Merck Unveils New MAVENCLAD

Merck Unveils New MAVENCLAD® Four-Year Data Highlighting Benefits of Early Treatment and Sustained Efficacy Across Multiple Measures of Disease Activity

• Phase IV studies      demonstrate the consistent safety and high efficacy of MAVENCLAD on      NEDA-3, MRI and cognition outcomes over four years

• New data on blood and CSF      biomarkers show the impact of MAVENCLAD to promote immune cell      reconstitution, while clinical data confirmed 93.7% of patients free from      PIRA

• MAVENCLAD has now treated      more than 100,000 patients globally, underscoring its trusted efficacy and      safety profile

DARMSTADT, Germany -- (BUSINESS WIRE) --

Not intended for UK-, US- or Canada-based media

Merck, a leading science and technology company, today announced presentations showcasing the long-term safety profile, sustained efficacy data, and durable effect of MAVENCLAD^® (cladribine tablets) in individuals with relapsing multiple sclerosis (RMS). Among 34 total MAVENCLAD presentations are data from several MAGNIFY-MS sub-studies demonstrating the impact of MAVENCLAD on disability progression, central inflammation, and an oral presentation on immune reconstitution effects. These data, along with six other company abstracts, will be presented at the 40^th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) taking place September 18-20 in Copenhagen.

“The efficacy of MAVENCLAD has long been established through traditional endpoints from our original pivotal trials and beyond. Now, with additional measures of the impact on neuroinflammation and progression, we can reaffirm and further solidify its long-term efficacy position within the MS treatment landscape,” said Alexander Kulla, Senior Vice President & Medical Unit Head Neurology & Immunology at Merck. “MAVENCLAD continues to demonstrate its consistent safety profile with sustained benefits, impacting the lives of more than 100,000 people living with MS."

Results from the MAGNIFY-MS extension, a Phase IV study evaluating patients (n=219) on MAVENCLAD with highly active RMS, confirmed 79.2% of patients achieved no evidence of disease activity (NEDA-3) during Year 4 of the treatment. The annualized relapse rate (ARR) remained low overall (0.09) and was further reduced (0.06) in treatment-naïve patients over four years. Similarly, the CLARIFY-MS extension showed the sustained benefits in MAVENCLAD-treated patients (n=280) on cognition, in addition to MRI outcomes and relapses, four years after the initial treatment dose. Specific to cognition, 77.5% of patients had improved or stable scores at four years, based on the 8-point cut-off of the Symbol Digit Modalities Test (SDMT). In both studies, safety data aligned with the established profile from clinical trials.

Two-year data from a MAGNIFY-MS sub-study found patients with highly active RMS treated with MAVENCLAD had low overall disability accrual, including low rates of progression independent of relapse activity (PIRA). At two years, rates for all disability measures were low overall with 93.7% of patients free from PIRA. The reduction of PIRA is especially notable in treatment-naïve patients (3.4% vs 8.5% in treatment-experienced patients), emphasizing the benefits of early treatment initiation with MAVENCLAD. Overall, these data suggest that MAVENCLAD is likely to preserve the physical abilities and prevent relapses in individuals with RMS, supporting the sustained efficacy and durable effect of MAVENCLAD.

Building on prior data, which showed MAVENCLAD reduces or eliminates oligoclonal bands in the cerebrospinal fluid (CSF), new two-year data demonstrate reductions in gene expression and protein levels of markers associated with inflammation, including pro-inflammatory cytokines, providing insights into the potential multifaceted effect of MAVENCLAD in the peripheral blood and CSF. This data suggests that immune reconstitution following treatment with cladribine tablets may shift the immune system to a less pathogenic state. Analyses of CSF proteomics and T and B cell transcriptomics further substantiate the clinical findings, suggesting the potential of MAVENCLAD to reduce disease activity and progression in RMS patients.

To view our 40 accepted abstracts and posters to be presented from across our MS portfolio at ECTRIMS, including innovative analyses of MAVENCLAD using artificial intelligence, please visit the Programme.

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.

More than 100,000 patients have been treated with MAVENCLAD since its launch in 2019. 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), cutaneous lupus erythematosus (CLE) and generalized myasthenia gravis (gMG).

About Merck

Merck, a leading science and technology company, operates across life science, healthcare and electronics. Around 63,000 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 2023, Merck generated sales of €21 billion in 65 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 MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics.

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