The investigational multiple sclerosis (MS) therapy cladribine tablets (Merck) has shown efficacy in reducing annualized rate of brain atrophy when compared to placebo in patients with relapsing remitting multiple sclerosis (RRMS).

The findings come from a post hoc analysis of the Phase 3 CLARITY study. The study was randomized, double-blind, placebo-controlled and lasted 2 years (96 weeks) including a total of 1,326 patients with RRMS. They were randomized (1:1:1) to receive either cladribine 3.5mg/kg, cladribine 5.25mg/kg or placebo. The primary endpoint was the relapse rate over 96 weeks; secondary endpoints included MRI endpoints, proportion of subjects relapse-free, and disability progression at 96 weeks. 

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Results showed that the mean percentage brain volume loss (BVL) per year was significantly reduced in those who were administered cladribine 3.5mg/kg (-0.56%±0.68; P=0.010; n=336) and 5.25mg/kg (-0.57%±0.72; P=0.019; n=351) vs. patients treated with placebo (-0.70%±0.79; n=338). These results corresponded with a significantly lower risk of disability in the cladribine-treated groups; 3.5mg/kg dose group (HR 0.63, 95% CI: 0.438, 0.894; P=0.010) and 5.25mg/kg dose group (HR 0.58, 95% CI: 0.406, 0.833; P=0.003) vs. those treated with placebo.

“This analysis is important because it confirms the link between reduced brain atrophy and reduced disability progression found in the CLARITY study,” said Nicola De Stefano, lead author and associate professor of neurology at the University of Siena. The findings support existing research which indicates that increased brain volume loss over time is associated with worse clinical outcomes, such as increased disability progression and cognitive changes, in MS patients.

Cladribine tablets are currently being evaluated in a clinical development program and are not yet approved for the treatment of any condition in the U.S. Speaking about the findings from the CLARITY study, Merck CMO Steven Hildemann said, “These findings […] further our resolve to make this investigational therapy available for patients living with relapse remitting multiple sclerosis.”

The full post hoc analysis is published in the Multiple Sclerosis Journal.

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