Siponimod Reduces Risk of SPMS Patients’ Disability Worsening, Phase 3 Trial Shows

Siponimod (BAF312) reduces the risk of disability progression in patients with secondary progressive multiple sclerosis (SPMS), a Phase 3 clinical trial shows.

An article about the Novartis therapy’s trial results appeared in the journal The Lancet. The title is “Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study.”

The EXPAND trial (NCT01665144) covered 1,651 SPMS patients in 31 countries who were randomized to receive 2 mg of siponimod orally or a placebo once a day. The participants had moderate to severe disability, with scores on the Expanded Disability Status Scale (EDSS) ranging from 3.0 to 6.5

Siponimod reduced patients’ three-month disability progression scores by 21 percent and their six-month scores by 26 percent, compared with a placebo.

In addition, siponimod slowed patients’ brain shrinkage by 23 percent compared with a  placebo, and reduced by 55 percent patients’ annualized relapse rate after two years.

Another finding was that the therapy reduced by 80 percent the progression of brain lesions detected by imaging methods.

“These data are all the more impressive when considering that the majority of patients already had advanced disability when starting treatment in EXPAND,” Ludwig Kappos, a professor at University Hospital Basel in Switzerland, said in a press release. He was principal investigator of the trial.

Given the trial’s promising results, the company plans to submit a marketing application  for siponimod soon to the U.S. Food and Drug Administration. It would ask for its approval as a disease-modifying therapy for SPMS.

The company plans a filing with the European Medicines Agency in the third quarter of 2018.

“The pivotal EXPAND data provides patients, and the medical community alike, with hope that a much-needed, safe and effective treatment option is on the horizon for SPMS, for which treatment options are scarce,” said Danny Bar-Zohar, the global head of neuroscience development at Novartis. “We look forward to continuing to work with regulatory agencies to make siponimod available for these patients as fast as possible.”

Siponimod inhibits the activity of two sphingosine-1-phosphate receptors on the surface of immune cells, preventing the cells from traveling to the brain and spinal cord, where they can do damage. This means that siponimod reduces the inflammatory process that contributes to SPMS.

The EXPAND trial also showed that siponimod was safe, with patients who received it having a similar number of serious adverse events as the placebo patients.

Some adverse events were more frequent in siponimod-treated patients than in the placebo group, however. They included lower levels of immune cells in the blood, higher levels of liver enzymes, and slower heart rates, high blood pressure, and varicella infections.