Roche's Faricimab Receives FDA Approval: First Bispecific Antibody for Retinal Diseases with Dosing Every 4 Months

Source: PharmaCube Info

Author: info

On January 28, Genentech, a member of the Roche Group, announced that the FDA had approved Vabysmo (faricimab-svoa) for the treatment of wet age-related macular degeneration (wAMD) and diabetic macular edema (DME).

Faricimab is a bispecific antibody that simultaneously targets two distinct signaling pathways: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2). Biologically, VEGF-A and Ang-2 signaling destabilize blood vessels, induce neovascularization, and promote inflammation. Faricimab effectively controls neovascularization by blocking the VEGF/VEGFR signaling pathway while also inhibiting Ang-2 signaling to improve vascular stability and reduce retinal inflammation.

Compared with单纯anti-VEGF therapy, Faricimab can reduce the frequency of ocular injections and improve long-term visual outcomes for patients when used to treat various retinal diseases. Currently, the dosing frequency of aflibercept (VEGFR-Fc fusion protein) can be administered once every 2 months (once a month for the first 3 months), making it the standard treatment for nAMD, with sales reaching $7.909 billion in 2020. Beovu (brolucizumab), developed by Novartis, is a single-chain antibody fragment (scFv) that allows for higher molar dosing and is the first anti-VEGF therapy for nAMD that requires only once every 3 months injection, with global sales of $190 million in 2020. The recently approved Faricimab from Roche is the first bispecific antibody approved for ophthalmic diseases and the first drug to achieve a 4-month dosing interval in Phase III studies for the treatment of DME and nAMD.

Age-related Macular Degeneration (AMD) is an eye disease that affects daily activities requiring clear central vision, such as reading. When it progresses to the advanced stage, it is referred to as neovascular age-related macular degeneration (nAMD), or wet age-related macular degeneration (wAMD). The pathology involves the uncontrolled growth of new and abnormal blood vessels beneath the macula, leading to swelling, bleeding, and/or fibrosis, which causes rapid and severe vision loss.

Neovascular Age-Related Macular Degeneration (nAMD)

Two Phase III studies, TENAYA (NCT03823287) and LUCERNE (NCT03823300), evaluated the efficacy and safety differences between faricimab and aflibercept in 671 and 658 nAMD patients, respectively.

The studies set two dosing groups: faricimab 6mg (once every 2, 3, or 4 months, determined by disease activity assessment at weeks 20 and 24) and aflibercept 2mg (once every 2 months). The primary endpoint of the studies was the mean change in best-corrected visual acuity (BCVA) score from baseline at week 48. Secondary endpoints included safety, the proportion of participants in the faricimab group receiving treatment once every 2, 3, or 4 months, the proportion of participants with an increase in BCVA score from baseline and avoiding a decrease of more than 15 letters, and the change in central macular thickness from baseline.

The results showed that faricimab was non-inferior to aflibercept in the improvement of visual acuity (BCVA score) from baseline at week 48 of treatment. In the TENAYA and LUCERNE studies, the improvements were 5.8 and 6.6 letters, respectively, compared to 5.1 and 6.6 letters in the aflibercept group, reaching the primary endpoint.

In the TENAYA study, 45.7% (144/315) of nAMD patients in the faricimab treatment group were able to achieve dosing every 4 months at year 1, while 34% (107/315) achieved dosing every 3 months; in the LUCERNE study, 44.9% (142/316) of patients in the faricimab treatment group achieved dosing every 4 months at year 1, while 32.9% (104/316) achieved dosing every 3 months. This means that nearly 80% of patients receiving faricimab treatment were able to achieve injection intervals of every 3 months or longer at 1 year. Additionally, faricimab administered every 4 months was non-inferior to aflibercept administered every 2 months in terms of reduction in central macular thickness.

DME is a complication of Diabetic Retinopathy (DR). In diabetic patients, excessively high blood sugar levels can damage blood vessels in the eye, causing blood and/or fluid to leak into the retina. This leads to the development of Diabetic Retinopathy (DR), characterized by swelling in certain areas of the retina and blockage of blood supply. If vascular damage and leakage occur in the central area of the retina, it results in Macular Edema, also known as Diabetic Macular Edema (DME). Without proper intervention and treatment, DME can severely threaten vision and impact quality of life. Currently, there are approximately 21 million DME patients globally, with around 750,000 in the United States. As the number of diabetic patients increases, the number of DME patients is also expected to rise, necessitating more effective and longer-lasting treatment options beyond anti-VEGF therapies.

Diabetic Macular Edema (DME)

For the DME indication, two Phase III studies, code-named YOSEMITE (NCT03622580) and RHINE (NCT03622593), evaluated the efficacy and safety differences between faricimab and aflibercept in 940 and 951 DME patients, respectively.

The study set up three dosing groups: faricimab 6mg (individualized dosing interval, up to 4 months, determined by disease severity), faricimab 6mg (once every 2 months), and aflibercept 2mg (once every 2 months). The primary endpoint was the mean change in Best Corrected Visual Acuity (BCVA) score from baseline at week 52. Secondary endpoints included safety, the proportion of participants in the faricimab individualized dosing interval group achieving dosing intervals of once every 1, 2, 3, or 4 months at week 52, the proportion of participants with a two-step or greater improvement in diabetic retinopathy severity from baseline at week 52, the proportion of participants with an increase in BCVA score from baseline and avoiding a decrease of 15 letters or more, and the change in central retinal thickness in the macular area from baseline.

The results showed that the improvement in visual acuity (BCVA score) of DME patients in the faricimab 6mg personalized dosing interval group and the faricimab 6mg every 2 months group was non-inferior to that of the aflibercept every 2 months group. In the YOSEMITE study, the mean increase in visual acuity from baseline was 11.6, 10.7, and 10.9 letters, respectively, for the three groups, while in the RHINE study, the mean increase was 10.8, 11.8, and 10.3 letters, respectively.

In the YOSEMITE study, 52.8% (151/286) of DME patients in the faricimab personalized dosing interval group achieved dosing every 4 months at Year 1, while 21% (60/286) achieved dosing every 3 months; in the RHINE study, 51% (157/308) of DME patients in the faricimab personalized dosing interval group achieved dosing every 4 months at Year 1, while 20.1% (62/308) achieved dosing every 3 months; this means that over 70% of DME patients receiving faricimab personalized interval dosing were able to achieve injection intervals of every 3 months or longer by the end of 1 year of treatment.

Faricimab will be the first innovative mechanism therapy for nAMD patients in 15 years and the first new therapy for DME patients in nearly 10 years.

Note: The original text has been abridged.