Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing–Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study

• DOI: 10.1007/s40120-024-00637-2
• Publication Date: 2024-06-27T11:02:25Z
• Authors: Barry A. Singer; Sibyl Wray; Mark Gudesblatt; Barbara Bumstead; Tjalf Ziemssen; Ashley Bonnell; Matthew Scaramozza; Seth Levin; Mathura Shanmugas...; Hailu Chen; Jason P. Mendoza; James B. Lewin; Sai L. Shankar
• Keywords: Dimethyl fumarate; Quartile; Relapsing remitting

In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different patients and without lymphopenia. EVOLVE-MS-1—an open-label, 96-week, phase 3 study—assessed DRF safety exploratory relapsing–remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) lymphopenia (≥ 1 below lower limit normal [LLN]) (all ALCs ≥ LLN); (2) across quartiles stratified week 96 baseline: Q1 47% decline); Q2 (30% < Q3 (12% 30% Q4 (< 12% decline). Baseline characteristics were between (n = 593) 452). At 96, adjusted annualized relapse rate (ARR; 95% confidence interval) 0.14 (0.11–0.17) 0.12 (0.09–0.15) Estimated proportions 12-week confirmed disability progression (CDP12) at 10.2% 9.3% When (Q1–Q4), ARR 0.11 (Q1), 0.09 (Q2), 0.13 (Q3), 0.17 (Q4). CDP12 9.6% 5.7% 10.9% no evidence disease activity achieved 47.2% 47.8% 45.4% 37.3% (Q4) patients. DRF-treated EVOLVE-MS-1, radiological measurements indicated reduced regardless or magnitude baseline; however, who had greater declines appeared have numerically higher free relapses gadolinium-enhancing lesions compared those smallest decline. supports prior that, while may contribute outcomes, it is the primary mechanism action. ClinicalTrials.gov identifier NCT02634307.