ASCLEPIOS trials: Ofatumumab reduces relapse rates in MS
Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide, according to a pair of phase 3 randomized controlled trials published in The New England Journal of Medicine.
Ofatumumab (Novartis) is a subcutaneous anti-CD monoclonal antibody that selectively depletes B cells. Teriflunomide (Sanofi Genzyme) is an oral inhibitor of pyrimidine synthesis that lowers T-cell and B-cell activation, according to Stephen L. Hauser, MD, director of the University of California, San Francisco Weill Institute for Neurosciences, and colleagues.
In the ASCLEPIOS I and II clinical trials, 1,882 patients with relapsing multiple sclerosis in 37 countries were randomly assigned to receive 20 mg of ofatumumab every 4 weeks after 20 mg loading doses at days 1, 7 and 14, or 14 mg of teriflunomide daily. Patients received treatment for up to 30 months.
Hauser and colleagues found that after a median of 1.6 years, the annualized relapse rates in ASCLEPIOS I were 0.11 in the ofatumumab group and 0.22 in the teriflunomide group (difference = –0.11; 95% CI, –0.16 to –0.06). In ASCLEPIOS II, the rate was 0.1 in the ofatumumab group and 0.25 in the teriflunomide group (difference = –0.15; 95% CI, –0.2 to –0.09).
Pooling the trial results together, the percentage of patients with worsening disability at 3 months was 10.9% among ofatumumab recipients and 15% among teriflunomide recipients (HR = 0.66; P = .002). At 6 months, that percentage was 8.1% in the ofatumumab group and 12% in teriflunomide group (HR = 0.68; P = .01).
In addition, the percentage of patients with improvement in disability at 6 months was 11% in the ofatumumab group and 8.1% in the teriflunomide group (HR = 1.35; P = .09). The number of gadolinium-enhancing lesions per T-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels — but not the change in brain volume — followed the same pattern as the annualized relapse rate, the researchers said.
Injection-related reactions occurred in 20.2% of ofatumumab recipients and 15% of teriflunomide recipients, who received placebo for this part of the trial, according to the researchers. Serious infections occurred in 2.5% of ofatumumab recipients and 1.8% of teriflunomide recipients.
Hauser said that the results are part of a paradigm shift in MS that has occurred in recent decades.
“While there is not yet a cure, a generation ago MS patients typically became cane- or crutch-dependent within 15 or 20 years, but now they often are spared from significant disability,” he said in a press release. “The improvement in MS treatment, especially with drugs that specifically target B cells, is one of the great success stories of medicine."
According to Novartis’ website, the FDA is expected complete its review of ofatumumab’s supplemental biologics license application in September.
Editor’s note: This story was updated to include the drugs’ generic names to avoid reader confusion.
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In patients with relapsing-remitting multiple sclerosis, ofatumumab was found to have lower relapse rates than teriflunomide and was also superior in suppressing lesion activity on MRI.
That being said, the efficacy of ofatumumab compared with other drugs for MS that are more potent than teriflunomide cannot be deduced from this study alone. Further trials are necessary to determine the long-term safety profile and efficacy of ofatumumab compared with existing disease-modifying therapies, particularly other anti-CD20 monoclonal antibodies.
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