- Also known as: BAF312
- Pharmaceutical Company:Novartis Pharmaceuticals AG
- Route and Dose of Administration: Oral (once daily)
- Type: Sphingosine-1-phosphate receptor 1 (S1P1R) modulator; immunomodulator
- Emerging Treatment for: Secondary Progressive Multiple Sclerosis
- Status: Completed phase III clinical trials
How it Works
Siponimod belongs to the same class of drugs as fingolimod (Gilenya) and 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.
Research and Results
EXPAND: Phase III Trial
The safety, tolerability and efficacy of siponimod in participants with secondary progressive MS was explored in the EXPAND study, a phase III, multicenter, randomized, double-blind, parallel group, placebo-controlled clinical trial. The study enrolled 1645 people from 31 countries 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.
Adverse Effects Reported
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.
Kappos L, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018; 391(10127):1263-1273.
Gergely P, et al. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol. 2012; 167(5):1035-47.
Kappos L, et al. Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial. Neurology (Meeting Abstracts), 12 Feb 2013.
Kappos L, et al. Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial. Mult Scler Relat Disord. 2014; 3(6):752.
Lewis ND, et al. Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3. J Immunol. 2013; 190(7):3533-40.
Selmaj K, et al. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurol. 2013; 12(8):756-67.