Positive phase III results showing efficacy of BAF312 (siponimod) in patients with secondary progressive MS

 

Background

Siponimod (also known as BAF312) is an experimental immune system-modulating therapy. Siponimod is thought to act by retaining/constraining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and preventing them from entering the central nervous system. Siponimod also effectively accesses the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory or other effects. Siponimod is similar to another MS treatment – fingolimod (known as Gilenya®), but it has a more targeted effect on white blood cells and therefore may have fewer side effects compared to fingolimod while maintaining similar beneficial effects.

Siponimod previously demonstrated safety and efficacy on MRI scans in a phase II study in people with relapsing-remitting MS (The Lancet Neurology, 2013 Aug; 12(8):756-67).

 

The Study

Participants were randomly assigned to take siponimod or placebo capsules daily for up to 60 months. The primary endpoint of the study was reducing the risk of disability progression, as measured by the EDSS scale at three months. According to an August 25, 2016 press release from Novartis, siponimod achieved this endpoint compared with placebo. Secondary endpoints included reducing the risk of disability progression as measured by the EDSS at six months versus placebo, the risk of worsening mobility as measured by the timed 25-foot walk test, disease activity as observed on MRI scans, relapse rate, and safety/tolerability.

 

Results

Results were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on September 17, 2016. The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression (confirmed at 3 months) compared to those on placebo. Secondary endpoints suggested that those on active therapy had at 26% reduced risk of disability progression (confirmed at 6 months), a 23.4% lower average change in brain volume, and reduced lesion volume. There was no significant difference seen between groups in the timed 25-foot walk. Relapse rates were significantly lower in those taking siponimod.

 

Safety

The therapy was generally well tolerated and similar to adverse events reported for similar compounds. Serious adverse events occurred in 16.7% of participants. The serious adverse events reported to be more likely for those taking siponimod included nervous system disorders and infections.

We are encouraged by industry investment in support of this important study focusing on secondary progressive MS, for which there are few treatment options. While the reported results on progression are modest, they indicate benefit for people with a range of disability levels, and we hope they will lead to a much needed treatment advance for people living with secondary progressive MS.

Professor Alan Thompson, Chair of the International Progressive MS Alliance Scientific Steering Committee.

 

The Alliance will continue to monitor all potential area of progress and increased understanding in order to accelerate the development of treatment for people with progressive MS.

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