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
- 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.