Evobrutinib for multiple sclerosis
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What is evobrutinib for MS?
Evobrutinib, also called M2951, is an investigational oral treatment for relapsing forms of multiple sclerosis (MS), which includes relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).
The treatment, which is being developed by Merck KGaA (known as EMD Serono in the U.S. and Canada), is expected to slow or stop neurodegeneration in people with MS by reducing relapse rates and the number of active brain lesions.
Evobrutinib also is being studied as a potential treatment for other autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus.
Therapy snapshot
| Treatment name: | Evobrutinib |
| Administration: | Being tested in MS in oral tablet formulation |
| Clinical testing: | In Phase 3 trials for relapsing forms of MS |
How does evobrutinib work in MS?
MS is a neurodegenerative, autoimmune condition in which the immune system produces autoantibodies that mistakenly attack the myelin sheath that surrounds and protects nerve cells. This fatty sheath insulates nerve cells and facilitates their proper functioning. The breakdown of myelin, a process known as demyelination, results in brain lesions and leads to MS symptoms.
Immune cells such as T- and B-cells play an important role in driving inflammation and disease progression.
Bruton’s tyrosine kinase (BTK) is a protein present on several immune cells, including B-cells and macrophages, which are important in inflammation. BTK plays a vital role in B-cell activation, development, multiplication, and function. B-cells can activate T-cells and further promote the inflammatory process that damages the myelin sheath.
Evobrutinib is a BTK inhibitor. It blocks the BTK protein and prevents the activation and work of B-cells, to subsequently curb T-cell function and inflammation. By inhibiting the BTK protein, researchers hope that evobrutinib can reduce the nerve cell damage seen in MS patients and prevent disease relapses.
How will evobrutinib be administered in MS?
In a Phase 2 trial, evobrutinib was given as oral tablets at the following doses:
- 25 mg, once daily
- 75 mg, once or twice daily
Evobrutinib at 75 mg twice daily was shown to be the most effective and safe dose, and the dose associated with a lower annualized relapse rate compared with the other dosing regimens.
Evobrutinib in clinical trials
A placebo-controlled Phase 2 clinical trial (NCT02975349) compared the efficacy and safety of evobrutinib to that of Tecfidera (dimethyl fumarate), an oral MS treatment approved by the U.S. Food and Drug Administration (FDA) and marketed by Biogen.
Researchers randomly assigned 267 patients to Tecfidera, a placebo, or to three different doses of evobrutinib (25 mg once daily, 75 mg once daily, or 75 mg twice daily). Researchers reported no relapses after 48 weeks (almost a year) in 79% of patients given evobrutinib at its highest dose. The study also reported a significant reduction in the number of brain lesions in these patients after 24 weeks of treatment; this effect was maintained through 48 weeks of treatment.
Trial participants were invited to enroll in an extension study where all received evobrutinib at 75 mg twice daily. Patients showed a sustained reduction in relapse rates for up to two and 3 1/2 years.
Ongoing Phase 3 trials
Two ongoing and global Phase 3 studies — EVOLUTION RMS1 (NCT04338022) and EVOLUTION RMS2 (NCT04338061) — are comparing the safety and effectiveness of evobrutinib with that of Aubagio, marketed by Sanofi. Aubagio is an oral formulation of teriflunomide approved to treat MS.
Each study enrolled 930 adults, ages 18 to 55, with relapsing MS, for a total of 1,860 people. Participants are randomized to evobrutinib, taken twice daily, or Aubagio, once daily, for 96 weeks. Both studies’ primary goal is to measure changes in the annual relapse rate. Secondary goals include changes in disability progression and the formation of new or enlarging brain lesions.
The EVOLUTION trials are expected to finish in June 2026, with the release of top-line data possible in late 2023.
Common side effects of evobrutinib
In the Phase 2 trial, the most common side effects of evobrutinib’s use were:
- nasopharyngitis (more commonly known as a cold)
- increased blood levels of a liver enzyme called ALT, which may indicate liver damage (these values returned to normal when treatment was stopped)
Severe infections and unusually high levels of certain enzymes, indicative of pancreatic inflammation, also were found in a low proportion of patients.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about evobrutinib in MS
Evobrutinib inhibits Bruton’s tyrosine kinase (BTK), a protein involved in the development and maturation of immune cells, including B-cells. These cells play a major role in driving the inflammation that damages the nervous system in multiple sclerosis (MS). By inhibiting BTK, the investigational therapy may slow or even halt neurodegeneration in people with MS.
Evobrutinib has shown promising results in a Phase 2 trial. These findings supported the launch of two Phase 3 studies to confirm the therapy’s benefits in relapsing forms of multiple sclerosis. Top-line data from these trials are expected in late 2023 and both are estimated to finish in June 2026. However, it is too early to know if or when the therapy might be approved by the U.S. Food and Drug Administration.
It is not known whether the therapy is safe for use during pregnancy, as clinical trials of evobrutinib did not include pregnant or breastfeeding patients. In fact, among the trials’ criteria were that participants be neither pregnant nor breastfeeding, and/or lack child-bearing potential (defined as being post-menopausal or surgically sterile), or use effective contraception methods while on the study and at least two years after its completion. Patients should talk with their healthcare team if they become pregnant, plan to become pregnant, or are breastfeeding or plan to do so while on evobrutinib.
In clinical trials in MS patients, the earliest results of evobrutinib’s effects — a significant reduction in the number of brain lesions — were reported after about six months of treatment (24 weeks). The study also reported no relapses in 79% of patients treated for about one year (48 weeks) at the highest dose tested (75 mg, twice daily).
Neither hair loss nor weight gain have been reported as side effects of evobrutinib in multiple sclerosis clinical trials. However, in trials with another Bruton’s tyrosine kinase inhibitor, called tolebrutinib, hair loss was a reported side effect of the therapy’s use in a Phase 2 trial. Patients who experience unexpected effects after starting a new therapy should talk to their healthcare providers.
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