5:15 AM
Oct 12, 2018
 |  BC Extra  |  Clinical News

Phase II data for Merck's Btk inhibitor highlighted at ECTRIMS

Merck KGaA (Xetra:MRK) reported 24-week data from a Phase II trial to treat relapsing multiple sclerosis showing that evobrutinib (M2951) reduced the mean total number of gadolinium-enhancing T1 lesions by up to 2.7 over placebo. The compound is an oral Bruton's tyrosine kinase (Btk) inhibitor that Merck discovered in-house. Data were presented at the European Committee for Treatment and Research in Multiple Sclerosis meeting in Berlin.

Merck reported in March that evobrutinib met the primary endpoints in the trial of reducing the total number of gadolinium-enhancing T1 lesions from baseline to weeks 12, 16, 20 and 24 vs. placebo, but did not disclose details (see "Merck's Evobrutinib Meets in Phase IIb for MS").

The double-blind, international trial enrolled 267 patients with relapsing MS to receive placebo, one of three doses of evobrutinib or the active control Tecfidera dimethyl fumarate from Biogen Inc. (NASDAQ:BIIB). Merck said no formal statistical comparisons were conducted between the Tecfidera and evobrutinib/placebo arms, and the company did not disclose data for the Tecfidera arm.

At week 24, the mean total number of gadolinium-enhancing T1 lesions was 1.69 for once-daily 75 mg evobrutinib and 1.15 for twice-daily 75 mg evobrutinib vs. 3.85 for placebo (p=0.0015 and p=0.0313, respectively). The once-daily 25 mg dose of evobrutinib missed the endpoint (p=0.295).

On a secondary endpoint, evobrutinib led to an annualized relapse rate (ARR) of 0.13 at the once-daily 75 mg dose and 0.08 at the twice-daily 75 mg dose vs. 0.37 for placebo (p=0.09 and p=0.06, respectively). Merck said the ARR endpoint was not powered for significance.

Evobrutinib was well tolerated. The most common treatment-related adverse events included reversible and asymptomatic increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lipase levels in the twice-daily 75 mg dose arm.

Biogen markets Tecfidera, an oral activator of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; NRF2) pathway, to treat relapsing forms of MS. According to its U.S. label, the mean number of gadolinium-enhancing lesions at two years with Tecfidera was 0.1 compared with 1.8 for placebo in the Phase III DEFINE trial to treat relapsing-remitting MS (p<0.0001). Tecfidera led to an ARR of 0.172 vs. 0.364 for placebo in DEFINE (p<0.0001).

Sanofi (Euronext:SAN; NYSE:SNY) is also developing a Btk inhibitor to treat MS. SAR442168 (PRN2246) is in Phase I testing for the indication. The pharma has exclusive, worldwide rights to the compound from Principia Biopharma Inc. (NASDAQ:PRNB) under a 2017 deal.

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