#ECTRIMS2016 – Novartis’s Siponimod Appears to Slow SPMS Progression in Phase 3 Study

A presentation at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016 Congress gave patients with progressive multiple sclerosis (MS) a reason for optimism, as Novartis reported that siponimod (BAF312) reduced the risk of disability progression in a Phase 3 study of patients with secondary progressive (SP) MS.

The data was presented during the “Late Breaking News” session on the last day of the meeting, held Sept. 14-17 in London, and titled “Efficacy and safety of siponimod in secondary progressive multiple sclerosis – results of the placebo controlled, double-blind, Phase III EXPAND study.”

Siponimod is an oral drug acting on two specific types of the sphingosine-1-phosphate receptor. When the drug binds to the receptor on immune lymphocytes, they become more likely to remain in the lymph tissue instead of entering the brain and spinal cord. The same receptor is found on brain cells that researchers believe contribute to the development of SPMS.

“There are very few available treatment options to delay disease progression in SPMS, and there is a high unmet need for effective therapies with an acceptable safety profile for people with the condition,” Vasant Narasimhan, global head of drug development and chief medical officer for Novartis, said in a news release.

The Phase 3 EXPAND study (NCT01665144) is the largest randomized clinical trial of SPMS to date, and included 1,651 patients from 31 countries randomized to receive either 2 mg once daily of siponimod or a placebo. For every two patients treated with the drug, one received a placebo. The enrolled patients all had a moderate disability level, ranging from 3.0 to 6.5 on the Expanded Disability Status Scale (EDSS).

Patients included in the study had documented disability progression for at least two years before the start of the study, and most patients had a non-relapsing form of the disease.

The trial was composed of a core and an extension part, with 1,363 patients completing the first core phase of a maximum of three years. Most patients (87 percent) were followed for at least one year, and the median follow-up time was 21 months.

The study was designed so that the drug or placebo treatment was stopped if a patient experienced a predetermined number of confirmed disability progression events. The main goal of the trial was to prolong time to disability progression, measured by EDSS.

Findings showed that siponimod reduced the risk of progression by 21 percent when looking at three-month intervals. When analyzing disease progression in six-month intervals, the effect was even greater. This slowing of disability progression was seen in different types of patients, including those who did not have relapses.

“The outcome of the EXPAND study is very encouraging, and shows BAF312 is effective at reducing the risk of confirmed disability progression in people with SPMS,” Frank Dahlke, Novartis global program head of neuroscience, told Multiple Sclerosis News Today. “SPMS leads to progressive, irreversible disability, and the EXPAND data are very good news indeed for patients and the medical community, given the devastating nature of the disease.”

Researchers also reported that siponimod reduced the yearly relapse rate, brain volume loss, and the volume of brain lesions measured by MRI. However, the drug did not improve performance on the timed 25-foot walk test (a test to measure exercise capacity).

Novartis is now working to complete the analysis of data from the EXPAND study, and is in contact with health authorities discussing how to move forward.