General Information

Vabysmo (faricimab-svoa) is a vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) inhibitor.

Vabysmo is specifically indicated for the treatment of patients with Neovascular (wet) Age-Related Macular Degeneration (nAMD) and Diabetic Macular Edema.

Vabysmo (faricimab-svoa) is supplied as a solution for intravitreal injection. Each vial should only be used for the treatment of a single eye.

Neovascular (wet) Age-Related Macular Degeneration (nAMD)

• The recommended dose for Vabysmo is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for the first 4 doses, followed by optical coherence tomography and visual acuity evaluations 8 and 12 weeks later to inform whether to give a 6 mg dose via intravitreal injection on one of the following three regimens: 1) Weeks 28 and 44; 2) Weeks 24, 36 and 48; or 3) Weeks 20, 28, 36 and 44. Although additional efficacy was not demonstrated in most patients when Vabysmo was dosed every 4 weeks compared to every 8 weeks, some patients may need every 4 week (monthly) dosing after the first 4 doses. Patients should be assessed regularly.

Diabetic Macular Edema (DME)

• Vabysmo is recommended to be dosed by following one of these two dose regimens: 1) 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days ± 7 days, monthly) for at least 4 doses. If after at least 4 doses, resolution of edema based on the central subfield thickness (CST) of the macula as measured by optical coherence tomography is achieved, then the interval of dosing may be modified by extensions of up to 4 week interval increments or reductions of up to 8 week interval increments based on CST and visual acuity evaluations through week 52; or 2) 6 mg dose of Vabysmo can be administered every 4 weeks for the first 6 doses, followed by 6 mg dose via intravitreal injection at intervals of every 8 weeks (2 months) over the next 28 weeks. Although additional efficacy was not demonstrated in most patients when Vabysmo was dosed every 4 weeks compared to every 8 weeks, some patients may need every 4 week (monthly) dosing after the first 4 doses. Patients should be assessed regularly.

Mechanism of Action

Vabysmo (faricimab-svoa) is a humanized bispecific antibody that acts through inhibition of two pathways by binding to VEGF-A and Ang-2. By inhibiting VEGF-A, faricimab suppresses endothelial cell proliferation, neovascularization and vascular permeability. By inhibiting Ang-2, faricimab is thought to promote vascular stability and desensitize blood vessels to the effects of VEGF-A. Ang-2 levels are increased in some patients with nAMD and DME. The contribution of Ang-2 inhibition to the treatment effect and clinical response for nAMD and DME has yet to be established.

Side Effects

The most common adverse effect associated with the use of Vabysmo was conjunctival hemorrhage.

Endophthalmitis and retinal detachments may occur following intravitreal injections. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management. Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. There is a potential risk of arterial thromboembolic events (ATEs) associated with VEGF inhibition.

Clinical Trial Results

The FDA approval was based on positive results across four Phase 3 studies in wet AMD and DME: TENAYA and LUCERNE in patients with wet AMD and YOSEMITE and RHINE in patients with DME.

TENAYA and LUCERNE are two identical, randomized, multicenter, double-masked, global studies evaluating the efficacy and safety of Vabysmo compared to aflibercept in 1,329 people living with wet age-related macular degeneration (671 in TENAYA and 658 in LUCERNE). Both studies met their primary endpoint, with Vabysmo given at intervals of up to every four months consistently shown to offer visual acuity gains that were non-inferior to aflibercept given every two months. In TENAYA and LUCERNE, the average vision gains from baseline at one year in the Vabysmo arms were +5.8 and +6.6 letters, respectively, compared to +5.1 and +6.6 letters in the aflibercept arms.  

YOSEMITE and RHINE are two identical, randomized, multicenter, double-masked, global studies evaluating the efficacy and safety of Vabysmo compared to aflibercept in 1,891 people with diabetic macular edema (940 in YOSEMITE and 951 in RHINE).  Both studies met their primary endpoint, with Vabysmo at intervals of up to every four months consistently shown to offer visual acuity gains that were non-inferior to aflibercept given every two months. In YOSEMITE, the average vision gains from baseline at one year were +11.6 and +10.7 eye chart letters in the Vabysmo treat-and-extend and two-month arms, respectively, and +10.9 letters in the aflibercept arm. In RHINE, the average vision gains from baseline at one year were +10.8 and +11.8 letters in the Vabysmo treat-and-extend and two-month arms, respectively, and +10.3 letters in the aflibercept arm.