportion of patients receiving faricimab every 3 or 4 months during the first year. Importantly, 45.7% (n=144/315) of patients in the TENAYA study and 44.9% (n=142/316) in the LUCERNE study were able to receive faricimab every 4 months during the first year. Additionally, 34% (n=107/315) of patients in the TENAYA study and 32.9% (n=104/316) in the LUCERNE study were able to receive faricimab every 3 months. Combined, nearly 80% of patients in the faricimab treatment group maintained a dosing interval of 3 months or longer during the first year. In both studies, faricimab administered every 4 months demonstrated a greater reduction in central subfield thickness (CST) compared with Eylea administered every 2 months. (Bioon.com)

Original Source: New phase III data show Roche’s faricimab is the first investigational injectable eye medicine to extend time between treatments up to four months in two leading causes of vision loss, potentially reducing treatment burden for patients