"EAST HANOVER, NJ, October 12, 2007- New preclinical data presented at European Committee for Treatment and Research of Multiple Sclerosis (ECTRIMS) in Prague suggests that FTY720 (fingolimod) directly reduces neurodegeneration and enhances repair of the central nervous system (CNS) damage caused by multiple sclerosis (MS) by interacting with sphingosine-1-phosphate receptors (S1P-R) expressed on brain cells. This mechanism of action may be in addition to the established anti-inflammatory role of FTY720 that is mediated by the reduction of inflammatory immune cells, called lymphocytes, from reaching the brain.
FTY720 is a novel, once-daily, oral treatment currently in worldwide Phase III clinical development to test its safety and efficacy as a disease modifying therapy for relapsing-remitting MS, which affects approximately 85% of people with multiple sclerosis.
The potential direct beneficial effect of FTY720 in the CNS is supported by the results of several preclinical experiments being presented at ECTRIMS, including research in animal models of MS and in vitro studies on CNS cells called oligodendrocytes.
In an animal model of MS (experimental autoimmune encephalomyelitis in rats), the administration of FTY720 directly into the CNS resulted in a statistically significant reduction in disease severity. This decrease in disease activity was seen in the absence of a reduction of lymphocytes in the bloodstream, suggesting that the favorable effect of FTY720 seen in this model is due to a direct effect in the CNS that is independent of the effects on peripheral lymphocytes.
In two experiments presented at ECTRIMS, the modulation of S1P-R by the addition of FTY720 resulted in an increase in the number, growth and survival of oligodendrocytes in cell culture. This effect of FTY720 on oligodendrocytes may help limit destruction of myelin and promote its repair and, thus, may contribute to the effectiveness of FTY720 in MS. Oligodendrocytes are cells in the CNS that make a fatty tissue, called myelin, which is necessary for normal signal transfer along nerve fibers in the CNS. Myelin and oligodendrocytes are typically damaged in MS.
"FTY720 crosses the blood-brain barrier and the drug's target - S1P receptors - are present on brain cells, including oligodendrocytes as shown in animal cell studies," said Jack Antel, Professor, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. "We are able to confirm that FTY720 directly modulates the S1P receptors on human oligodendrocyte progenitor cells."
FTY720 is currently being investigated in the largest worldwide Phase III clinical trial program to be conducted in MS to evaluate further its efficacy and safety as a disease modifying therapy for relapsing-remitting MS. This comprehensive program includes trials referred to as FREEDOMS, FREEDOMS II and TRANSFORMS. Recruitment is complete for FREEDOMS and TRANSFORMS. Recruitment is ongoing and on track for FREEDOMS II and FTY720 regulatory filing is planned for the second half of 2009. For more information about the clinical trial program, including eligibility criteria and location of U.S. study sites, patients can call the following toll-free number: 866-788-3930, or visit www.MSClinicalTrials.com.