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

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.

As part of the company's commitment to patient-focused drug development, EMD Serono 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 program following the promising Phase II results."

Trial recruitment is currently underway with the goal of 1,900 patients enrolled. The target completion is in June 2023.

About Evobrutinib
Evobrutinib (M2951) is in clinical development to investigate its potential as a treatment for multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is an oral, highly selective inhibitor of Bruton's tyrosine kinase (BTK) which is important in the development and functioning of various immune cells including B lymphocytes and macrophages. Evobrutinib is designed to inhibit primary B cell responses such as proliferation and antibody and cytokine release, without directly affecting T cells. BTK inhibition is thought to suppress autoantibody-producing cells, which preclinical research suggests may be therapeutically useful in certain autoimmune diseases. The global Phase III clinical development program evaluating evobrutinib in MS includes two pivotal studies, EVOLUTION RMS 1 and 2. Evobrutinib is currently under clinical investigation and not approved for any use anywhere in the world.

About Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory condition of the central nervous system and is the most common, non-traumatic, disabling neurological disease in young adults. It is estimated that approximately 2.3 million people have MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.

EMD Serono, Inc. and Multiple Sclerosis
For more than 20 years, EMD Serono has been relentlessly focused on understanding the journey people living with MS face in order to create a meaningful, positive experience for them and the broader MS community. However, there is still much that is unknown about this complex and unpredictable disease. EMD Serono is digging deeper to advance the science.

About EMD Serono, Inc.
EMD Serono - the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada - is engaged in the discovery, research and development of medicines for patients with difficult to treat diseases. The business is committed to transforming lives by developing and delivering meaningful solutions that help address the therapeutic and support needs of individual patients. Building on a proven legacy and deep expertise in neurology, fertility and endocrinology, EMD Serono is developing potential new oncology and immuno-oncology medicines while continuing to explore potential therapeutic options for diseases such as psoriasis, lupus and MS. Today, the business has approximately 1,300 employees around the country with commercial, clinical and research operations based in the company's home state of Massachusetts. www.emdserono.com

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