2025 American Academy of Neurology Abstract Website

Gabriel Pardo¹, Amit Bar-Or², Xavier Montalban³, Jin Nakahara⁴, Sarah A. Morrow⁵, Alit Bhatt⁶, Min Wu⁷, Gregory Lewis Pearce⁸, Roseanne Sullivan⁷, Anil Abeyewickreme⁹, Jérôme de Seze¹⁰, Heinz Wiendl¹¹, Stephen L. Hauser¹²
¹Oklahoma Medical Research Foundation, Oklahoma City, OK, USA, ²Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, ³Department of Neurology/Neuroimmunology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d’Hebron, Barcelona, Spain, ⁴Department of Neurology, Keio University School of Medicine, Tokyo, Japan, ⁵Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, ⁶Novartis Healthcare Pvt Ltd, Hyderabad, India, ⁷Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, ⁸Novartis Pharma AG, Basel, Switzerland, ⁹Novartis Pharmaceuticals UK Ltd, London, UK, ¹⁰University Hospital of Strasbourg, Strasbourg, France, ¹¹Klinik für Neurologie und Neurophysiologie, Universitätsklinikum Freiburg, Freiburg, Germany, ¹²UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA

Objective:

To describe long-term safety of ofatumumab and assess disability outcomes (up to 7 years) of early initiation of ofatumumab treatment versus delayed treatment (after switching from teriflunomide) in people with relapsing multiple sclerosis (pwRMS), including those recently diagnosed (≤3 years) and treatment naive (RDTN).

Background:

Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy versus teriflunomide in the phase 3 ASCLEPIOS I/II trials in pwRMS. Previously reported data up to 6 years of ofatumumab treatment demonstrated a favorable safety profile and sustained efficacy.

Design/Methods:

Safety analyses will include all participants who received ≥1 dose of ofatumumab in ASCLEPIOS I/II, APOLITOS, APLIOS, or ALITHIOS. Efficacy analyses will evaluate cumulative data up to 7 years (cutoff: 25-Sep-2024) from pwRMS randomized to ofatumumab or teriflunomide in ASCLEPIOS I/II, regardless of whether they entered the ALITHIOS open-label extension phase. Event rates of 3/6-month (m) confirmed disability worsening (3/6mCDW), progression independent of relapse activity (3/6mPIRA; CDW events without prior confirmed relapses), and relapse-associated disability worsening (3/6mRAW; disability onset <90 days from relapse) will be assessed.

Results:

Exposure-adjusted incidence rates of adverse events (AEs), serious AEs, serious infections, and malignancies remained low and consistent, with no increased risk over 6 years. Previously reported 6-year data (cutoff: 25-Sep-2023) showed that Kaplan–Meier cumulative event rates were numerically lower in pwRMS receiving continuous ofatumumab in ASCLEPIOS I/II and ALITHIOS (OMB-OMB) versus delayed treatment (TER-OMB) for 6mCDW (21.1% vs 24.8%, p=0.063), 6mPIRA (15.5% vs 16.6%), and 6mRAW (5.2% vs 5.8%). In RDTN participants, the effect size for pwRMS receiving OMB-OMB vs TER-OMB was larger (6mCDW: 16.6% vs 23.7%, p=0.033; 6mPIRA: 11.1% vs 16.8%, and 6mRAW: 4.3% vs 4.8%). Updated 7‑year safety and efficacy data will be presented at the congress.

Conclusions:

These analyses will further support long-term safety and efficacy data for ofatumumab in pwRMS, including RDTN pwRMS, informing clinical decision-making.