Longer-term Safety and Efficacy of Ofatumumab in People with Relapsing Multiple Sclerosis for Up to 6 Years
Heinz Wiendl1, Stephen Hauser2, Jacqueline Nicholas3, Jerome De Seze4, Sven Meuth5, Paul Giacomini6, Derrick Robertson7, Sibyl Wray8, Alit Bhatt9, Xixi Hu10, Haoyi Fu10, Valentine Jehl11, Roseanne Sullivan10, Ibolya Boer11, Jeffrey Cohen12, Ludwig Kappos13
1University of Münster, Münster, Germany, 2UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States, 3OhioHealth Multiple Sclerosis Center, Columbus, OH, USA, 4University Hospital of Strasbourg, Strasbourg, France, 5Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany, 6Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, 7Multiple Sclerosis Division, Department of Neurology, University of South Florida, Tampa, FL, USA, 8Hope Neurology MS Center, Knoxville, TN, USA, 9Novartis Healthcare Pvt. Ltd., Hyderabad, India, 10Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 11Novartis Pharma A.G. Basel, Switzerland, 12Department of Neurology, Mellen MS Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA, 13Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) and MS Center, Departments of Headorgans, Spine and Neuromedicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland
Objective:

To assess ofatumumab’s longer-term safety and efficacy for up to 6 years in people with relapsing multiple sclerosis (pwRMS).

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 for up to 5 years demonstrated sustained efficacy and a favorable safety profile in pwRMS.

Design/Methods:

Efficacy analyses will include all participants randomized in ASCLEPIOS I/II and their data from first dose in ASCLEPIOS I/II, whereas safety analyses will include all participants who received at least one dose of ofatumumab in either ASCLEPIOS I/II, APOLITOS, APLIOS, or ALITHIOS (cut-off date: 25-Sep-2023). Efficacy will be analyzed by the randomized treatment in the core study, with those randomized to ofatumumab referred to as continuous group and to teriflunomide as switch group.


Results:

Mean baseline age in ASCLEPIOS I/II (N=1882) was ~38 years, ~67.6% were female, and mean EDSS was ~2.9 in both groups. Previously reported 5-year data (cut-off: 25-Sep-2022) showed a sustained low annualized relapse rate (ARR) and sustained and almost complete suppression of MRI lesion activity in the continuous group. In the switch group, ARR was markedly reduced from Year 2–3 (0.16–0.06) and remained low through Years 3–5 (0.05). MRI lesion activity was almost completely suppressed through Years 3–5. At Year 5, 9 of 10 patients reached NEDA-3 in both groups. Exposure-adjusted incidence rate of adverse events (AEs), serious AEs, serious infections, and malignancies remained consistent with no increased risk over 5 years. Mean IgG levels remained stable (>lower limit of normal [LLN]: 5.65 g/L), while mean IgM levels decreased but remained >LLN (0.4 g/L). Updated 6-year efficacy and safety results will be presented at the congress.

 

Conclusions:

These analyses will help inform physicians on the longer-term safety and efficacy profile of ofatumumab in pwRMS.

 

10.1212/WNL.0000000000205570