Secondary progressive MS is the form of MS that 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 to identify new therapies for this group of patients.
A new international Phase III clinical trial has just published encouraging results of the drug siponimod in people with secondary progressive MS. The results, published in the prestigious journal The Lancet and backed by pharmaceutical company Novartis, have shown that siponimod is able to reduce the risk of progression in people with secondary progressive MS. Early results of this clinical trial, known as EXPAND, were released in August 2016 (read our article here).
The trial took place in 31 centres around the world and compared 1099 people with secondary progressive MS who took siponimod with 545 people who were in the placebo arm (given dummy tablets). Siponimod is an oral treatment that belongs to the same class of drugs as fingolimod (Gilenya). It targets a molecule found on the surface of cells called the sphingosine-1-phosphate (S1P) receptor. This receptor is found on cells of the immune system and also in the brain and spinal cord that may contribute to the ongoing damage to myelin and nerves that occurs in secondary progressive MS.
People in the clinical trial were treated for up to three years and their disability was tracked every three months to see if 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 this persisted over the next three months. They were also tested on the amount of time it took to walk a certain distance and walking ability rated by the patient. Brain changes were also measured using magnetic resonance imaging (MRI).
Over the course of the clinical trial, 26% of the people taking siponimod had a progression of their level of disability. 32% of the people who were not treated with siponimod had disability progression. 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 patients report significant differences in their walking ability. The number of relapses over the course of a year (known as the annualised relapse rate) and the amount of time until a new confirmed relapse were both improved in the group of people taking siponimod.
Participants taking siponimod also showed improvements on MRI, taken at one and two year timepoints. They had the rate of brain tissue loss (shrinkage or atrophy) was slower, as well as lower numbers of new or active lesions on their MRIs.
The analysis also showed that siponimod was more effective in people who were younger, had less disability and had a shorter disease duration.
Some side effects were seen more frequently in the group taking siponimod including some related to have low white blood cell counts in the blood, cardiac and liver abnormalities. These side effects were in line with other treatments used for MS in this class.
While the changes seen to disability in this clinical trial were small, the authors state ‘For patients with secondary progressive MS, even numerically small changes in EDSS score can correspond to substantial changes in neurological function and daily activities’. And while the results are mixed, they are encouraging for people with secondary progressive MS, who currently have no approved treatment option available to them.
Fast-tracking research that will lead to treatments for people with progressive forms of MS is the goal of the International Progressive MS Alliance. MS Research Australia is a managing member of the Alliance, which provides funding and support for global collaborations to close the gap for people with progressive MS.