Investigational MS Therapy Reduces Lesions, Relapse Rates in Phase 2 Study

Phase 2 data for evobrutinib shows reduction in lesions and relapse rates in patients with multiple sclerosis.

New data from the investigational multiple sclerosis (MS) drug evobrutinib showed that the therapy reduced lesions and decreased annual relapse rates in patients with relapsing MS, according to a phase 2 study.

Based on the analysis, evobrutinib is the first Bruton’s tryosine kinase (BTK) inhibitor to show clinical proof-of-concept in relapsing MS, according to a Merck press release. The 24-week data results were announced at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Berlin, Germany.

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The study included an open-label reference arm with dimethyl fumarate (240 mg BID), with no formal statistical comparisons between dimethyl fumarate and evobrutinib or placebo.

In the trial, 244 patients completed 24 weeks of treatment. Patients treated with evobrutinib 75 mg QD (once-daily) and 75 mg BID demonstrated a significant reduction in the number of gadolinium enhancing T1 (T1 Gd+) lesions measured at weeks 12, 16, 20, and 24, compared with patients receiving a placebo. According to the data, the mean total of T1 Gd+ lesions weeks 12 through 24 was 3.85 (5.44), 4.06 (8.02), 1.69 (4.69), and 1.15 (3.70) in the placebo, evobrutinib, and BID groups respectively. T1 Gd+ lesions per scan were significantly reduced with evobrutinib 75 mg QD and 75 mg BID, but not with 25 mg QD, according to the study.

Additionally, the study found that evobrutinib led to a clinically relevant decrease in annualized relapse rate (ARR). ARR reduction was seen with evobrutinib 75 mg QD (0.13; p=0.09) and 75-mg BID (0.08; p=0.06) versus placebo (0.37), according to the data. The secondary endpoint of the trial was also met, with new or enlarging T2 lesions per scan significantly reduced with evobrutinib 75 mg BID.

Overall, treatment with evobrutinib was well tolerated, with the most commonly reported adverse effects including increased ALT, AST, and lipase in the 75 mg BID group.

“The results of this study highlight the potential of BTK inhibitors as an oral disease-modifying treatment for relapsing MS,” Xavier Montalban, professor of medicine and department division director of neurology at the University of Toronto and director of the MS center at St. Michael’s Hospital, said in the release. “These findings suggest that the dual mechanism of action of evobrutinib, which impacts pathogenic adaptive and innate immune cells in multiple sclerosis, could translate into clinical efficacy.”

Reference

Positive late-breaking phase 2 data evaluating investigational oral therapy, evobrutinib in RMS [news release]. https://www.emdgroup.com/en/news/positive-late-breaking-phase-ii-12-10-2018.html. Accessed October 12, 2018.