March 27, 2018

Results published from a phase III study of siponimod in secondary progressive multiple sclerosis (SPMS)

Pharmaceutical company, Novartis, released findings from EXPAND, a double-blind, randomized phase III study of oral, once-daily siponimod in secondary progressive multiple sclerosis (SPMS) recently published in the renowned journal The Lancet. A commentary, by Dr. Luanne Metz and Wei-Qiau Liu (University of Calgary), on the results of the trial was also published in The Lancet.

Siponimod, a sphingosine-1-phosphate receptor modulator works by entering the central nervous system (CNS) and binding to specific subtypes of the sphingosine 1-phosphate (S1P) receptor. The S1P receptor is found on the surface of specific immune cells called T cells and B cells that play a role in causing damage to the CNS in MS. By binding to the S1P receptor, siponimod prevents these harmful immune cells – specifically B cells and both CD4+ and CD8+ T cells – from being activated and released from the lymph nodes and thymus gland into the blood circulation and, hence, the brain and spinal cord.

The study enrolled 1645 participants between the ages of 18 to 60 with SPMS and an Expanded Disability Status Scale (EDSS) score of 3.0–6.5. Participants were randomly assigned to once daily 2 mg of oral siponimod, or placebo for up to three years, or until specific evidence of disability progression was observed.

Data from EXPAND showed that siponimod met its primary endpoint of reduced risk of three-month confirmed disability progression(CDP) by 21% versus placebo. Siponimod also resulted in reduced six-month CDP by 26%. On imaging measures, siponimod slowed the rate of brain volume loss by 23% and decreased T2 lesion volume by approximately 80% over 12 and 24 months. Other results that were reported include reduced annualized relapse rate by 55%, however, no difference in the Timed 25-Foot Walk test and MS Walking Scale was observed.

The most common adverse effects reported for siponimod in the EXPAND study included low white blood count, increased liver counts, slow heart rate at treatment initiation, macular edema, high blood pressure, varicella zoster reactivation (shingles), and convulsions.

Novartis plans to file Siponimod as a treatment for people with SPMS for Health Canada approval in 2018.