Post hoc analysis of the CLARITY study of Movectro (cladribine) in patients with relapsing remitting multiple sclerosis is published and shows a reduction in brain atrophy- Merck KGaA

Merck KGaA announced the publication of the results of a post hoc analysis of the Phase III CLARITY study of Movectro (cladribine) in multiple sclerosis. The analysis showed that cladribine reduced the annualised rate of brain volume loss - also known as brain atrophy - compared with placebo in patients with relapsing remitting multiple sclerosis. In addition, the analysis found that patients with lower rates of brain atrophy showed the highest probability of remaining free from disability progression at two years.

This data supports existing findings that increased brain volume loss over time is associated with worse clinical outcomes, such as increased disability progression and cognitive changes, in patients with multiple sclerosis. The CLARITY study primary (rate of relapse at 96 weeks) and key secondary endpoints (proportion of patients who were relapse free and the time to sustained progression of disability) were met. The brain atrophy analysis evaluated the effect of Cladribine tablets on brain volume loss (BVL) over 2 years in RMS and the association of BVL with confirmed disability progression in 1,025 (77.3%) of the patients in CLARITY.

The mean percentage brain volume loss per year was significantly reduced in patients treated with Cladribine Tablets 3.5 mg/kg (-0.56%�0.68, p=0.010, n=336) and 5.25 mg/kg (-0.57%�0.72, p=0.019, n=351) compared with patients treated with placebo (-0.70%�0.79, n=338). The risk of disability progression was also significantly lower in patients treated with Cladribine Tablets 3.5 mg/kg (HR 0.63, 95% CI 0.438, 0.894; p=0.010) and 5.25 mg/kg (HR 0.58, 95% CI 0.406, 0.833; p=0.003) than in those treated with placebo. After adjusting for treatment group, percentage brain volume loss per year showed a significant correlation with the cumulative probability of disability progression in the overall study population (HR 0.67, 95% CI 0.571, 0.787; p<0.0001). lymphopenia was the most commonly reported adverse event (ae) in patients treated with cladribine tablets. the incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators.>

See: "Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets" Nicola De Stefano et al. Multiple Sclerosis Journal First Published January 31, 2017 DOI: 10.1177/1352458517690269

Comment: Cladribine Tablets was denied approval in the US (2009) and EU (2010) for treatment of relapsing-remitting multiple sclerosis, as the regulatory agencies were concerned at safety issues with the drug and requested further trials. In July 2016 EMA accepted a new MAA which included data from three Phase III studies, CLARITY, CLARITY EXTENSION and ORACLE MS, and the Phase II ONWARD study. In these trials, Cladribine Tablets showed significantly reduced relapse rates, risk of disability progression and development of new MS lesions, as detected by MRI, versus placebo in patients with relapsing-remitting multiple sclerosis.