Business Wire

Evobrutinib is the First and Only BTK Inhibitor to Demonstrate Reduction of a Key Biomarker of Neuronal Damage and Inflammation in Patients with MS

Share

Merck, a leading science and technology company, will present data from a Phase II placebo-controlled randomized trial at the 2021 American Academy of Neurology (AAN) Annual Meeting showing that the investigational Bruton’s tyrosine kinase (BTK) inhibitor evobrutinib significantly reduced blood neurofilament light chain (NfL) levels, a key biomarker of neuronal damage and inflammation, in patients with multiple sclerosis (MS). Elevated blood NfL levels have been shown to be associated with damage to neurons and inflammation and may predict future brain atrophy and disease progression.

“Blood NfL is a biomarker that may allow monitoring of disease activity and treatment response, which could be less burdensome and more sensitive than other standard clinical measures for MS patients,” said Prof. Jens Kuhle, MD, PhD, Head Multiple Sclerosis Centre, University Hospital Basel. “These data provide key insights into the role evobrutinib may play in modulating the clinical course of MS and further suggest that BTK inhibition with evobrutinib may reduce tissue damage associated with MS.”

A post-hoc analysis of the Phase II placebo-controlled trial of evobrutinib in patients with relapsing MS (RMS) evaluated 166 patients with NfL values at baseline and at least one post-baseline. The largest relative reductions of NfL levels were observed with evobrutinib 75mg twice daily (BID) at weeks 12 and 24 compared to placebo. Twice daily dosing with an exposure equivalent to 75mg twice daily is being carried through to the Phase III program which is on track to complete enrollment this year. Primary results from the Phase II study were previously published in the New England Journal of Medicine in 2019. As elevated NfL is associated with clinical disability and brain atrophy in MS, these results, combined with the previous clinical trial data that demonstrated a reduction in T1 Gd+ lesion and ARR, further support the hypothesis that BTK inhibition with evobrutinib may impact both inflammatory and progressive aspects of MS within the central nervous system (CNS).

Further supporting the impact of evobrutinib on CNS pathology in MS, a second oral presentation at AAN examined BTK and activated (phosphorylated) BTK (pBTK) levels in B cells isolated from RMS patients. pBTK was highly expressed in subsets of B cells of RMS patients, including T-bet and CXCR3 expressing memory B cells. Evobrutinib decreased CXCR3+ memory B cell transmigration through human CNS endothelial cell monolayers, suggesting evobrutinib may impact the activity of pathogenic B cells and modulate the progressive course of MS.

“Taken together, the presented pre-clinical and clinical data suggest that evobrutinib inhibits MS mechanisms involved in disease activity and progression,” said Danny Bar-Zohar, MD, Global Head of Development, Healthcare business of Merck. “Coupled with the already published and presented attributes of CNS penetration as well as very high BTK occupancy, these findings further substantiate the strong potential for evobrutinib to lead to a paradigm shift in the treatment of people living with MS.”

Separately, an exploratory analysis to be presented at the upcoming triMS.online conference on 27 May evaluated evobrutinib distribution into cerebrospinal fluid (CSF) relative to plasma concentration in patients with RMS. Plasma and CSF samples were collected from a subset of MS patients in the Phase II open-label extension (OLE) study receiving 75mg BID. Evobrutinib was detected in the CSF of all patients included in the analysis (n=9). CSF concentrations were generally consistent with free plasma concentrations. This suggests that evobrutinib, in addition to inhibiting BTK on peripheral cells, may also inhibit BTK-expressing B cells and myeloid cells in the CNS, which may impact MS disease progression.

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. 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 2.8 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.

Merck in Neurology and Immunology

Merck has a long-standing legacy in neurology and immunology, with significant R&D and commercial experience in multiple sclerosis (MS). The company`s current MS portfolio includes two products for the treatment of relapsing MS – Rebif® (interferon beta-1a) and MAVENCLAD® (cladribine tablets). Merck aims to improve the lives of patients by addressing areas of unmet medical needs. In addition to Merck`s commitment to MS, the company also have a pipeline focusing on discovering new therapies that have the potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE).

All Merck Press Releases are distributed by email at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

About Merck

Merck, a leading science and technology company, operates across healthcare, life science and electronics. Around 58,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From advancing gene-editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2020, Merck generated sales of € 17.5 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science and EMD Electronics.

To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.

Contact information

Tone Brauti Fritzen
tone-brauti.fritzen@merckgroup.com
+49 151 1454 2694

About Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

Moove secures USD $100 million Series B round19.3.2024 09:01:00 CET | Press release

Moove, the global mobility fintech that democratises access to vehicle ownership for mobility entrepreneurs, today announces that it has raised $100 million in a Series B funding round, valuing the company at $750m. Uber invested in the round alongside Mubadala, who led Moove’s previous funding round in 2023. The round will enable Moove to expand its customer focused revenue-based vehicle financing offering to 16 markets around the world by the end of 2025. A considerable portion of this expansion will focus on electric vehicles (EVs), which will lay the groundwork for a more sustainable and accessible mobility ecosystem for its customers worldwide. Ladi Delano, Founder of Moove,said: “Today’s announcement marks a significant milestone for us. When we founded Moove in 2020, we were motivated to solve the acute shortage of vehicle financing that over two million African mobility entrepreneurs faced. “This validation from Uber and others stands as a testament to the fact that what was on

Cielo Debuts First Generative AI for Talent Acquisition: CLO.ai19.3.2024 08:11:00 CET | Press release

Cielo, the world’s leading Talent Acquisition Partner, today debuts the first generative AI (GenAI) for talent acquisition: CLO.ai. Based on a new set of industry principles for responsible AI use, the intelligent tool allows talent leaders to maximize the power of GenAI for better hiring outcomes fast, while protecting candidates' experiences. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20240319387916/en/ “In a competitive, noisy market with many emerging, and sometimes unproven, methodologies and technologies, Cielo has established a responsible approach to artificial intelligence in human resources & talent acquisition. At Cielo, their data scientists, engineers, and talent acquisition experts collaborate to improve GenAI models, assess data for relevancy and accuracy, and operate in a secure environment, thus contributing to an enhanced experience for their clients and candidates. They are not only navigating the landsc

AMWC 2024: Galderma to Share New Data From Its Leading Injectable Aesthetic Portfolio19.3.2024 07:00:00 CET | Press release

Galderma will present the latest updates from its broad portfolio of clinically-proven and holistic range of aesthetic treatments at the 22nd Aesthetic & Anti-Aging Medicine World Congress (AMWC) on March 27-29, 2024. The diversity of Galderma’s portfolio, designed to meet the individual needs of healthcare professionals and patients, will be showcased in 16 research posters – including data from the world’s most diverse range of fillers (Restylane®), leading neuromodulator portfolio (RelabotulinumtoxinA, Alluzience® and Azzalure®) and original biostimulator (Sculptra®) – as well as two symposia and a booth, which will host an array of live demonstrations and ‘Meet the Expert’ sessions. “Galderma’s extensive activities at AMWC demonstrate our commitment to pushing the boundaries of injectable aesthetics, to anticipate and address tomorrow’s needs today. By evolving and expanding our existing treatments, developing new innovations, and conducting cutting-edge research into the groundbre

NetApp Empowers Customers to Securely “Talk to Their Data” in Collaboration with NVIDIA18.3.2024 23:00:00 CET | Press release

NetApp® (NASDAQ: NTAP) today announced it is collaborating with NVIDIA to advance retrieval-augmented generation (RAG) for generative AI applications. The new collaboration directly connects the just-announced NVIDIA NeMo Retriever microservices—coming to the NVIDIA AI Enterprise software platform for development and deployment of production-grade AI applications, including generative AI—to exabytes of data on NetApp’s intelligent data infrastructure. Every NetApp ONTAP® customer will now be able to seamlessly “talk to their data” to access proprietary business insights without having to compromise the security or privacy of their data. Enterprises want to leverage publicly available large language models to talk directly and securely to their corporate data with assurance that their private data will never be accessible outside the enterprise. Until now, enterprises that wanted to build internal chatbots, co-pilots, and applications that leverage corporate knowledge were faced with co

KPMG’s "Digital Gateway for Tax" Platform Raises Global Standards in Tax Functionality with Generative AI18.3.2024 18:38:00 CET | Press release

In a landmark move, KPMG has enhanced the capabilities of its Digital Gateway for Tax incorporating generative AI (genAI) as an independent component to communicate directly with data, enabling powerful insights and enhanced levels of efficiency. This pioneering Software as a Service (SaaS) is designed to provide an end-to-end solution for all members of the tax department and marks a significant milestone in tax technology, integrating generative AI for organizations embarking on their tax digital transformation journey. The KPMG Digital Gateway for Tax platform’s real strength lies in its content and transparent data enrichment capabilities. The solution empowers clients to use the Digital Gateway as their Centralized Knowledge Hub, where users can access company-specific documents through the unified genAI platform. The RAG approach (Retrieval Augmented Generation) is relied upon to effortlessly enrich models with additional content which helps ensure the information used to generat

HiddenA line styled icon from Orion Icon Library.Eye