Merck SeronoMerck Serono, a division of Merck KGaA, Darmstadt, Germany, announced that the Clarity1 phase-III pivotal trial of its proprietary oral formulation of cladribine (cladribine tablets) met the two-year primary endpoint of clinical relapse rate reduction in patients with relapsing-remitting multiple sclerosis (MS).

The two cladribine tablet treatment groups of the study, assessing different dose regimens, demonstrated a statistically significant reduction in the annualized rate of relapses compared to placebo. Patients from the lower total dose group experienced a 58 per cent relative reduction in annualized relapse rates with respect to placebo (0.14 versus 0.33 for the placebo group; p<0.001). Patients from the higher total dose group experienced a 55 per cent relative reduction in annualized relapse rates with respect to placebo (0.15 versus 0.33; p<0.001).

Overall, the frequencies of adverse events were low in the cladribine tablet treatment groups and were comparable to that observed in the placebo group. Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred more frequently in the cladribine tablet treatment groups. With the exception of lymphopenia, the most frequently reported adverse events in the three study groups were headaches and nasopharyngitis.

"We believe the CLARITY data mark an important milestone in the assessment of investigational oral treatments for multiple sclerosis and that cladribine tablets have the potential to make a real difference in the lives of patients," said Elmar Schnee, president of Merck Serono. "Based on the successful completion of the Clarity study, we plan to submit cladribine tablets for registration to the EMEA and to the FDA for mid-2009."

Secondary endpoints of the Clarity study were also met, including reduction of lesion activity as measured by magnetic resonance imaging (MRI), proportion of subjects relapse-free and disability progression. Full study results will be submitted for presentation at an upcoming scientific meeting.

The Clarity study was a two-year (96 weeks), randomized, double-blind, placebo controlled, international trial. It enrolled 1,326 patients with relapsing-remitting MS according to the revised McDonald criteria. Study participants were randomized to one of three different treatment groups consisting of two different dose regimens of cladribine tablets or matching placebo tablets (1:1:1 ratio). Cladribine tablets were given in two or four treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days, which means study patients took cladribine tablets for only 8 to 20 days during the year.

In the second year, two treatment courses were administered to all patient groups. The primary endpoint of the Clarity study was the qualifying relapse rate at 96 weeks. Secondary endpoints included MRI endpoints, proportion of subjects relapse-free and disability progression at 96 weeks. Out of the 1,326 randomized patients, 90 per cent of patients treated with cladribine tablets completed the study (92 per cent in the lower total dose group and 89 per cent in the higher total dose group) compared to 87 per cent in the placebo group.

Merck Serono's proprietary oral formulation of cladribine (cladribine tablets) is currently being evaluated in phase-III as a treatment for patients with relapsing forms of multiple sclerosis (MS).