Results released from first multi-drug clinical trial in MS

• There is a pressing need to speed up the discovery of new treatments for progressive MS.
• The MS-SMART trial was a Phase 2 trial that tested three drugs, already used to treat other conditions, in in 445 people with secondary progressive MS.
• Unfortunately, the results showed that none of the three drugs tested have the potential to benefit people with progressive MS.
• This is the first time a clinical trial in MS has tested multiple drugs at the same time. This method delivers answers up to ten years earlier than a standard clinical trial.

There is a lack of treatment options for people with secondary progressive multiple sclerosis. Clinical trials are typically lengthy and expensive, but there is a pressing need to be able to assess greater numbers of potential treatments for progressive MS, and to do so more quickly. The MS-SMART trial, led by Professor Jeremy Chataway from University College London in the UK, aimed to address this.

What was the MS-SMART trial?

The MS-SMART trial is a Phase 2 trial that made use of an innovative ‘multi-arm’ design, which allows testing of three drugs at the same time. This type of trial design has been used to assess treatments for other types of disease, such as cancer, but was the first time that a multi-arm trial was attempted in progressive MS.

The trial tested three drugs in 445 people with secondary progressive MS. The three drugs are already used to treat other conditions. Amiloride is used to treat heart disease, fluoxetine is a medication for depression and riluzole is used for motor neurone disease. These drugs each target different processes in the body thought to contribute to progressive tissue damage and worsening (progression) in MS. They have all previously shown promising signs in the treatment of MS, based on experimental studies in the lab and early studies in humans, and were being tested for their ability to slow brain atrophy (shrinkage).

Participants took one of the drugs or a placebo pill (a dummy pill) for two years whilst participating in the trial. This took place under ‘blinded’ conditions (participants didn’t know which type of treatment they were taking) to ensure the results of the trial were not subject to bias.

What were the results?

Unfortunately, the results which were announced in October, showed that none of the therapies slowed brain atrophy. The outcome of the trial will still have impact for people with MS, because we now know that this type of trial design works – it is possible to test multiple drugs at the same time, speeding up assessment of potential therapies for progressive MS in the future.

The results also tell us a lot about the biological pathways in progressive MS. This will help researchers rule out and prioritise other drugs for future trials.

Dr Susan Kohlhaas, Director of Research at the MS Society which was one of the funders of this trial, says: “We know this is extremely disappointing for people with progressive MS and everyone involved with the trial.

“However, we’ve learned a huge amount from this study, which will increase our chances of future success. We’re now better placed to identify and rule out treatments that won’t work, and have demonstrated how to run faster, cheaper trials successfully – meaning we can test more potential drugs, quicker.”

Thank you to MS Research Australia for providing this article and to the UK MS Society for contributing to its contents.