The trial results provide details of the effectiveness and safety of cladribine and fingolimod for relapsing remitting MS.

Results on cladribine

A two-year phase III clinical trial (called the CLARITY study) compared the effectiveness of cladribine in people with relapsing remitting MS and with that of a placebo treatment.

Results showed that cladribine reduced relapse rates (by 55-58%) and reduced the number of new brain lesions compared with a placebo treatment. Results also suggest that cladribine may reduce disability progression by up to 30% (as measured by Expanded Disability Status Scale over a period of three months). Long-term effects on disability progression are not clear from these study results.

There were some side effects associated with cladribine the most common serious side effect being lymphopenia (a reduction in white blood cells). This led to an increase in the likelihood of getting infections and a possible increased risk of cancer that will need to be looked at in the longer term.  

Results on fingolimod

Two phase III clinical trials (called the FREEDOMS and TRANSFORMS studies) were published side-by-side yesterday.

The FREEDOMS trial was a two year trial that involved 1033 people with relapsing remitting MS and compared the safety and effectiveness of fingolimod with a placebo treatment. The results of the trial showed that fingolimod (compared with a placebo treatment) reduced relapse rates by 54-60% and reduced the number of new brain lesions in people with MS. There appeared to be a 30% decrease in disability progression over 3 and 6 months, but long-term effects on disability progression are not clear from these study results.

The TRANSFORMS trial was a one year trial that involved 1153 people with relapsing remitting MS and compared the safety and effectiveness of fingolimod with that of beta-interferon-1a. The trial demonstrated that fingolimod can reduce relapse rates by 52% compared with beta-interferon and can reduce brain lesion activity. No effect on disability progression was observed in this trial.

Serious side effects of the drug included an increase in infections (with two fatalities associated with recurrent herpes virus infections, though it is not yet certain that this is fully attributable to the drug). There is also some evidence that fingolimod may increase the risk of non-fatal cancers, but this needs to be looked at in the longer-term.

Other side effects included temporary reductions in heart-rate and blood pressure associated with the first dose of fingolimod and macular oedema (degeneration in the eye). The serious side effects were associated with taking a high dose of fingolimod and Novartis have announced that they will be using a lower dose in future.  

Summary

Both drugs appear to be at least as effective, and potentially more effective, than some of the current drugs on the market for MS. Furthermore, taking a pill rather than having injections will be more convenient and less painful to many people with MS.

There are, however, new and potentially serious side effects associated with both of these drugs which will need to be considered by people who are thinking about taking them.
 

Outlook

Merck Serono, the makers of cladribine, applied for a license to market the pill in the UK in July 2009 and is currently awaiting a decision by the regulatory authorities.

Novartis, the makers of fingolimod, applied for a license to market the pill in the UK in December 2009 and is awaiting a decision by the regulatory authorities.

If successful, both drugs could be available as early as 2011, which could change the way MS is treated in the UK, giving people with MS more choice and, for the first time, the option to take a pill to help treat the condition.

Dr Doug Brown, Biomedical Research Manager at the MS Society, said: “This is great news for people with MS and signifies a shifting tide in the treatment of the condition.

“Availability of oral therapies will give people greater choice and being able to take a tablet instead of unpleasant injections will come as welcome relief.

“The evidence is now there and we will be working with the relevant authorities to make sure those who will benefit can get access.”
 

More information

For more information about these trials please read the MS Society research fact sheets on cladribine and fingolimod.

See previous news stories on cladribine and fingolimod.

The full articles can be found on www.nejm.org