Secondary progressive MS can follow on from relapsing-remitting MS, the most common form of the disease. People with secondary progressive MS experience a gradual worsening of their condition as disability accumulates. There are currently no approved treatment options for this form for MS, making clinical trials in this area hugely important in identifying new therapies for this group of people with MS.
A new, international clinical trial has just published encouraging results of the drug siponimod in people with secondary progressive MS. The results from the Phase III trial, published in the prestigious journal The Lancet*, have shown that siponimod is able to reduce the risk of progression in people with secondary progressive MS.

In addition, brain changes measured using MRI showed that siponimod decreased the amount of brain tissue loss and the number of new and active lesions in people taking the treatment. Objective walking tests and patient reported walking ability did not show improvement. The trial took place in 31 centres around the world and compared results from 1099 people with secondary progressive MS who were given siponimod to those from 545 people who received placebo tablets. Early results of this clinical trial, known as EXPAND, were released in August 2016*.


Siponimod is an oral treatment that belongs to the same class of drugs as fingolimod . It targets a molecule found on the surface of cells called the sphingosine-1-phosphate (S1P) receptor. This receptor is found on the cells in the immune system, brain and spinal cord that may contribute to the ongoing damage to myelin and nerves that occurs in secondary progressive MS.

Participants in the trial were treated for up to three years and their disability was tracked every three months to assess whether or not the siponimod was working. Participants were considered to have confirmed disability progression if their disability (as measured by the Expanded Disability Status Scale) worsened and if this persisted over the next three months. They were also tested on the amount of time it took to walk a certain distance and their walking ability (rated by the patient).
Over the course of the clinical trial, 26% of the people taking siponimod had a progression of their level of disability, compared to32% of the people who were not treated with siponimod. This was equivalent to a 21% reduction in the risk of disability progression in this trial.

Participants did not show improvements in the timed walking test, nor did they report significant differences in their walking ability. In the group of people taking siponimod, there was an improvement in the number of relapses over the course of a year (known as the annualised relapse rate) and the amount of time before a new confirmed relapse. .
Participants taking siponimod also showed improvements on MRI scans taken at one and two year time points. The rate of brain tissue loss (shrinkage or atrophy) was slower and they had lower numbers of new or active lesions present on their MRI scans.

The analysis also showed that siponimod was more effective in people who were younger, had less disability and had a shorter disease duration.

In terms of side effects, some of those seen more frequently in the group taking siponimod were related to low white blood cell counts in the blood and cardiac and liver abnormalities. These side effects were in line with other treatments used for MS in this class.

Although the changes seen to disability in this clinical trial were small, the research team notes that, ‘for patients with secondary progressive MS, even numerically small changes in EDSS score can correspond to substantial changes in neurological function and daily activities.’

While results are mixed, they are encouraging for people with secondary progressive MS, for whom there is currently no approved treatment option available.

With thanks to MS Research Australia – the lead provider of research summaries on our website.