Evobrutinib (M2951)

Experimental Medications: New S1P Receptor Modulators

Company: Merck

  • Oral medication being studied at 25 mg daily, 75 mg daily, and 75 mg twice daily
  • Being studied in RMS and SPMS

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B cells, which help the body fight infection, have become an increasingly prominent focus of MS research. That’s because when B cells become overabundant, they activate the T lymphocytes (T cells) known to cause the central nervous system inflammation that damages brain cells and their protective fiber (myelin) in MS. Bruton’s tyrosine kinase (BTK) inhibitors, currently approved to treat certain B-cell cancers, impede B-cell proliferation by blocking an enzyme that contributes to B-cell development.75

Evobrutinib is a BTK inhibitor under development for relapsing and secondaryprogressive forms of MS (RMS and SPMS). This investigational medication demonstrated efficacy in a recent 48-week, Phase II, doubleblind trial. A total of 243 participants with RMS or SPMS were assigned to one of five arms for the first 24 weeks of the study: evobrutinib 25 mg daily, 75 mg daily, or 75 mg twice daily; open-label dimethyl fumarate (Tecfidera®) 240 mg twice daily; or placebo.

At 24 weeks, the average total number of T1-enhancing lesions on MRI was significantly lower among patients in the groups receiving 75 mg of evobrutinib daily or twice daily (1.69 with daily dosing and 1.39 with twice-daily dosing) than among participants receiving placebo (4.07). Relapse rates were also lower among individuals who received evobrutinib 75 mg once or twice daily compared with placebo, but the difference was not statistically significant. Asymptomatic liver enzyme elevations were reported with evobrutinib 75 mg twice daily, but were considerably less common in other groups.76

Upon completing the trial’s first 24-week period, participants then entered the second 24-week phase, during which patients in the placebo group were switched to evobrutinib 25 mg once daily. In all, 227 subjects completed both 24-week phases of the 48-week trial.

During the second study phase, T1-enhancing lesions still were significantly less common among both the evobrutinib 75 mg daily and 75 mg twice daily treatment groups at weeks 12, 16, 20, and 24, compared with the original placebo group now receiving 25 mg of evobrutinib daily. Researchers said that these findings suggest that evobrutinib may be effective as a long-term disease-modifying therapy.76

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