Novartis' Anti-CD20 Antibody Ofatumumab Reduces Annualized Relapse Rate by Over 50% in Phase III Trials for Relapsing Multiple Sclerosis

Novartis announced today that The New England Journal of Medicine (NEJM) will publish tomorrow the positive results from the Phase 3 ASCLEPIOS I and II trials of ofatumumab, an anti-CD20 antibody developed by the company, for the treatment of relapsing multiple sclerosis (RMS) in adults. Both studies met their primary endpoints.

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) that disrupts the normal functioning of the brain, optic nerves, and spinal cord through inflammation and tissue damage. The progression of MS leads to increasing loss of physical function (e.g., walking) and cognitive function (e.g., memory). There are three main types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). RRMS is characterized by clearly defined episodes of relapse and remission, i.e., relapses, attacks, or worsening of symptoms, followed by periods of partial or complete recovery. Globally, there are approximately 2.3 million people with MS, and about 85% of them are initially diagnosed with RRMS.

Ofatumumab is a fully humanized CD20 antibody. By binding to CD20 on the surface of B lymphocytes, it clears B cells from the bloodstream—cells that play a key role in triggering autoimmune responses in patients with multiple sclerosis (MS). This therapy allows for once-monthly subcutaneous administration at home. It not only offers convenience for disease management but also enables more targeted depletion of B cells in lymph nodes while sparing B cells in the spleen. Previously, ofatumumab had already received FDA approval as a treatment for leukemia. The U.S. FDA accepted the supplemental Biologics License Application (sBLA) for ofatumumab in February this year and is expected to issue a decision by September.

ASCLEPIOS I and II were two identical, randomized, double-blind, Phase 3 clinical trials with active comparators. The trial results demonstrated that, compared with the active comparator, ofatumumab reduced the annualized relapse rate (ARR) in multiple sclerosis (MS) by 51% and 58%, respectively, in the two trials (p<0.001). The key secondary endpoints related to delaying disease progression were also met; compared with the active comparator, the risk of confirmed disability progression (CDP) in MS was reduced by 34% at 3 months (p=0.002) and by 32% at 6 months (p=0.01). Furthermore, the safety profile of ofatumumab was consistent with data from previous Phase 2 studies.

Professor Stephen L. Hauser, Director of the Weill Institute for Neurosciences at the University of California, San Francisco (UCSF), and Co-Chair of the Steering Committees for the ASCLEPIOS I and II studies, stated: “The ASCLEPIOS studies demonstrated that ofatumumab significantly reduces new inflammatory activity, as well as clinical relapses and progression events. It represents a potential new option for patients with RMS, offering favorable efficacy and safety profiles, along with the convenience of once-monthly self-administration without the need for infusions.”

References:

[1] Novartis announces NEJM publication of Phase III ASCLEPIOS trials demonstrating superior efficacy of ofatumumab in patients with relapsing multiple sclerosis. Retrieved August 5, 2020, from https://www.prnewswire.com/news-releases/novartis-announces-nejm-publication-of-phase-iii-asclepios-trials-demonstrating-superior-efficacy-of-ofatumumab-in-patients-with-relapsing-multiple-sclerosis-301107052.html

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