Clinical Efficacy of Cladribine Tablets in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS): Final Results from the 120-Week Phase IIIb Extension Trial to the CLARITY Study (P3.028)

Objective: To assess efficacy of cladribine tablets in RRMS patients treated for 2 additional years beyond an initial 2-year regimen (CLARITY). Background: Cladribine, given annually for 2years in short-duration courses in CLARITY, significantly improved clinical (relapses and disability progression) and MRI outcomes. After a variable treatment gap (median 40 weeks), 2 additional years of cladribine treatment vs. placebo were assessed in CLARITY-Extension (EXT). Methods: CLARITY, patients were randomized to treatment with placebo or cladribine (3.5 or 5.25mg/kg bodyweight). In CLARITY-EXT, placebo recipients in CLARITY received cladribine 3.5mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5mg/kg or placebo (5 groups total). This allowed comparison of 2 years-only treatment plus ≥2 years follow up vs. 4 years’ treatment. Clinical assessments included annualized relapse rate (ARR) and disability score. Results: Baseline characteristics were similar across groups, although placebo-recipients in CLARITY showed evidence of greater clinical and MRI-disease activity. In groups treated with cladribine in CLARITY, efficacy was maintained in CLARITY-EXT; 2 years’ additional-cladribine treatment was associated with a slight incremental benefit. The ARR in patients treated with cladribine 3.5mg/kg in CLARITY and placebo in was 0.15 (97.5[percnt]CI 0.09-0.21; n=98); in patients treated with cladribine 3.5mg/kg in both CLARITY and CLARITY-EXT, ARR was 0.10 (97.5[percnt]CI 0.06-0.13; n=186, P=0.059). Both groups showed comparable proportions of relapse-free patients (75.6[percnt] and 81.2[percnt], respectively) and times to first relapse (relative to first dose in CLARITY). Median EDSS scores were comparable across all groups; no significant between-group differences were seen in time to confirmed 3-month EDSS progression in CLARITY-EXT. Conclusions: CLARITY-EXT demonstrated that in a majority of patients, the clinical benefits (relapse and disability) of cladribine 3.5mg/kg given in Years 1 and 2 may be maintained for at least 4years, with decisions on further treatment based upon monitoring during this period.Study supported by: Merck KGaA, Germany. Disclosure: Dr. Giovannoni has received personal compensation for activities with AbbVie Biotherapeutics Inc., Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis, Teva, Ironwood, and Novartis. Dr. Comi has received personal compensation for activities with Teva, Novartis, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Almirall, and Serono Symposia International Foundation. Dr. Cook has received personal compensation for activities with Merck Serono, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc. Dr. Rammohan has received personal compensation for activities with EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme Corporation, Novartis, Teva Neurosciences, Acorda and Roche/Genentech Inc. as a speaker and committee member. Dr. Soelberg-Sorensen has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Genmab, Teva, Elan, and GlaxoSmithKline, Inc. Dr. Vermersch has received personal compensation for activities with Biogen Idec, Sanofi, Bayer, Novartis, Merck Serono, GlaxoSmithKline, and Almirall. Dr. Vermersch has received research support from Biogen Idec, Sanofi, Bayer, and Merck Serono. Dr. Martin has received personal compensation for activities with EMD Serono, Inc. as an employee. Dr. Dangond has received personal compensation for activities with EMD Serono, Inc. as an employee. Dr. Dangond received personal compensation for activities from EMD Serono, Inc., a subsidiary of Merck KGaA, Massachusetts, USA as an employee.