Diroximel fumarate (DRF) is a novel oral fumarate approved in the United States for relapsing forms of multiple sclerosis (MS). DRF undergoes pre-systemic hydrolysis to monomethyl fumarate (MMF), the same pharmacologically active metabolite as dimethyl fumarate (DMF). DRF 462 mg and DMF 240 mg produce bioequivalent exposure of MMF and are expected to have similar efficacy and safety profiles. In DMF-treated patients, annual rates of brain volume loss over 6 years ranged from -0.19 to -0.37, approaching rates observed in healthy adults (-0.1% to -0.3%).
To report percent brain volume change (PBVC) and impact on disability in patients from EVOLVE-MS-1 who have received DRF treatment for up to 2 years.
EVOLVE-MS-1 (NCT02634307) is an ongoing, open-label, phase 3 study to assess the long-term safety, tolerability, and efficacy of DRF 462 mg over 96 weeks in adults with relapsing-remitting MS. Normalized brain volume was assessed at baseline and used to calculate PBVC at Weeks 48 and 96. Confirmed Disability progression (CDP) was measured using the Expanded Disability Status Scale (≥1.5-, ≥1.0-, or ≥0.5-point increase from a baseline score of 0, 1.0-5.5, or 6.0, respectively), with changes sustained for 12 weeks. Estimated proportion of patients with CDP was calculated by the Kaplan-Meier method. No evidence of disease activity (NEDA)-3 was defined as no relapses, no 12-week CDP, and no new/enlarging T2 or new gadolinium-enhancing lesions. This post hoc analysis was conducted in a subgroup of patients who had brain volume scan measurements at baseline, Week 48, and Week 96. The Week 48 and Week 96 visits occurred within an analysis window of ±12 weeks.
As of 2 July 2019, a total of 1051 patients were enrolled in EVOLVE-MS-1 and 365 patients were included in this analysis. Median (range) exposure was 96 (75-100) weeks. Mean (SD) PBVC was -0.36 (0.60) from baseline to Week 48 and -0.35 (0.55) from Week 48 to Week 96. Estimated proportion of patients who were free of CDP was 94.3% at Week 48 and 90.7% at Week 96. The proportion of patients with NEDA-3 at Week 48 and Week 96 was 44.7% (163/365) and 25.2% (91/361), respectively.
Interim findings from the ongoing EVOLVE-MS-1 study demonstrate that yearly PBVC in DRF-treated patients approached the rate observed in healthy adults and was consistent with previous studies of DMF. Most patients remained free of CDP at 2 years.
Supported by: Biogen