Patients with secondary progressive multiple sclerosis (SPMS) who were treated with BAF312 (siponimod), a sphingosine-1-phosphate (S1P) inhibitor, in a Phase 3 clinical trial showed a significantly reduced risk for disability progression compared to placebo, Novartis recently announced.
BAF312 is a selective modulator of specific types of the S1P receptor. This receptor is commonly found at the surface of immune cells that infiltrate and induce damage in the central nervous system (CNS), leading to loss of function in MS patients. Similar to Gilenya (fingolimod), BAF312 works by binding to these specific receptors and preventing the migration and activation of immune cells in the CNS. BAF312, however, binds more selectively to specific S1P receptors than Gilenya, particularly to S1P-1 and S1P-5, and is thus expected to avoid lymphopenia (an abnormally low level of lymphocytes, a type of white blood cell, in the blood), one of the more common side effects of Gilenya.
The EXPAND Phase 3 study (NCT01665144) is designed to compare the efficacy and safety of BAF312 versus placebo in patients with SPMS. It is the largest randomized, controlled study in SPMS to date, and enrolled 1,651 patients from 31 countries. Participants were randomized to receive either BAF312 at 2 mg per day or placebo in a 2:1 ratio, respectively, for a maximum of about three years. EXPAND began in December 2012 and is expected to finish in August 2017.
The study’s primary endpoint is an improvement in the time to three-month confirmed disability progression compared to placebo, measured using the Expanded Disability Status Scale (EDSS). Secondary endpoints include time to confirmed worsening of at least 20 percent in the timed 25-foot walk test, delay in the time to six-month confirmed disability progression, T2 lesion volume, annualized relapse rate, and the safety and tolerability of BAF312.
Novartis researchers will detail results from the trial’s primary and secondary endpoints in a late-breaking oral presentation at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in London. The presentation is to take place on Sept. 17.
“SPMS is a particularly disabling form of MS, and there is a need for effective treatment options to help delay disability progression in those living with the condition,” Vasant Narasimhan, global head of Drug Development and chief medical officer for Novartis, said in a press release. “The positive EXPAND data are encouraging for a disease with such a high unmet need. We look forward to sharing the results at the upcoming ECTRIMS congress, and thank all of the study participants and investigators.”
Novartis is also the maker of Gilenya (fingolimod), which was approved by the U.S. Food & Drug Administration (FDA) to treat relapsing forms of MS in 2010.