Cladribine

Cladribine is an experimental new drug treatment for people with relapsing remitting multiple sclerosis (MS) that is taken by mouth.

Other names: Leustat
In development for: Relapsing remitting MS
Status: Phase III, applied to US and European regulators for license December 2009
Last updated: June 2010

How does it work?

Cladribine is currently licensed to treat certain forms of leukaemia. It apears to kill off certain immune cells (lymphocytes) that are involved in the autoimmune destruction of myelin. By reducing the number of destructive immune cells in circulation, it is thought it may slow down or stop this autoimmune attack.

How is it given?

As a cancer treatment, cladribine is an intravenous infusion.

In the current trials as a treatment for relapsing remitting MS, cladribine is taken orally as tablets.

Clinical studies

Although previous trials of injectable cladribine in people with MS have not shown a change in relapse rate or progression of disability, new trials of oral cladribine are underway.

CLARITY

Cladribine has been evaluated in a two year phase III study, known as CLARITY (CLAdRIbine Tablets treating MS orallY), involving more than 1300 people with relapsing remitting MS.

Two different dosing routines were compared to placebo: cladribine was taken once daily for five consecutive days, either twice a year for the two years (low dose) or four times in the first year and twice in the second year (high dose).

Those in the low dose group experienced a 58% reduction in annual relapse rate compared to placebo, while those in the high dose group experienced a 55% reduction. Other clinical measures showed similar results.
Read abstract.

Further clinical trials

CLARITY extension study

This extension study is designed to provide data on the long-term safety and effectiveness of cladribine tablets for up to four years,. People in the placebo group of the original CLARITY study will take cladribine tablets while people in the two cladribine treatment groups will be allocated 2:1 to receive either cladribine or placebo. Further details of this study.

ORACLE MS (Oral cladribine in early MS)

Recruitment is underway for this two-year phase III placebo-controlled trial to evaluate the effectiveness and safety of cladribine tablets as a single therapy in patients at risk of developing MS (people who have experienced their first symptoms suggestive of MS). The main measure of this study will be the time taken a formal, clinical diagnosis of MS. Further details of this study.

ONWARD (Cladribine add-on to Inteferon-Beta (IFN-b) therapy in MS subjects with active disease)

Recruitment is underway for this phase II placebo-controlled trial which is designed to evaluate the safety and tolerability of cladribine as an add-on therapy to people with relapsing forms of MS who continue to show signs of active disease while on established interferon-beta therapy. Further details of this study.

PREMIERE (Prospective observational long-term safety registry of multiple sclerosis patients who have participated in cladribine clinical trials)

People who have taken part in a clinical trial for oral cladribine are invited to be monitored for long-term safety issues. Further details of this study.

Side effects and contraindications

Researchers presenting data for the CLARITY study at the 2009 American Academy of Neurology meeting reported that 8.7% of those on cladribine experienced serious adverse events, versus 6.4% of those on placebo. There were 5 cases of different types of cancer among the 889 people who were on active therapy, and one of the main side effects experienced by those on active therapy was abnormally low levels of white blood cells (lymphopenia), which might be expected from this type of agent and which would probably require monitoring if the drug becomes an approved therapy. After lymphopenia, headaches and nasopharyngitis (inflammation of the nasal passsages and upper part of the throat) were the next most frequently reported side effects in all three groups.

Latest update on licensing

The manufacturers, Merck Serono, submitted the drug for licensing in 2009. The National Institute for Health and Clinical Excellence (NICE) intends to appraise cladribine through its Single Technology Appraisal (STA) process and has already drawn up a draft scope for the appraisal.

References

Brousil JA, et al.
Cladribine: an investigational immunomodulatory agent for multiple sclerosis.
Annals of Pharmacotherapy 2006;40(10):1814-1821
Read abstract

Giovannoni G, et al.
A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis
New England Journal of Medicine 2010;362(5):416-426.
Read abstract.

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