Diroximel Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Interim Safety and Efficacy Results from the Phase 3 Evolve-MS-1 Study

Background: Diroximel fumarate (DRF) is an oral fumarate for the treatment of relapsing multiple sclerosis (MS). DRF has better gastrointestinal (GI) tolerability and lower rates of discontinuation due to GI adverse events (AE) compared with dimethyl fumarate (DMF). Outcomes have not previously been reported for young adult patients with MS treated with DRF.

Objectives: To assess interim safety, GI tolerability, and efficacy of DRF in young adults (age 18–25 years) participating in the EVOLVE-MS-1 study (NCT02634307).

Methods: Patients entered the open-label, 96-week EVOLVE-MS-1 study either as newly diagnosed patients or after completing the randomized, double-blind, 5-week phase 3 EVOLVE-MS-2 study (NCT03093324) of DRF or DMF.

Results: As of September 2020, 1057 patients were enrolled in EVOLVE-MS-1, of which 65 patients were young adults, age 18–25 years (mean [standard deviation; SD] age, 22.6 [2.0] years; female, 61.5%). At baseline, mean (SD) time since diagnosis was 1.6 (2.0) years and mean (SD) Expanded Disability Status Scale score was 1.66 (1.10). Treatment-emergent AEs occurred in 59 (90.8%) patients; most common AEs were flushing (n=21, 32.3%), MS relapse (n=15, 23.1%), and nasopharyngitis (n=16, 24.6%). Serious AEs were reported in 10 (15.4%) patients; 1 (1.5%) death was reported and was deemed by the investigator not to be related to study treatment. GI AEs occurred in 40.0% of patients; no GI AEs led to treatment discontinuation. Mean absolute lymphocyte count (ALC) was 1.52 x 10⁹/L (n=56) at Week 48 versus 1.86 x 10⁹/L (n=65) at baseline, corresponding to an 18% reduction in ALC from baseline to Week 48. Annualized relapse rate (ARR) was 0.206 (95% CI 0.11–0.38) at 2 years, representing a 78.6% (95% CI 61.6–88.0; p < 0.0001) reduction from the 12 months before study entry (0.961 [95% CI 0.79–1.17]). At Week 48, the estimated proportion of patients who were relapse-free was 79.0% and the estimated proportion who had no evidence of disease activity (NEDA-3) was 54.7%. The percentage of patients who were Gd+ lesion-free at Week 48 was 73.2% compared with 46.2% at baseline.

Conclusions: Safety, GI tolerability, and efficacy in the young adult population of EVOLVE-MS-1 were consistent with the overall adult study population. Clinical and radiological (Gd+ lesion counts) outcomes significantly improved, and no discontinuations due to GI AEs were seen. These data suggest that DRF is an effective treatment option for young adults with MS. Data for ages 18–29 will also be assessed.

Study Support: Biogen