Merck announced compelling four-year data demonstrating the sustained efficacy of MAVENCLAD® (cladribine tablets) in treating relapsing multiple sclerosis (RMS), with nearly 9 in 10 patients remaining free from progression independent of relapse activity. The findings, presented at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, reinforce the drug's position as a transformative therapy in the MS treatment landscape.
Robust Long-Term Efficacy Data
An integrated analysis of four-year data from two major Phase 4 studies, CLARIFY-MS (n=482) and MAGNIFY-MS (n=270), revealed remarkable durability in treatment outcomes. At Year 4, 83.4% of patients were free from confirmed disability progression (CDP) and 89.2% were free from progression independent of relapse activity (PIRA). Additionally, 15.4% of patients experienced confirmed disability improvement.
The data showed particularly promising results for younger patients, with those aged ≤40 experiencing significantly lower rates of PIRA compared to those over 40 (7.6% vs. 15.4%, respectively). This finding underscores the importance of early intervention in MS treatment.
"As the only high-efficacy short-course oral treatment, MAVENCLAD has demonstrated sustained benefits across a variety of outcomes—extending beyond relapses and MRI—without requiring continuous immunosuppression," said Alex Kulla, Senior Vice President & Global Head of the Neurology & Immunology Medical Unit for the Healthcare business of Merck.
Neuroinflammation and Brain Volume Preservation
Data from MAGNIFY-MS provided crucial insights into MAVENCLAD's broader central nervous system benefits. At Year 2, the treatment demonstrated significant reductions in key biomarkers of neuroinflammation, including serum glial fibrillary acidic protein (GFAP), immunoglobulin G (IgG) index, and C-X-C motif chemokine ligand 13 (CXCL-13) levels in both serum and cerebrospinal fluid.
Brain imaging data revealed that the brain atrophy rate in MAVENCLAD-treated patients was comparable to that observed in healthy populations. From Years 2 to 4, annualized percent brain volume change remained below 0.4% across all subgroups. Patients with low brain atrophy rates at Year 4 showed markedly lower annualized relapse rates (0.04 ±0.12 vs. 0.16 ±0.26) and less clinical deterioration compared to those with higher brain volume loss.
Treatment Profile and Mechanism
MAVENCLAD, approved by the U.S. Food and Drug Administration on March 29, 2019, represents the first and only short-course oral therapy for treating adults with relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). The approved dose 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 involves cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in lymphocyte depletion. This approach causes a dose-dependent reduction in lymphocyte counts followed by recovery, providing durable efficacy without requiring continuous immunosuppression.
Real-World Impact and Safety Profile
Since its launch in 2019, more than 130,000 patients have been treated with MAVENCLAD, accumulating over 360,000 patient-years of exposure. The drug has been approved in over 80 countries, including the European Union, Canada, Australia, and Switzerland, for various relapsing MS indications.
Due to its safety profile, MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate MS treatments. The therapy is not recommended for patients with clinically isolated syndrome (CIS) and requires careful monitoring including cancer screening, contraception guidance, and regular blood tests.
Multiple Sclerosis Disease Burden
Multiple sclerosis affects approximately 2.9 million people worldwide and represents the most common non-traumatic, disabling neurological disease in young adults. The chronic, inflammatory condition of the central nervous system presents with varied symptoms, with the most common including blurred vision, numbness or tingling in the limbs, and problems with strength and coordination. Relapsing forms of MS are the most prevalent.
The comprehensive ECTRIMS 2025 data presentation includes over 30 abstracts from Merck's MS portfolio, with additional studies examining treatment continuation beyond four years, malignancy incidence rates, and clinical outcomes in aging patients. These findings collectively support MAVENCLAD's role in delivering durable, effective care for individuals with RMS from early diagnosis through later stages of life.
