EMD Serono, Inc.
- Given orally, as one or two courses a year, depending on the study regimen.
- The FDA gave Fast Track approval status to cladribine in July 2010, and the drug may be available in the first quarter of 2011.
- This drug predominantly affects peripheral blood lymphocytes, with relative preservation of other cell types and components. It causes a preferential and sustained depletion of certain T cells in the immune system, as well as a decrease in B cells. (T and B cells are two types of lymphocytes, which help to keep the body free of infections and cancer.) Cladribine also seems to directly influence the overall T-cell response.
- In a large-scale Phase III clinical trial, cladribine significantly reduced relapse rates and other disease activity in people with relapsing-remitting MS.
- The two-year Phase III CLARITY trial of two levels of cladribine versus placebo involved 1,326 patients with RRMS. Each course consisted of once daily administration for four to five consecutive days, and study participants took cladribine for a total of eight to 20 days of treatment during the year. It met its primary endpoint, showing 55- to 58-percent reductions in annualized relapse rates, a 31- to 33-percent reduction in disability progression, and a substantial reduction in lesion burden. No clinical relapses were seen in 79 to 80 percent of the treated group, as compared to 61 percent in the placebo group. In the ongoing two-year extension study, all participants will receive cladribine; it will continue to assess safety, tolerability and effect on progression of disability.
- Detailed study data were released in the spring of 2010 at the American Academy of Neurology and Consortium of MS Centers meetings. Conclusions included that treatment with cladribine resulted in an early onset of effect in MRI and clinical outcomes. MRI evidence of disease activity was reduced by both cladribine regimens. The MRI findings were accompanied by significant improvements in clinical outcomes and a favorable safety profile. Additionally, a substantial proportion of patients achieved a disease activity-free status over 96 weeks.
- Its safety in pregnancy will be determined by the FDA in its final review.
- The long-term safety of cladribine will be tested in the eight-year PREMIERE registry. It will provide long-term active safety and risk-benefit information.
- Some patients with aggressive MS failed to respond clinically and by MRI after two short courses of cladribine. A reduction of T- or B-lymphocyte counts was not seen in these patients. It may be that some patients with aggressive MS disease are resistant to cladribine, may require additional courses to reduce relapses or MRI activity, or may require additional courses to cause a reduction of lymphocyte count which may be tied to the efficacy of the drug. A larger cohort of patients with aggressive MS is being followed to expand these findings.
- The ONWARD Phase II study of 200 individuals who have experienced at least one relapse while taking Rebif is now recruiting. This study combines oral cladribine with Rebif, to determine whether the combination is more effective than Rebif alone.
- The Phase III ORACLE MS study is ongoing, and will assess whether cladribine can delay the time to a second clinical demyelinating attack in 600 individuals who have had a first clinical demyelinating event (CIS). The study will be complete in October 2012.
- The main risk of a side effect with cladribine is the potential for developing infections, most commonly Herpes infections. A prolonged decrease in white blood cells has also been seen in some patients. The FDA will further evaluate other side effects and risks.