Jun-Ichi Kira1, Jin Nakahara2, Denis V Sazonov3, Takayoshi Kurosawa4, Isao Tsumiyama4, Roman Willi5, Martin Zalesak5, Ratnakar Pingili6, Dieter A Häring5, Krishnan Ramanathan5, Bernd C Kieseier7, Martin Merschhemke5, Wendy Su6, Takahiko Saida8. 1. Translational Neuroscience Center, Graduate School of Medicine, Fukuoka Central Hospital, International University of Health and Welfare, Fukuoka, Japan/Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Fukuoka, Japan. 2. Department of Neurology, Keio University School of Medicine, Tokyo, Japan. 3. Siberian District Medical Centre, Federal Medical and Biological Agency of Russia, Novosibirsk, Russia. 4. Novartis Pharma KK, Tokyo, Japan. 5. Novartis Pharma AG, Basel, Switzerland. 6. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. 7. Novartis Pharma AG, Basel, Switzerland/Department of Neurology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany. 8. Kansai Multiple Sclerosis Center and Kyoto Min-iren Central Hospital, Kyoto, Japan.
Abstract
BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. OBJECTIVE: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. METHODS: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. RESULTS: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% (p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. CONCLUSION: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.
BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. OBJECTIVE: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. METHODS: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. RESULTS: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% (p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. CONCLUSION: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.
Authors: Anne H Cross; Silvia Delgado; Mario Habek; Maria Davydovskaya; Brian J Ward; Bruce A C Cree; Natalia Totolyan; Ratnakar Pingili; Linda Mancione; Xixi Hu; Roseanne Sullivan; Wendy Su; Ronald Zielman; Ayan Das Gupta; Xavier Montalban; Kevin Winthrop Journal: Neurol Ther Date: 2022-03-13
Authors: Stephen L Hauser; Anne H Cross; Kevin Winthrop; Heinz Wiendl; Jacqueline Nicholas; Sven G Meuth; Paul S Giacomini; Francesco Saccà; Linda Mancione; Ronald Zielman; Morten Bagger; Ayan Das Gupta; Dieter A Häring; Valentine Jehl; Bernd C Kieseier; Ratnakar Pingili; Dee Stoneman; Wendy Su; Roman Willi; Ludwig Kappos Journal: Mult Scler Date: 2022-03-01 Impact factor: 5.855