Assessments and Analysis Populations

Lymphopenia efficacy correlation in the overall DRF patient population in EVOLVE-MS-1 was assessed. Final safety and exploratory efficacy outcomes (clinical and radiological) were evaluated in a subset of patients with ALC values recorded at baseline and week 96. ALCs were collected at each visit (every 4 weeks). Patients were divided into two subgroups. In the first subgroup analysis, efficacy-related outcomes (adjusted annualized relapse rate [ARR], Expanded Disability Status Scale [EDSS], and gadolinium-enhancing [Gd+] lesion reductions) at 2 years in patients treated with DRF were compared between patients with lymphopenia (≥ 1 ALC test below the lower limit of normal [LLN] at any time during the study) or without lymphopenia (all ALCs remained at or greater than the LLN, defined as ALC = 0.91 × 10⁹/L). No patients developed severe, prolonged lymphopenia (< 0.5 × 10⁹/L for ≥ 6 months), as any patients who developed severe lymphopenia (ALC < 0.5 × 10⁹/L) for ≥ 4 weeks had DRF withdrawn, according to the EVOLVE-MS-1 protocol-defined stopping rule.

In the second subgroup analysis, patients were stratified into quartiles based on the decline in ALC from baseline to week 96. The four quartiles were Q1 (≥ 47% ALC decline from baseline); Q2 (30% to < 47% ALC decline from baseline); Q3 (12% to < 30% ALC decline from baseline); and Q4 (< 12% ALC decline from baseline). Change from baseline to week 96 in adjusted ARR, EDSS, Gd+ lesion reductions, zero relapses, and no evidence of disease activity-3 [NEDA-3] was reported for these quartiles.