FDA Approves Siponimod to Treat Relapsing Forms of MS

The US Food and Drug Administration (FDA) has approved siponimod (Mayzent®) tablets to treat adults with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease (SPMS).

In a randomized, double-blind, placebo-controlled study, investigators found siponimod reduced the risk of 3-month confirmed disability progression (CDP) in patients by 21% versus the placebo group and a 33% reduction in patients who had relapse activity in the two years prior to screening.

Novartis announced siponimod is expected to be available within the US in approximately 1 week.

“Multiple sclerosis can have a profound impact on a person’s life,” said Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research. “We are committed to continuing to work with companies that are developing additional treatment options for patients with multiple sclerosis.”

Efficacy of siponimod was shown in the phase 3 EXPAND study that compared it to placebo in patients with SPMS who had evidence of disability progression in the prior two years and no relapses in the 3 months prior to enrollment. A total of 1651 patients were included in the study with a mean age of 48 years and more than 50% had a median Expanded Disability Status Scale score of 6.0 and relied on a walking aid.

The primary endpoint of the study was the time to 3-month CDP. The fraction of patients with CDP was significantly lower in the siponimod group than in the placebo group. Investigators noted a 21% reduction versus the placebo in risk of 3-month CDP and a 33% reduction in patients who had relapse activity in the two years prior to screening. Additionally, siponimod decreased the annualized relapse rate in patients by 55%. Investigators determined that in the subgroup of patients with non-active SPMS the results were not statistically significant.

“Mayzent is a testament to the Novartis mission to reimagine medicine. We are delighted that our ongoing commitment to stop MS has led to a much awaited treatment for these patients in need,” said Paul Hudson, chief executive officer of Novartis Pharmaceuticals.

Siponimod must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Siponimod may cause macular edema, transient decreases in heart rate, a decline in liver function, and could increase a patient’s risk of infection. Women of childbearing potential should use effective contraception during and for 10 days after stopping use of siponimod. Health care professionals should monitor patients for posterior reversible encephalopathy syndrome and monitor patients that had treatment with immunosuppressive/immune-modulating therapies because there may be unintended additive immunosuppression with siponimod.

The most common adverse reactions (greater than 10%) reported by patients receiving siponimod in the clinical trials include headache, high blood pressure, and liver function test increases.

Novartis noted that time of availability for siponimod may vary as healthcare providers integrate it into their practices. Regulatory action for siponimod in the European Union is anticipated in late 2019, with additional regulatory action anticipated in Switzerland, Japan, Australia, and Canada this year.

Bruce Bebo, PhD, executive vice president of research at the Nation MS Society, expressed excitement over the potential of siponimod.

"We are grateful that there is a new treatment option for adults with active secondary progressive MS,” Bebo said. “We are hopeful this approval will stimulate a conversation between patients and healthcare professionals about disability progression after relapsing remitting MS and its early management.”