Merck Initiates Pivotal Phase III Programme for Investigational Evobrutinib in Relapsing Multiple Sclerosis

DARMSTADT, Germany–(BUSINESS WIRE)–Merck, a leading science and technology company, today 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 (Gd+) lesions was reduced with evobrutinib compared with placebo. The reduction of T1 Gd+ lesions was observed at 12 weeks, the first time point at which magnetic resonance imaging (MRI) data was available, and maintained through 48 weeks with evobrutinib 75 mg QD (once a day) and 75 mg BID (twice a day). 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% 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 Gd+ T1 lesions and new or enlarging T2 lesions assessed by MRI.

As part of Merck’s commitment to patient-focused drug development, the company collaborated with the Accelerated Cure Project (ACP) for Multiple Sclerosis and its iConquerMS people-powered research network to capture and integrate the perspectives of people affected by MS into the design and implementation of the clinical trials. Through this innovative collaboration, a council of individuals living with MS provided feedback and insights on the choice of patient-reported outcomes (PROs) endpoints in the trials, specifically in relation to relevance of PRO measures to the real-world patient experience and insights on patient-facing materials. This engagement largely focused on the two PROs included as secondary endpoints: change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Physical Function (PF) and the PROMIS MS Fatigue Scores at 96 Weeks.

“Even with the most effective therapies for RMS, more than 50% of patients experience clinical or subclinical disease activity, therefore a need still exists for novel oral therapies that address MS pathobiology differently,” noted Dr. Xavier Montalban, Professor of Medicine and Department Division Director, Neurology, at the University of Toronto, Director of the MS Centre at St. Michael’s Hospital, Canada, Chairman & Director Neurology-Neuroimmunology Department & Neurorehabilitation Unit, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron University Hospital, Barcelona, Spain and principal investigator for the EVOLUTION RMS 2 trial. “We look forward to seeing the outcomes of this clinical programme following the promising Phase II results.”

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