Novartis today announced positive results of the Phase III EXPAND study showing that oral once-daily BAF312 (siponimod) significantly reduced the risk of confirmed disability progression compared with placebo in people with secondary progressive multiple sclerosis (SPMS). SPMS is a form of MS characterized by continuous worsening of neurological function over time, independent of relapses. Topline results of EXPAND were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in London, UK.

BAF312 is an investigational selective sphingosine-1-phosphate (S1P) receptor modulator. Initial, first interpretable data from the EXPAND study show:

  • Treatment with BAF312 reduced the risk of three-month confirmed disability progression by 21% compared with placebo (p=0.013). The risk reduction for six-month confirmed disability progression was greater, further supporting robustness of the data.
  • A consistent reduction in the risk of three-month confirmed disability progression across predefined subgroups.
  • A significant difference in favor of BAF312 compared to placebo over 12 and 24 months in annualized relapse rate, the percent change in brain volume, and change from baseline in the volume of T2 lesions (brain lesions identified by a T2-weighted magnetic resonance imaging scan). The difference in change from baseline in the timed 25-foot walk test (T25FW) was not significant.
  • BAF312 was generally safe and well tolerated, with a profile comparable to other drugs in the same class.

“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,” said Vasant Narasimhan, Global Head of Drug Development and Chief Medical Officer for Novartis. “Novartis is the global leader in understanding the role of S1P receptor modulation in the treatment of MS, and the positive results of the EXPAND study are a continuation of our ongoing efforts to innovate and meet the needs of patients. These data are a positive stride forward in an unserved disease area, and we look forward to evaluating next steps with health authorities.”

EXPAND is the largest randomized, controlled study in SPMS to date. Patients enrolled in EXPAND were representative of a general SPMS population. They must have been diagnosed with SPMS and also demonstrated progression of disability in the two years prior to study. The majority of patients had non-relapsing SPMS. The mean age at study entry was 48 years, and patients had a median Expanded Disability Status Scale (EDSS) score of 6.0, which corresponds to the use of a walking aid.

Novartis will complete full analyses of the EXPAND data and evaluate next steps in consultation with health authorities. The full study results, including data from primary and secondary endpoints, will be submitted for publication.

About the EXPAND Study
The EXPAND study is a randomized, double-blind, placebo-controlled Phase III study, comparing the efficacy and safety of BAF312 versus placebo in people with secondary progressive MS (SPMS). It is the largest randomized, controlled study in SPMS to date, and included 1,651 people with SPMS from 31 countries. At the time of the study, individuals enrolled in EXPAND had a mean age of 48 years and had been living with MS for approximately 17 years. Patients had received a diagnosis of SPMS, and also demonstrated progression of disability in the two years prior to study. They also had an Expanded Disability Status Scale (EDSS) score between 3.0 and 6.5 inclusive, with a median score of 6.0, which corresponds to the use of a walking aid. Patients were randomized to receive either 2mg BAF312 or placebo in a 2:1 ratio, respectively.

The primary endpoint of the study was the time to three-month confirmed disability progression, as measured by the EDSS, versus placebo. Secondary endpoints included delay in the time to six-month confirmed disability progression based on EDSS versus placebo, the time to confirmed worsening of at least 20% from baseline in the timed 25-foot walk test (T25FW), T2 lesion volume, annualized relapse rate (ARR), and the safety and tolerability of BAF312 in people with SPMS.

About BAF312 (siponimod)
BAF312 (siponimod) is an investigational selective modulator of specific types of the sphingosine-1-phosphate (S1P) receptor. The S1P receptor is commonly found on the surface of specific cells residing in the central nervous system (CNS), that are responsible for causing CNS damage that drives loss of function in secondary progressive MS (SPMS). In-vitro studies show that BAF312 enters the brain and by binding to these specific receptors, may prevent the activation of these harmful cells, helping to reduce loss of physical and cognitive function associated with SPMS.