In the 2-year CLARITY trial (NCT00213135), 47% of patients treated with cladribine tablets (CT) (EMD Serono; Rockland, MA) achieved no evidence of disease activity (NEDA) compared with 17% of patients treated with placebo (P < .0001). of the dose of CT was 3.5 mg/kg in two oral courses of up to 10 days per year over 2 years and NEDA was defined as no relapses, no 6-month disability progression, and no T1 gadolinium-enhancing (Gd+) or active T2 lesions.
In the CLARITY extension study (NCT00641537), patients who had been treated with CT during CLARITY continued to receive CT or were switched to placebo. Those in both groups who had less than a 43-week gap in treatment continued to have similar rates of NEDA (46%-48%) (Table), suggesting durability of benefits beyond 2 years.
Additional analyses also compared efficacy of CT treatment for patients age 45 and under vs over 45. For subjects age 45 and under, those treated with CT had an annualized relapse rate (ARR) of 0.15 compared with 0.37 for those given placebo (P < .0001). For those over age 45 treated with CT the ARR was 0.14 vs .28 for those given placebo (P = .004).
Last, the analyses examined the rate of adverse events per 100 person-years, which were 3.88 in patients treated with CT vs 3.24 in those treated with placebo. Treatment-emergent adverse events that were higher in patients treated with CT vs placebo included serious lymphopenia (0.11 vs 0), serious infections and infestations (0.63 vs 0.44) driven primarily an increase in herpes zoster (0.05 vs 0), and neoplasms (0.65 vs 0.35).
Safety data was gathered from the CLARITY & CLARITY Extension studies, ORACLE-MS (NCT00725985), and the PREMIERE registry (NCT01013350). Across these studies, patients who received CT were mean age 37.8, 66.3% women, and balanced across groups in prior use of disease modifying treatment (DMT) vs placebo. No new major safety findings were identified in this latest integrated safety dataset, and no new safety signals were identified in the post-approval data shown.
John Walsh, MD, Vice President of Neurology & Immunology (N&I), US Medical Affairs for EMD Serono, Rockland, MA said, “These results reflect EMD Serono’s strong commitment to finding solutions for the MS community and giving patients multiple treatment options including Rebif, hopefully cladribine tablets, and potentially evobrutinib. We are pleased to see continued safety and efficacy data for cladribine tablets that further support the new drug application (NDA) that is currently under review by the FDA and hope to have a decision from the FDA in the first half of 2019.”