Merck Highlights New Four-Year Efficacy and Safety Data for Investigational BTK Inhibitor, Evobrutinib, in RMS

• Data from the ongoing Phase II extension showed treatment benefits of evobrutinib were maintained over four years and remained consistent with the efficacy and safety profile seen in earlier data
• Evobrutinib is an investigational highly-selective, oral, CNS-penetrant BTK inhibitor with the potential to become a safe and highly efficacious treatment option for people living with RMS

DARMSTADT, Germany–(BUSINESS WIRE)–Not intended for UK and U.S. based media

Merck, a leading science and technology company, today announced updated long-term efficacy and safety data for investigational evobrutinib that continue to show a favorable safety and tolerability profile, consistent with what was seen earlier in the double-blind period (DBP) of the clinical trials. These data also continue to demonstrate its treatment benefit in reducing annualized relapse rates (ARR) over four years in people with relapsing multiple sclerosis (RMS). Data will be presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, taking place February 23-25.

Data from the ongoing Phase II open-label extension (OLE) trial of evobrutinib showed that treatment benefits were maintained over four years, with no new safety signals. Pooled ARR at week 228 of the OLE for all patients across the original DBP dosing groups was 0.13, with a further reduction seen in the period after switching from evobrutinib 75mg once-daily to 75mg twice-daily, from 0.19 to 0.10. For those receiving 75mg twice-daily dosing in the DBP, ARR was 0.11 at the end of DBP and 0.12 at week 228 of OLE. These data further support the twice-daily dosing currently being examined in Phase III clinical trials.

Overall, treatment emergent adverse events (TEAEs) were mild/moderate in the OLE, with 3.3% (n=7) of patients with RMS experiencing a serious TEAE. No new safety signals were seen in the OLE and evobrutinib continued to show consistent tolerability after up to four years of treatment. There was no dose dependent increase in TEAEs observed in patients who switched to twice-daily evobrutinib 75mg in the OLE.

“The MS community needs treatment options for both relapses and progression independent of relapse. This new long-term data complements previously presented data demonstrating evobrutinib’s impact on novel markers indicative of progression independent of relapse, such as slowly expanding lesions. Together, these data highlight evobrutinib’s potential to deliver a safe and highly efficacious option for people living with RMS,” said Jan Klatt, Senior Vice President, Head of Development Unit Neurology & Immunology at Merck. “We look forward to presenting detailed results from our fully enrolled Phase III clinical trials in the near future.”

Additionally, at ACTRIMS, data will be presented that includes analyses of the CLARIFY-MS study, showing the potential of MAVENCLAD^® (cladribine tablets) to improve outcomes in an impactful way for people living with RMS.

• Participants maintained their employment status over the two years of the study, which included the COVID-19 pandemic, with 43.4% (n=209) of patients employed full-time at month 24, compared to 47.5% (n=229) at baseline.
• Cognitive function remained stable over two years of treatment as measured at baseline, 12 and 24 months through the Brief International Cognitive Assessment for MS (BICAMS) battery, which is comprised of tests of mental processing speed and memory.

To keep up to date with our activities at ACTRIMS along with future data and information, please visit merckneurology.com/newsroom or follow us on Twitter @MerckHealthcare and LinkedIn: Healthcare Business of Merck

About Evobrutinib

Evobrutinib is an oral, CNS-penetrating, highly selective inhibitor of Bruton’s tyrosine kinase (BTK) in clinical development as a potential treatment for relapsing multiple sclerosis (RMS). It is the first BTK inhibitor to demonstrate clinical efficacy in the largest Phase II study with follow-up beyond three years as well as demonstrate an impact on early biomarkers of ongoing central inflammation that correlate with disease progression, including slowly expanding lesions (SEL) volume and levels of blood neurofilament light chain protein (NfL). Evobrutinib is designed to modulate B cell responses such as proliferation and antibody and cytokine release, as well as modulate macrophage/microglia activation. During Phase II, the BTKi dose finding study demonstrated that BID dosing achieved maximal efficacy with >95% BTK occupancy maintained in 98% of patients before the next dose. Evobrutinib is currently under clinical investigation and is not approved for any use anywhere in the world.

About the Open-Label Extension (OLE) Phase II Clinical Trial with Evobrutinib

In the 48 week double-blind period (DBP), patients with RMS were assigned to one of five treatment groups: placebo (switching to 25mg once-daily evobrutinib after 24 weeks), 25mg or 75mg once-daily evobrutinib, 75mg twice-daily evobrutinib, or open-label dimethyl fumarate (120mg twice daily for the first week and 240mg twice daily thereafter). At week 48, patients could enter the OLE and received evobrutinib 75mg once daily for a mean time of 49.8 weeks before switching to 75mg twice daily for the remainder of the OLE.

About MAVENCLAD^®

MAVENCLAD, approved by the U.S. Food and Drug Administration (FDA) on March 29, 2019, is the first and only short-course oral therapy for the treatment of adults with relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of multiple sclerosis (MS), and MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS). Patients should follow healthcare provider instructions including cancer screening, contraception and blood tests. The approved dose of MAVENCLAD is 3.5 mg per kg body weight over two years, administered as one treatment course of 1.75 mg per kg per year, each consisting of two treatment weeks. The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes. MAVENCLAD causes a dose-dependent reduction in lymphocyte counts followed by recovery.

Because cladribine is cytotoxic, special handling and disposal instructions should be followed.

MAVENCLAD has been approved in over 80 countries, including the European Union (EU), Canada, Australia and Switzerland, for various relapsing MS indications. Visit www.MAVENCLAD.com for more information.

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 has a pipeline focusing on discovering new therapies that have potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE), generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD).

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About Merck

Merck, a leading science and technology company, operates across life science, healthcare and electronics. Around 60,000 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 providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2021, Merck generated sales of € 19.7 billion in 66 countries.

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