Multiple Sclerosis, New Data Confirm Cladribine’s Efficacy at 4 Years

New results confirm the long-term safety and sustained efficacy profile of cladribine tablets in people with relapsing multiple sclerosis (RMS). Among the 34 total presentations on cladribine tablets are data from several substudies of the Magnify-MS study demonstrating, at 4 years, the impact of treatment on disability progression and central inflammation and an oral presentation on the effects of immune reconstitution. These data, along with 6 other abstracts, are being presented by Merck at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which concludes today in Copenhagen.

“The efficacy of cladribine tablets has long been demonstrated through the achievement of traditional endpoints in pivotal studies,” said Alexander Kulla, M.D., Senior Vice President and Medical Unit Head, Neurology & Immunology, Merck. “Today, with additional measures of its impact on neuroinflammation and disease progression, we can reaffirm and further solidify its positioning as a treatment with long-term efficacy in the multiple sclerosis therapeutic landscape. Cladribine tablets continues to demonstrate a consistent safety profile and lasting benefits, impacting the lives of more than 100,000 people living with multiple sclerosis.”

Multiple sclerosis is a chronic, inflammatory disease of the central nervous system and is the most common non-traumatic, disabling neurological disorder in young adults.

Results from the extension of Magnify-Ms, a phase IV study evaluating patients (219) treated with cladribine tablets with highly active SMR – as stated in a note – confirmed that 79.2% of patients showed no evidence of disease activity (Neda-3) during the fourth year of treatment. The annualized relapse rate (ARR) remained low overall (0.09) and further decreased (0.06) in treatment-naïve patients, over 4 years. Similarly, the extension of the Clarify-Ms study showed sustained benefits in patients treated with cladribine tablets (280) on cognition, as well as on MRI outcomes and relapses, 4 years after the initial treatment dose. For cognition, 77.5% of patients achieved improved or stable scores at 4 years, based on the 8-point cut-off of the Symbol Digit Modalities Test (Sdmt). In both studies, safety data were consistent with those found in clinical trials.

Two-year data from a substudy of MAGNIFY-MS – the note continues – showed that treated patients with highly active MRS had an overall low rate of disability accumulation, including low rates of relapse-independent progression (PIRA). At 2 years, rates of all disability indicators were overall low, with 93.7% of patients free of PIRA. The reduction in PIRA was particularly evident in treatment-naïve patients (3.4% versus 8.5% in treatment-experienced patients), underscoring the benefits of early initiation of treatment with cladribine tablets. Overall, these data suggest that the drug is able to preserve physical capacity and prevent relapses in subjects with MRS, supporting the efficacy and long-lasting effect of the drug.

Building on previous data demonstrating that cladribine tablets reduces or eliminates oligoclonal bands in cerebrospinal fluid (CSF), new 2-year data demonstrate reductions in gene expression and levels of inflammation-associated markers, including pro-inflammatory cytokines, providing insight into the potential for a diverse effect in peripheral blood and CSF. These data suggest that the immune reconstitution mechanism following treatment may return the immune system to a less pathogenic state. CSF proteomics and T- and B-cell transcriptomics analyses further support the clinical findings, confirming the value of cladribine in reducing disease activity and progression in patients with MRS.