Emerging new treatmentsFriday, September 30, 2005, 14:45 - 15:00
Promising results with a novel oral immunomodulator - FTY720 - in relapsing multiple sclerosisL. Kappos, E.-W. RadŁ, J. Antel, G. Comi, X. Montalban, P.W. O'Connor, C. Polman, O. Bettoni-Ristic, T. Haas, R. Preiss, A. Korn for the FTY720D2201 Study Group
Background: FTY720,the first oral sphingosine-1-phosphate receptor modulator, induces rapid and reversible sequestration of lymphocytes in secondary lymphoid organs(SLO), thereby preventing their migration to sites of inflammation without affecting induction or expansion of lymphocyte responses in SLO.
Methods: In this international, multicenter, double-blind study 281 patients were randomized 1:1:1 to Placebo (PL), 1.25mg or 5.0mg FTY720 orally qd for 6 months, followed by extension to 1 year with PL patients re-randomized to receive dose-blinded FTY720. We report results of the PL-controlled phase. Patients had monthly MRI scans and 3-monthly neurological evaluations.
Results: A marked reduction in total number of Gadolinium(Gd)-lesions (primary outcome, p<0.001 for FTY720 1.25mg, p=0.006 for FTY720 5mg), as well as volume of Gd-lesions (p=0.002 for FTY720 1.25mg, p=0.009 for FTY720 5mg) and number of T2 lesions (p<0.001 for both doses) was observed for both FTY720 groups vs PL. Benefits were first seen after 2 months and continued to increase. After 6months, 77% patients in the FTY720 1.25mg group and 82% in the 5mg group were free of Gd-lesions vs 46.9% in PL (p<0.001 for both doses). Relapse rate was reduced by 55% in FTY720 1.25mg(p<0.009) and by 53% in the 5mg group (p<0.014) vs PL. Proportion relapse-free patients (86% in both FTY720 groups vs 70% in placebo, p=0.007 for FTY720 1.25mg, p=0.008 for FTY720 5mg) and time to first relapse (p=0.007 for FTY720 1.25mg, p=0.012 for FTY720 5mg) increased in both FTY720 groups vs PL. Half the number of patients required steroids with FTY720(12% and 11% for 1.25mg and 5mg) as compared to PL (25%) and more relapses achieved complete recovery in FTY720 1.25mg (75%) as opposed to PL (36%), suggesting that relapses were less severe in FTY720 treated patients. Treatment was generally well tolerated with 255 (91%) of patients completing study, of whom 98% elected to continue into the extension phase. Adverse events appeared to be dose-related, the profile for FTY720 1.25mg being generally similar to PL. Most frequently reported adverse events were mild headaches and nasopharyngitis (>15% patients).
Conclusion: FTY720 administered orally once daily over 6 months led to significant reductions in MRI and clinical disease activity at both doses evaluated. If these promising data are confirmed in Phase 3, FTY720 might represent a new potent therapeutic option in MS with the additional benefit of oral administration.