Background: Multiple sclerosis (MS) treatment involves disease-modifying therapies (DMTs) and symptom management. There is an unmet need for MS treatments that reverse demyelination and neuronal damage. Elezanumab (formerly ABT-555) is a monoclonal antibody that neutralizes repulsive guidance molecule A (RGMa), a neurite outgrowth inhibitor thought to be involved in MS.
Objective: Present the study design and baseline data from 2 studies investigating elezanumab efficacy and safety in patients with progressive MS (PMS) and relapsing MS (RMS).
Methods: RADIUS-R (NCT03737851) and RADIUS-P (NCT03737812) are 2 ongoing, 52-week, proof-of-concept, RAndomized, Double-blind, placebo-controlled, multIple-dose phase 2 stUdies investigating efficacy and safety of elezanumab added to Standard of care in patients with RMS and PMS, respectively. RADIUS-R includes patients with relapsing-remitting MS (RRMS; no relapse 6 months before screening), or active secondary-progressive MS (SPMS; relapse 6 to 24 months before screening). RADIUS-P includes patients with primary-progressive MS (PPMS) or non-active SPMS (no relapses 24 months before screening). Patients in both studies were randomized 1:1:1 to receive 1 of 2 doses of elezanumab or placebo intravenously every 4 weeks through week 48. The primary endpoint for both studies is mean overall response score (ORS; based on Expanded Disability Status Scale [EDSS], Timed 25-Foot Walk [T25FW], and 9-hole Peg Test [9HPT]-dominant and nondominant) at week 52.
Results: Overall, 208 patients enrolled in RADIUS-R and 123 in RADIUS-P. In RADIUS-R, 199 (96%) patients were diagnosed with RRMS, while 9 (4%) were diagnosed with SPMS. In RADIUS-P, 59 (48%) patients were diagnosed with PPMS, and 63 (52%) were diagnosed with SPMS. Baseline mean (SD) age was 45.7 (8.4) years (RADIUS-R) and 52.6 (7.0) years (RADIUS-P). Overall, 66% of RADIUS-R and 48% of RADIUS-P patients were women. Mean (SD) ORS components for RADIUS-R were: T25FW, 7.3 (4.0); 9HPT-dominant, 28.0 (22.5); and 9HPT-nondominant, 30.0 (23.5); EDSS (median [range]), 3.5 (1.0, 6.5). ORS components for RADIUS-P were: T25FW, 12.5 (11.2); 9HPT-dominant, 31.4 (27.6); and 9HPT-nondominant, 38.1 (37.3); EDSS, 6.0 (2.0, 7.0). Most patients used concomitant DMTs (RADIUS-R, 75%; RADIUS-P, 69%), most commonly ocrelizumab (RADIUS-R, 45%; RADIUS-P, 59%).
Conclusion: RADIUS-R and RADIUS-P are ongoing phase 2 studies investigating safety and efficacy of elezanumab as a remyelination agent.