Cladribine

Parent company: Merck Serono, Inc.

The FDA gave Fast Track approval status to cladribine in July 2006. In March 2011, the FDA announced that it would not approve oral cladribine for MS without more safety information. In June 2011, Merck Serono announced that they will not currently pursue global approval for Cladribine Tablets for the treatment of RRMS, but would continue existing clinical trials. The company may consider a reapplication if safety concerns are lessened.

• Given orally, as one or two courses a year, depending on the study regimen.
  
  
• This drug predominantly affects peripheral blood lymphocytes (immune-system cells produced to fight infection and disease), 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.) Cladribine also seems to directly influence the overall T-cell response, which is believed to play a major role in the MS process.
  
  
• 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 patients 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 and 31-to-33-percent reductions in disability progression, as well as 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 are receiving cladribine; it will continue to assess safety, tolerability, and effect on progression of disability. Studies have shown a high compliance and study completion with few adverse event-related discontinuations.
  
  
• The long-term safety of cladribine is being tested in the eight-year PREMIERE registry, designed to provide long-term safety and risk-benefit information in approximately 1,500 patients who participated in other cladribine clinical trials. The study is scheduled for completion in 2018.
  
  
• The ONWARD Phase II study of 200 individuals who have experienced at least one relapse while taking Rebif is ongoing. This study combines oral cladribine with Rebif, to determine whether the combination is more effective than Rebif alone. It has an estimated completion date of November 2013.
  
  
• The Phase III ORACLE MS study is ongoing. It 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, also referred to as clinically isolated syndrome (CIS).
  
  
• The risk for adverse events with cladribine includes the potential for developing infections, with herpes being the most common. A prolonged decrease in white blood cells has also been seen in some patients.