Efficacy of cladribine tablets in multiple sclerosis
Clinical trial results have shown that cladribine tablets can be an effective treatment for highly active, relapsing forms of multiple sclerosis, with significant clinical benefits in relapse rate, disability progression, and radiological measures. Compared with placebo, patients who received cladribine tablets (3.5 mg/kg) in the CLARITY study had a 58% reduction in annualized relapse rate and 47% of patients showed no evidence of disease activity at 2 years. Clinical improvements can be observed at Week 24 of treatment, and benefits may be sustained up to 4 years, beyond the 2-year dosing period and recovery of total lymphocytes. Post-hoc analyses of clinical trial data showed that 89% of patients remained free from disability progression two years after treatment.Further analyses of a subgroup of patients in the CLARITY study who had very active multiple sclerosis showed a 67% reduction in relapse rates and an 82% reduction in disability progression in those treated with cladribine tablets. Similarly, clinical improvements were seen in lesion burden on MRI scans in this population.Studies evaluating the treatment effects of cladribine tablets across a spectrum of baseline demographics and disease characteristics showed that the relative risk of relapse was significantly reduced compared with placebo, irrespective of previous treatment experience.Furthermore, treatment with cladribine tablets has been shown to significantly reduce the rate of brain atrophy in patients with highly active relapsing-remitting multiple sclerosis.
A meta-analysis of data from clinical trials comparing the risk of cancer and other disease-modifying therapies showed that cladribine tablets did not increase the risk of cancer at the doses used in the initial clinical trials.Based on the supporting data from the completed clinical trials that confirmed no increased risk of cancer, Merck announced it would again seek regulatory approval. In 2016, the EMA accepted its application for review. On June 22, 2017, the EMAs Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the treatment of relapsing forms of multiple sclerosis.Cladribine tablets were later approved in Europe, in August 2017, for highly active relapsing-remitting multiple sclerosis, and has since been approved by the FDA for the treatment of relapsing-remitting and secondary progressive multiple sclerosis in the US. Use in multiple sclerosis
As per the EU label, cladribine tablets are indicated for the treatment of adult patients with highly active relapsing multiple sclerosis as defined by clinical or imaging features: (i) patients with a relapse in the previous year and at least one T1 Gd+ lesion or 9 or more T2 lesions, while on another disease-modifying therapies or (ii) patients with two or more relapses in the previous year, whether on disease-modifying treatment or not.Two main approaches to multiple sclerosis treatment maintenance therapy are used – immunomodulation and immunosuppression and alternatively, immune reconstitution therapy. Classified as the latter, cladribine tablets are administered intermittently as a short treatment course without continuous immunosuppression.