The efficacy of Vumerity is based upon bioavailability studies in patients with relapsing forms of multiple sclerosis and healthy subjects comparing oral dimethyl fumarate delayed-release capsules to Vumerity delayed-release capsules (see full labeling).
The clinical studies described below were conducted using dimethyl fumarate.
The efficacy and safety of dimethyl fumarate were demonstrated in two studies (Studies 1 and 2) that evaluated dimethyl fumarate taken either twice or three times a day in patients with relapsing-remitting multiple sclerosis (RRMS).
Study 1: Placebo-Controlled Trial in RRMS
Study 1 was a 2-year randomized, double-blind, placebo-controlled study in 1234 patients with RRMS. The primary endpoint was the proportion of patients relapsed at 2 years. Additional endpoints at 2 years included the number of new or newly enlarging T2 hyperintense lesions, number of new T1 hypointense lesions, number of Gd+ lesions, annualized relapse rate (ARR), and time to confirmed disability progression. Confirmed disability progression was defined as at least a 1 point increase from baseline EDSS (1.5 point increase for patients with baseline EDSS of 0) sustained for 12 weeks. Patients were randomized to receive dimethyl fumarate 240 mg twice a day (n=410), dimethyl fumarate 240 mg three times a day (n=416), or placebo (n=408) for up to 2 years. The median age was 39 years, median time since diagnosis was 4 years, and median EDSS score at baseline was 2. The median time on study drug for all treatment arms was 96 weeks.
Results showed that treatment with dimethyl fumarate achieved a statistically significant effect on all of the endpoints described above and the 240 mg three times daily dose showed no additional benefit over the dimethyl fumarate 240 mg twice daily dose. The following results are for dimethyl fumarate 240 mg twice daily vs placebo, respectively:
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Proportion relapsing (primary endpoint): 27% vs 46% (relative risk reduction, 49%; P <.0001)
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ARR: 0.172 vs 0.364 (relative reduction, 53%; P <.0001)
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Proportion with disability progression: 16% vs 27% (relative risk reduction, 38%; P =.005)
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Mean number of new or newly enlarging T2 lesions over 2 years: 2.6 vs 17 (P <.0001)
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Percentage of patients with no new or newly enlarging lesions: 45% vs 27%
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Number of Gd+ lesions at 2 years: 0.1 vs 1.8 (relative odds reduction, 90%; P <.0001)
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Mean number of new T1 hypointense lesions over 2 years: 1.5 vs 5.6 (P <.0001)
Study 2: Placebo-Controlled Trial in RRMS
Study 2 was a 2-year multicenter, randomized, double-blind, placebo-controlled study that also included an open-label comparator arm in patients with RRMS. The primary endpoint was the annualized relapse rate at 2 years. Additional endpoints at 2 years included the number of new or newly enlarging T2 hyperintense lesions, number of T1 hypointense lesions, number of Gd+ lesions, proportion of patients relapsed, and time to confirmed disability progression as defined in Study 1. Patients were randomized to receive dimethyl fumarate 240 mg twice a day (n=359), dimethyl fumarate 240 mg three times a day (n=345), an open-label comparator (n=350), or placebo (n=363) for up to 2 years. The median age was 37 years, median time since diagnosis was 3 years, and median EDSS score at baseline was 2.5. The median time on study drug for all treatment arms was 96 weeks.
Results showed that treatment with dimethyl fumarate achieved a statistically significant effect on the relapse and MRI endpoints described above and the 240 mg three times daily dose showed no additional benefit over the dimethyl fumarate 240 mg twice daily dose. The following results are for dimethyl fumarate 240 mg twice daily vs placebo, respectively:
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ARR: 0.224 vs 0.401 (relative reduction, 44%; P <.0001)
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Proportion relapsing: 29% vs 41% (relative risk reduction, 34%; P =.002)
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Proportion with disability progression: 13% vs 17% (relative risk reduction, 21%; P =.25)
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Mean number of new or newly enlarging T2 lesions over 2 years: 5.1 vs 17.4 (P <.0001)
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Percentage of patients with no new or newly enlarging lesions: 27% vs 12%
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Number of Gd+ lesions at 2 years: 0.5 vs 2.0 (relative odds reduction, 74%; P <.0001)
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Mean number of new T1 hypointense lesions over 2 years: 3.0 vs 7.0 (P <.0001)