Conference Coverage

What Is the Future of Disease-Modifying Therapies for MS?


 

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COPENHAGEN—The many drugs in development for multiple sclerosis (MS) have various modes of action and could increase patients’ treatment options, according to an overview presented at the 29th Congress of the European Committee for Treatment and Research in MS. If these drugs reach the market, they may make it difficult for neurologists to stratify patients to various treatment regimens, but they will open new possibilities such as combination therapies, said Tobias Derfuss, MD.

Laquinimod Reduced Disability Progression
Two recently completed phase III trials found that laquinimod, a drug that appeared to promote remyelination in animal models, reduced patients’ annualized relapse rate by 20%. The drug also was associated with a “surprising” 46% reduction in disability progression, said Dr. Derfuss, Cohead of the Outpatient Care Unit and the Neuroimmunological Research Group at the University Hospital Basel. “You expect this effect on disability progression only if you also have a strong effect on the inflammatory components or [if] the drug has an impact on neuroprotection,” he said.

In addition, laquinimod reduced patients’ rate of brain atrophy by 30% during a 24-month period, which indicated that the drug might have a neuroprotective effect. New trials are required to identify the optimal dose and determine whether the drug could be part of a combination therapy.

Siponimod Decreased the Number of Unique Active Lesions
Siponimod is an oral compound in development that acts on the sphingosine-1-phosphate receptor. A phase II trial that compared siponimod to placebo in patients with relapsing-remitting MS suggested that 2 mg was the most effective dose of the drug. Compared with placebo, siponimod reduced unique active lesions at three months.

Investigators are recruiting participants for a phase III trial of siponimod in patients with secondary progressive MS. The trial will continue until a certain number of patients have three-month confirmed disability progression, which is the primary end point. When patients have six-month confirmed disability progression, they will be given the option of switching to open-label treatment. “This trial is a very good option for patients with secondary progressive MS,” said Dr. Derfuss.

Simvastatin May Reduce Brain Atrophy
Researchers have investigated the efficacy of statins in treating relapsing-remitting MS, and a double blind placebo-controlled trial in 2012 evaluated the efficacy of 80 mg/day of simvastatin in patients with secondary progressive MS. The drug was associated with significant reduction in brain atrophy, as well as with reductions in Expanded Disability Status Scale score and the MS Impact Scale, a patient-related outcome.

The results are surprising, in light of the trial’s small patient population, said Dr. Derfuss. In all, 140 patients participated in the trial, which lasted for two years. “We know from other trials in secondary progressive MS [that] it might take longer to see the effect,” said Dr. Derfuss. But because simvastatin no longer has patent protection, he added, pharmaceutical companies may be unwilling to conduct larger phase III trials, which means that MS societies and independent research organizations may have to provide the necessary funding.

Monoclonal Antibodies May Improve Patients’ Outcomes
Several monoclonal anti­bodies in development also show promise for the treatment of MS. Investigators recently completed a phase II trial that tested two doses of daclizumab, an IL-2 receptor antagonist, for one year. Compared with placebo, daclizumab reduced patients’ annualized relapse rate by more than 50%. An extension study and another phase IIb trial have supported the treatment’s efficacy. Daclizumab is a “promising drug” that has an “impressive effect on disability progression” within a short time, said Dr. Derfuss.

Secukinumab is a fully humanized antibody against the IL-17A cytokine. Patients in a small trial received 10 mg/kg/day of secukinumab. Despite the trial’s brief duration, researchers observed a significant reduction in new gadolinium-enhancing lesions among patients receiving secukinumab. Patients in the treatment arm also had a reduction in relapse rates, but it was not statistically significant. Investigators are recruiting patients for a second, larger phase II trial.

Ocrelizumab, a third antibody, depletes the body’s B-cells. A recent phase II trial compared ocrelizumab with interferon beta-1a and placebo. After eight weeks, patients who received ocrelizumab had a significant reduction in gadolinium-enhancing lesions, compared with patients receiving placebo and those receiving interferon. Ocrelizumab also reduced relapse rates. Two phase III trials are studying ocrelizumab for primary progressive MS, and one trial is evaluating ocrelizumab as a treatment for relapsing-remitting MS.

Erik Greb
Senior Associate Editor

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