The drug, Kesimpta (ofatumumab), received approval from the U.S. Food and Drug Administration (FDA) for use in these forms of MS and related conditions, on August 20, or roughly 10 weeks after its manufacturer, Novartis, announced that the agency would delay its evaluation. An IV infusion preparation of ofatumumab, sold as Arzerra, has been used for years to treat certain forms of leukemia. Novartis expects Kesimpta to be available in the United States by September. “Ofatumumab provides an additional option for the treatment of MS,” says Jeffrey Cohen, MD, the director of the Mellen Center for MS at the Cleveland Clinic in Ohio. “It has the advantage of high efficacy combined with good safety and tolerability, and it’s administered at home.” The drug has been described as a precision targeted B-cell agent that’s part of the fully human anti-CD20 monoclonal antibody class. In other words, Kesimpta depletes a certain type of immune B cells that are believed to cause the nervous system damage that occurs in MS. Kesimpta is in the same drug class as Ocrevus (ocrelizumab), which works similarly but is infused intravenously twice a year. Kesimpta’s dosing mechanism, a Sensoready auto-injector pen, is similar to the type of device some people with diabetes use to take insulin, and it’s an added benefit for those “who want to avoid having to go to a medical facility for infusion [because of] the associated cost and potential exposure to COVID-19,” Dr. Cohen notes.
Fewer Brain Lesions, Less Disability
In the phase 3 ASCLEPIOS I and II clinical trials, the final results of which were published in August 2020 in the New England Journal of Medicine (NEJM), ofatumumab reduced annualized relapse rates (ARRs) in people with MS by more than 50 percent compared with Aubagio (teriflunomide), an oral drug used to treat the condition. Researchers also observed up to 97 percent reductions in gadolinium-enhancing (Gd+) T1 lesions and up to 85 percent drops in new or enlarging T2 lesions on magnetic resonance imaging (MRI) in those treated with ofatumumab. These lesions, visible on MRI scans of the brain, are signs of worsening MS. In addition, research has shown that treatment with ofatumumab reduces the risk for three-month and six-month progression of disability, based on results from the Kurtzke Expanded Disability Status Scale, by more than 30 percent, according to the authors of the NEJM paper. In a statement, one of them, Stephen L. Hauser, MD, the director of the Weill Institute for Neurosciences at the University of California in San Francisco, described the FDA approval as “wonderful news for patients with relapsing multiple sclerosis,” adding that “in the key clinical studies, [it] … produced a profound reduction in new brain lesions [and] relapses and slow[ed] underlying disease progression.”
‘Good Safety and Tolerability’
The most common observed side effects in the phase 3 trials were injection-site reactions, which occurred in 20 percent of those treated with ofatumumab and in 15 percent of those who received teriflunomide. In addition, nasopharyngitis (or the common cold), headache, upper respiratory tract infection, and urinary tract infection occurred in more than 10 percent of people treated with ofatumumab, with serious infections reported in 2.5 percent of those on the drug. “Ofatumumab’s efficacy is comparable with that of alemtuzumab [Lemtrada], natalizumab [Tysabri], and ocrelizumab, with good safety and tolerability,” Cohen says. “It will be useful for people who haven’t achieved adequate [symptom] control with other medications or who aren’t tolerating them, and it will likely serve as the initial medication for a sizable proportion of people diagnosed with MS.”
