November 7, 2024 | News | Living with MS MS Research MS Symptoms MS Treatments

New MS therapies in development: ECTRIMS 2024

Part 2

Much of the buzz at this year’s meeting of the European Committee for Treatment and Research in MS (ECTRIMS) was about two new therapies in development for the treatment of MS.

Although there are nearly two dozen disease-modifying therapies (DMTs) to treat MS, there is still room for improvement in controlling the MS disease process. All of the current treatments reduce the inflammation that causes relapses and MRI lesions. But they all suffer from the same shortcomings: they have less impact on the neurodegenerative aspect of the disease that drives disability worsening, and limited efficacy for people with progressive forms of MS.

The two new treatments work differently, which may translate to better disease control. The following is a summary of the latest data.

Tolebrutinib: This is the second in a class of medications called BTK inhibitors, which inhibit an enzyme (called Bruton’s tyrosine kinase) that is found on some immune cells (B cells) as well as specialized cells in the brain (called microglia). Blocking BTK inhibits cell-to-cell signalling that promotes inflammation. This may result in less demyelination and nerve damage in the brain and spinal cord.

Three key tolebrutinib studies were presented at ECTRIMS. In the GEMINI I and II trials of people with relapsing MS, tolebrutinib was compared with Aubagio (Oh and colleagues. ECTRIMS 2024;O135). The trials were considered a failure although the final results were mixed. Tolebrutinib was no better than Aubagio in reducing relapses and was less effective in presenting new MRI lesions. However, tolebrutinib was substantially better than Aubagio in slowing disability worsening. One interpretation of these findings is that tolebrutinib is less effective than conventional treatments in reducing the inflammatory process that causes relapses and MRI lesions. However, it may be more effective in reducing the type of inflammation in the brain that is the main driver of disability. An earlier BTK inhibitor, evobrutinib, also failed its trial for the same reason and is no longer being developed. It is not known if tolebrutinib will be developed further for relapsing MS.

The third study, called HERCULES, looked at tolebrutinib in a subgroup of MS for which there are no current treatments – people with secondary-progressive MS (SPMS) who no longer have active disease (i.e. no relapses or new MRI lesions) (Fox and colleagues. ECTRIMS 2024;O136). At present, the only approved therapy for SPMS is Mayzent – but only if the SPMS is active (i.e. with relapses or new lesions). A total of 1,131 people received either tolebrutinib or a placebo. The people were older than in most trials (average age about 49 years) since SPMS generally develops only after years living with relapsing MS. Disability worsening was reduced by 31% with tolebrutinib. Treatment also reduced the number of new inflammatory lesions (although this study was supposed to include only those without inflammatory activity). Since tolebrutinib acts in the brain, it might have been expected to reduce the amount of tissue damage – but this was not seen, which raises further questions about how this treatment is acting in MS. The manufacturer is expected to ask health regulators for approval to market the drug as a treatment for non-active SPMS. Tolebrutinib may become available as early as next year.

Frexalimab: The second novel treatment in development is frexalimab, which targets a protein called CD40, which is involved in activating the immune response. A phase II trial showed that frexalimab reduced the number of inflammatory lesions in the brain over a three-month treatment period (Vermersch and colleagues. N Engl J Med 2024;390:589-600). That study has now been rolled out to 18 months (Giovannoni and colleagues. ECTRIMS 2024;O066). Over the longer term, frexalimab continued to suppress new lesions in the brain and spinal cord and appeared to be safe. These promising results may pave the way for the next phase of drug development, which will take several years to complete.

In part 3 of our ECTRIMS update we will look at interesting new research in MS.

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