Roche announced that the US Food and Drug Administration (FDA) has approved Vabysmo (faricimab-svoa) for the treatment of neovascular or “wet” age-related macular degeneration (nAMD) and diabetic macular edema (DME). Neovascular AMD and DME are two leading causes of vision loss worldwide.
Vabysmo targets and inhibits two disease pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A).
Vabysmo is the first and only FDA-approved injectable eye medicine for nAMD and DME that improves and maintains vision with treatments from one to four months apart in the first year following four initial monthly doses, based on evaluation of the patient’s anatomy and vision outcomes. Standard of care for nAMD and DME typically requires eye injections every one to two months.
“Vabysmo represents an important step forward for ophthalmology. It is the first bispecific antibody approved for the eye and a major advance in treating retinal conditions such as neovascular AMD and diabetic macular edema,” said Charles Wykoff, M.D., Ph.D., director of research at retina consultants of Texas in Houston and a Vabysmo phase III investigator. “With Vabysmo, we now have the opportunity to offer patients a medicine that could improve their vision, potentially lowering treatment burden with fewer injections over time.”
The approval is based on positive results across four phase III studies in nAMD and DME. The studies consistently showed that patients treated with Vabysmo given at intervals of up to four months achieved non-inferior vision gains versus aflibercept given every two months in the first year. Vabysmo was generally well tolerated in all four studies, with a favourable benefit-risk profile. The most common adverse reaction (=5%) reported in patients receiving Vabysmo was conjunctival haemorrhage (7%). Two scientific papers and an editorial on these one-year results were recently published in The Lancet.
Vabysmo is designed to block pathways involving Ang-2 and VEGF-A. Ang-2 and VEGF-A are thought to contribute to vision loss by destabilising blood vessels, which may cause new leaky blood vessels to form and increase inflammation. While additional research continues, inhibition of both pathways has been shown in preclinical studies to have potentially complementary benefits, stabilising vessels, and thereby reducing vessel leakage and inflammation.
“Vabysmo provides a new approach to treating vision-threatening retinal conditions through a mechanism of action that targets two pathways simultaneously,” said Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development. “This is our second FDA approval in ophthalmology in recent months, underscoring our commitment to people living with retinal conditions.”
With Vabysmo, people with nAMD initially receive four monthly treatments. Based on anatomical and vision outcomes, they may receive subsequent treatments every two, three or four months. People with DME are initially given four monthly treatments. Subsequently, their treatment may be extended or reduced based on anatomical and vision outcomes, with a range of one to four months between doses. A second approved treatment regimen for DME involves six monthly loading doses, followed by treatment every two months. Some people with nAMD and DME may be treated monthly if needed, although additional efficacy was not demonstrated in most people given Vabysmo every month.
Roche has ongoing long-term extension studies for Vabysmo in people with nAMD and DME. These include AVONELLE-X, an extension study of TENAYA and LUCERNE evaluating the long-term safety and tolerability of Vabysmo in nAMD, and RHONE-X, an extension study of YOSEMITE and RHINE evaluating the long-term safety and tolerability of Vabysmo in DME. Additionally, the COMINO and BALATON trials are also underway, evaluating the efficacy and safety of Vabysmo in people with macular edema following retinal vein occlusion.
Vabysmo will be available in the United States in the coming weeks. The European Medicines Agency is also currently evaluating the Vabysmo Marketing Authorisation Application for the treatment of nAMD and DME.
TENAYA (NCT03823287) and LUCERNE (NCT03823300) are two identical, randomised, multicentre, double-masked, global phase III studies evaluating the efficacy and safety of Vabysmo compared to aflibercept in 1,329 people living with neovascular or “wet” age-related macular degeneration (671 in TENAYA and 658 in LUCERNE). The studies each have two treatment arms: Vabysmo 6.0 mg administered at intervals of two, three, or four months, following four initial monthly doses, selected based on objective assessment of disease activity at weeks 20 and 24; and aflibercept 2.0 mg administered at fixed two-month intervals after three initial monthly doses. 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 averaged over weeks 40, 44 and 48. Secondary endpoints include: safety; the percentage of participants in the Vabysmo 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; change in central subfield thickness (CST) from baseline over time; and change in total area of choroidal neovascularisation (CNV) lesion and leakage from baseline over time.
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.
The studies also measured the proportion of people in the Vabysmo arm that were treated on dosing schedules of every three or four months during the first year. In both studies, comparable reductions in CST and CNV size and area of leakage were observed with Vabysmo given at intervals of up to four months versus aflibercept given every two months in the first year. Vabysmo was generally well-tolerated in both studies, with a favourable benefit-risk profile. In TENAYA and LUCERNE, the most common adverse reactions (=3% of patients) included conjunctival haemorrhage, vitreous floaters, retinal pigment epithelial tears, increase of intraocular pressure and eye pain. Safety results were consistent across study arms.
YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical, randomised, multicentre, double-masked, global phase III 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). The studies each have three treatment arms: Vabysmo 6.0 mg administered up to every four months after four initial monthly doses using a treat-and-extend approach; Vabysmo 6.0 mg administered at two-month intervals after six initial monthly doses; and aflibercept administered at fixed two-month intervals after five initial monthly doses. 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, averaged over weeks 48, 52 and 56. Secondary endpoints included: safety; the percentage of participants in the treat-and-extend arm receiving Vabysmo 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; change in central subfield thickness (CST) from baseline over time; and percentage of patients with absence of intraretinal fluid over time.
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 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.
A secondary endpoint in both studies measured the proportion of people in the Vabysmo treat-and-extend arm that achieved dosing schedules of every three or four months at the end of the first year. In both studies, greater reductions in CST and intraretinal fluid were observed with Vabysmo given at intervals of up to four months versus aflibercept given every two months in the first year. Vabysmo was generally well-tolerated in both studies, with a favourable benefit-risk profile. In YOSEMITE and RHINE, the most common adverse reactions (=3% of patients) included conjunctival haemorrhage, vitreous floaters and increase of intraocular pressure.3 Safety results were consistent across study arms.
Vabysmo (faricimab-svoa) is the first bispecific antibody approved for the eye. It targets and inhibits two disease pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A contribute to vision loss by destabilising blood vessels, causing new leaky blood vessels to form and increasing inflammation. By blocking pathways involving Ang-2 and VEGF-A, Vabysmo is designed to stabilise blood vessels.
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