New Late-Breaking Data at EAN Indicate Evobrutinib is the First BTK Inhibitor to Report Efficacy and Safety in MS Over 108 Weeks

• Investigational evobrutinib is the first and only Bruton's Tyrosine Kinase inhibitor to demonstrate high and sustained efficacy through 108 weeks in clinical studies
• No new safety signals identified in the 60 week open-label extension, consistent with data seen in more than 1,200 patients who have received evobrutinib to date, across MS and other conditions
• Late-breaking data presented as part of the European Academy of Neurology (EAN) Virtual Congress

ROCKLAND, Mass., May 23, 2020 /PRNewswire/ -- EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, today announced data on the long-term efficacy and safety profile of evobrutinib, an investigational, oral, highly selective Bruton's Tyrosine Kinase (BTK) inhibitor in adult patients with relapsing multiple sclerosis (RMS). The results from the Phase II open-label extension (OLE) study will be presented as a late-breaker at the European Academy of Neurology (EAN) 2020 Virtual Congress.

"These data demonstrate evobrutinib has a sustained and high impact on annualized relapse rate over 108 weeks," said Luciano Rossetti, Head of Global Research & Development for EMD Serono. "Greatest efficacy was clearly associated with BTK occupancy, and this further validates our choice of dose for the Phase III program. We are also encouraged by evobrutinib's breadth of consistent safety data, including no increase of serious infections in more than 1,200 patients up to two years."

Annual relapse rate (ARR) results in the double-blind phase of the study were maintained over the open-label extension, with patients receiving evobrutinib 75mg BID (twice a day) in the double-blind phase showing an ARR of 0.11 (95% CI 0.04–0.25) at week 48, and of 0.12 (0.06–0.22) for the 108-week period.

The data from the Phase II study continues to demonstrate that BID dosing can achieve higher efficacy than QD dosing on clinical outcomes, as demonstrated by reduced ARR. Modelling data show that greater than 95% BTK occupancy at trough is necessary in nearly all patients to achieve highest efficacy and this can be best achieved with BID dosing.

Data previously published in the New England Journal of Medicine reported the findings of the Phase II study where at 24 weeks, evobrutinib significantly reduced the cumulative number of T1 Gd-enhancing lesions compared to placebo, meeting its primary endpoint. At week 48, all patients could enter the OLE which assessed the long-term efficacy and safety of evobrutinib.

"The 108-week efficacy and safety data for evobrutinib through the double-blind and the OLE period are very robust," noted Dr. Xavier Montalban, Chairman & Director Neurology-Neuroimmunology Department & Neurorehabilitation Unit, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d'Hebron University Hospital, Barcelona, Spain. "This, combined with the high selectivity of evobrutinib, suggests that evobrutinib may offer a promising approach to MS treatment."

Of 267 randomized patients, 213 completed 108 weeks of treatment (48 weeks in main study and 60 weeks in OLE). Evobrutinib was generally well-tolerated, with the safety profile maintained during the OLE including no increase in infections and overall no new safety signals identified. Consistent with evobrutinib's high selectivity, patients participating in the trial experienced no systemic side effects, such as gastrointestinal disturbances. 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.

The transient elevated liver aminotransferases were restricted to the first 24 weeks following evobrutinib treatment initiation and were not observed in the OLE in patients continuing treatment with evobrutinib.

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. The two new trials, EVOLUTION RMS 1 and 2 are multi-center, randomised, parallel group, double-blind, double dummy, active-controlled studies of evobrutinib with teriflunomide, in participants with RMS. Each trial's primary endpoint is patients' ARR after 96 weeks of treatment. Secondary endpoints include the appearance of new or enlarging T2 lesions assessed by MRI scans and progressing disability as measured by the Expanded Disability Status Scale (EDSS).

About Evobrutinib
Evobrutinib (M2951) is in clinical development to investigate its potential as a treatment for multiple sclerosis (MS). 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 programme 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 1,500 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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