More than 11,000 neurologists, investigators and trainees gathered in Seattle in late April for the 2009 annual meeting of the American Academy of Neurology, one of the most important venues for sharing clinical research progress related to multiple sclerosis and other neurological disorders. This year, there were over 400 platform and poster presentations focusing on progress related to MS. Presented in abundance at the meeting were short-term and long-term studies of the currently approved disease-modifying therapies for MS, which generally continue to show benefits and sometimes unsuspected mechanisms of action. But taking center stage at this year’s meeting were the first public presentations of positive results from two phase 3 clinical trials of experimental oral therapies for relapsing MS: cladribine and fingolimod.
DETAILS
Cladribine: Results from the CLARITY study of oral cladribine in 1326 people with relapsing-remitting MS were presented for the first time by Gavin Giovannoni, MBBCh, PhD (Queen Mary University London and Barts and The London NHS Trust). The study was sponsored by Merck Serono. Cladribine is a chemotherapy that kills immune T cells and B cells, both of which are thought to be involved in immune attacks in MS. After 96 weeks (nearly 2 years), the “annualized” relapse rate in those on cladribine was reduced by 54.5 to 57.5%, depending on the dose, compared to those on placebo. (For this primary endpoint of the study, those on placebo had an average of 0.33 relapses per year, versus 0.14 or 0.15 for those on therapy.). About 80% of those on cladribine were relapse-free over the two years, versus about 60% of those on placebo. Both doses of cladribine also produced significant reductions in disease activity detected with MRI, and reduced the risk of disease progression by about 32% relative to placebo. Data about the drug’s impact on loss of brain tissue (atrophy) has not yet been analyzed.
In terms of safety, Dr. Giovannoni 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 deficiency 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. A company press release suggested that they would apply for the drug’s marketing approval later in 2009. (Abstract LBS.001)
Fingolimod: Jeffrey Cohen, MD (Cleveland Clinic) presented first results of the Novartis-sponsored TRANSFORMS study that compared two different doses of oral fingolimod (FTY720) with Avonex® (interferon beta-1a, Biogen Idec) over only one year. The study randomly assigned 1292 people with relapsing-remitting MS who had experienced one or more relapses over the previous year (or two relapses in the previous two years) into one of three groups: Avonex, lower dose fingolimod, or higher dose fingolimod. Those taking the lower dose of fingolimod had 52% lower relapse rates after one year than those on Avonex, and 80 to 83% of those on either dose of fingolimod remained relapse-free over the year, compared to 69% of those on Avonex. The effect of fingolimod on longer term disability progression was not evaluated.
Adverse side effects seen more often in the treatment groups included temporary reductions in heart rate at the start of therapy, small increases in blood pressure, and a few cases of macular edema (swelling of the back of the eye). Two deaths from herpes infections occurred in the group taking the higher dose of fingolimod, and seven cases of localized skin cancer occurred in the fingolimod groups. Several longer phase 3 clinical trials are currently underway, including one involving people with primary progressive MS; these additional studies should help clarify whether the adverse events were related to the experimental treatment. A company press release suggested that they plan to apply for the drug’s marketing approval at the end of 2009. (Abstract S21.004)
With Information from the National MS Society
National Research and Programs
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