Siponimod Approved by FDA for Treatment of Relapsing-Remitting and Secondary-Progressive Multiple Sclerosis

The first drug to treat 3 phases of multiple sclerosis (MS), secondary-progressive MS (SPMS), relapsing-remitting MS (RRMS), and clinically isolated syndrome (CIS), has been approved by the Food and Drug Administration (FDA). Siponimod (Mayzent; Novartis, East Hanover, NJ) is an oral agent approved for treatment of adults with RRMS, SPMS with active disease, and CIS—the earliest form of MS. Considered as the first clinically significant episode of MS, CIS is defined as an attack of neuroinflammation or demyelination lasting more than 24 hours. Siponimod will be made available in the coming weeks as healthcare providers and payors integrate the treatment into their practices. 

Before starting siponimod, it is necessary to check patients’ liver enzyme (CYP) genotype and obtain an ECG and cardiovascular risk profile. Siponimod is contraindicated for patients with CYP2C9*3/*3 genotype and cardiovascular risk factors. Vaccination status should also be assessed because risk of infections increases with treatment. The most common side effects are headache, hypertension, and transaminase elevation; macular edema is a rare but serious side effect.

"We are grateful that there is a new treatment option for adults with active SPMS," said Bruce Bebo, PhD, Executive Vice President, Research, National MS Society. "We are hopeful this approval will stimulate a conversation between patients and healthcare professionals about disability progression after RRMS. . ."

Approval is based on the EXPAND study (NCT) in which treatment with siponimod significantly reduced the risk of 3-month confirmed disability progression (CDP) by  21% vs placebo (P = .013) in participants with all stages of MS. Participants who had active relapses in the 2 years before starting treatment had a 33% reduction in CDP when compared with treatment with placebo (P = .01). Treatment with siponimod also reduced annualized relapse rate (ARR) by 55%. Although there was no significant difference in the timed 25-foot walk test (T25FW), T2 lesion volume and gadolinium-enhancing lesions were reduced by 79% and 89%, respectively, in those given siponimod vs placebo.  

Siponimod selectively modulates the sphingosine 1-phosphate (S1P) receptor to prevent lymphocytes from leaving lymph nodes and entering the central nervous system (CNS). The drug also crosses the blood-brain barrier and binds to S1P receptors on oligodendrocytes and astrocytes, which is thought to directly prevent inflammation.

Bruce Cree, MD, PhD, MAS, EXPAND Steering Committee member and Clinical Research Director and George A. Zimmermann Endowed Professor in Multiple Sclerosis, University of California, San Francisco, School of Medicine said,"Importantly, healthcare professionals now have even more reason to help patients identify changing symptoms and uncover early signs of progression."