Merck KGaA initiates pivotal phase III programme for evobrutinib in relapsing multiple sclerosis.

Merck KGaA, a leading science and technology company, announced the initiation of two global pivotal Phase III trials (EVOLUTION RMS 1 and 2) studying the efficacy and safety of evobrutinib, an oral, highly selective Bruton�s Tyrosine Kinase (BTK) inhibitor in adult patients with relapsing multiple sclerosis (RMS).

�Evobrutinib is a potential innovation for people living with MS, as it may offer a novel dual mechanism of action that is thought to impact myeloid cells in addition to B-cells and thus could address MS pathobiology in a fundamentally new way,� said Luciano Rossetti, Head of Global Research & Development for the Biopharma business of Merck. �Evobrutinib, which was developed in our own laboratories, is an oral, highly selective BTK inhibitor that has shown clinical proof of concept in RMS. Progressing this molecule into Phase III is an important step for us and the MS community, with an opportunity to further advance on benefit-risk considerations for RMS patients.�

Evobrutinib is entering Phase III trials following the results of the Phase II clinical trial, which met its primary endpoint over 24 weeks of treatment, where the total cumulative number of T1 gadolinium-enhancing lesions was reduced with evobrutinib compared with placebo. The reduction of T1 gadolinium-enhancing lesions was observed at 12 weeks, the first time point at which MRI data was available, and maintained through 48 weeks with evobrutinib 75 mg QD and 75 mg BID. Further data show that the effect on relapse reduction observed at Week 24 was maintained through 48 weeks. In the Phase II trial, the most commonly observed adverse events of any grade associated with evobrutinib included nasopharyngitis and increases in levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipase. All events had an onset within 24 weeks of treatment initiation and were reversible on treatment discontinuation with no clinical consequences within the 52-week safety period. During the course of the study, 85 percent of patients (227 out of 267) completed 52 weeks of treatment.

EVOLUTION RMS 1 and 2 are multicenter, randomised, parallel group, double-blind, active-controlled studies comparing evobrutinib twice-daily with interferon beta-1a given intramuscularly once a week. The primary endpoint of both studies is annualised relapse rate (ARR) at Week 96. Secondary endpoints include time to first occurrence of 12- and 24-week confirmed Expanded Disability Status Scale (EDSS) Progression and total number of gadolinium-enhancing (Gd+) T1 lesions and new or enlarging T2 lesions assessed by magnetic resonance imaging.

Trial recruitment is currently underway with the goal of 1900 patients enrolled. The target completion is in June 2023.