Novartis oral MS therapy FTY720 shows reduced risk of confirmed disability progression
Combined data from TRANSFORMS and FREEDOMS studies show significant efficacy in reducing relapses, disability progression and MRI lesions in MS
Results of the TRANSFORMS] and FREEDOMS studies, the two pivotal Phase III clinical trials with oral FTY720 (fingolimod), have been published in The New England Journal of medicine, providing comprehensive evidence to support the efficacy and safety profile of this first-in-class therapy for multiple sclerosis (MS).
The data, from one of the largest Phase III programs conducted in MS, were included in the applications for regulatory approval submitted to the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) in December 2009. In both studies, two doses of FTY720 were examined (0.5 mg and 1.25 mg). Approval is sought for the lower 0.5 mg dose as the results from the studies indicate that this dose has the most positive benefit-risk profile.
The one-year TRANSFORMS study involving 1,292 patients showed that oral FTY720 0.5 mg reduced relapses by 52% compared to interferon beta-1a (Avonex®) given by intramuscular injection, while the reduction with FTY720 1.25 mg was 38% (both p<0.001). The two-year FREEDOMS study, involving 1,272 patients, showed that FTY720 reduced the relapse rate by 54% for the 0.5 mg dose and 60% for the 1.25 mg dose compared to placebo (both p<0.001). Patients on FTY720 0.5 mg also had a 30% lower risk of disability progression, three-month confirmed (p=0.02) and a 37% lower risk of disability progression, six-month confirmed (p=0.01) over two years compared to placebo. Similarly, the FTY720 1.25 mg dose reduced the risk of three-month and six-month confirmed disability progression by 32% (p=0.02) and 40% (p=0.006) respectively.
In both studies, treatment with FTY720 also resulted in statistically significant reductions in brain lesion activity and reduced loss of brain volume as measured by magnetic resonance imaging (MRI).
FTY720 has the potential to be the first approved therapy in a new class of drugs called sphingosine 1-phosphate (S1P) receptor modulators. These medicines reduce inflammation and may also have a direct beneficial effect on cells in the central nervous system (CNS). FTY720 acts selectively by retaining certain lymphocytes (a sub-group of white blood cells) in the lymph nodes, reducing the number of lymphocytes that reach the brain where they can cause inflammatory destruction. This lymphocyte retention is reversible, allowing circulating lymphocytes to regain normal levels if treatment is stopped.
The completed MS FTY720 studies and their extensions include more than 2,300 patients with approximately 4,000 patient-years of exposure, including some patients now in their sixth year of treatment. Safety is also being monitored in approximately 1,000 additional patients in ongoing MS studies.
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