Siponimod shows promise as a treatment for reducing the risk for disability progression in patients with secondary progressive multiple sclerosis (MS), according to a study published in The Lancet.
Researchers conducted a randomized, double-blind, phase 3 trial of patients with secondary progressive MS that was both event- and exposure-driven. Between February 5, 2013 and June 2, 2015, 1105 patients were randomly assigned to a siponimod group (903 of whom completed the study) and 546 to a placebo group (424 of whom completed the study). Patients showed a mean time of 16.8 years since their first symptoms of MS (standard deviation 8.3), and 3.8 years since onset of secondary progressive MS (standard deviation 3.5). Of 1651 patients, 56% needed assistance walking and 64% had not had a relapse in the previous 2 years.
Of 1651 patients in both groups, 26% of those in the siponimod group and 32% of those in the placebo group had confirmed disability progression in 3 months (relative risk reduction 21%, P=.013). There were adverse events in 89% of the siponimod group and 82% of those receiving placebo, although serious adverse events affected 18% of the siponimod group and 15% of the placebo group. Among those adverse events more common in the siponimod group were increased liver transaminase concentration, convulsions, lymphopenia, macular edema, bradycardia and bradyarrhythmia at start of treatment, varicella zoster reactivation, and hypertension. There were no differences in fatalities, malignancies, or infections between the 2 groups.
This study is the result of work done in 292 international hospitals and specialist centers. Patients with secondary progressive MS were between the ages of 18 and 60 and had a score between 3.0 and 6.5 on the Expanded Disability Status Scale. These patients took oral siponimod 2 mg once daily until a set number of confirmed disability progression events occurred, with 3-month confirmed disability progression being the chief end point, for a maximum of 3 years.
Researchers concluded that “[siponimod] reduced the risk of disability progression with a safety profile similar to that of other [sphingosine 1-phosphate] modulators and is likely to be a useful treatment for [secondary progressive multiple sclerosis].”
This study was funded by Novartis Pharma AG.
Kappos L, Bar-Or A, Cree BA, et al; for the EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study [published online March 23, 2018]. Lancet. doi: 10.1016/S0140-6736(18)30475-6