EMD Serono Initiates Pivotal Phase III Program for Investigational Evobrutinib in Relapsing Multiple Sclerosis

EVOLUTION RMS 1 and 2 pivotal Phase III trials will investigate the efficacy and safety of evobrutinib in relapsing multiple sclerosis

– Evobrutinib is the first oral, highly selective Bruton’s Tyrosine Kinase inhibitor to show clinical proof of concept in relapsing multiple sclerosis

– Decision to initiate Phase III program based on effect seen with evobrutinib on magnetic resonance imaging endpoints at 24 weeks and annualized relapse rate over 48 weeks in Phase II

– Unique collaboration with Accelerated Cure Project for Multiple Sclerosis provided guidance on patient-reported outcomes measures and clinical study design

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EMD Serono 

Sep 10, 2019, 08:00 ET

ROCKLAND, Mass., Sept. 10, 2019 /PRNewswire/ — EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, 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 R&D for EMD Serono. “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, randomized, 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 annualized 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.

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