Late breaking newsSaturday, October 01, 2005, 09:45 - 10:00
Phase II study with oral FTY720 in relapsing MS: results of the dose-blinded active drug extension phase at 12 monthsP. O’Connor, J. Antel, G. Comi, X. Montalban, E.W. Radü, T. Haas, A. de Vera, G. Karlsson, L. Kappos (Toronto, Montreal, CAN; Milan, I; Barcelona, E; Basle, CH)
Background: FTY720, the first oral sphingosine-1-phosphate receptor modulator, has demonstrated pronounced effects on both MRI and clinical disease activity in a 6-month, double-blind, multicenter, placebo-controlled study in 281 patients with relapsing MS.
Goal: To report the results of the ongoing, dose-blinded, active drug extension study at 12 months.
Methods: In the initial placebo-controlled part of this study, 281 patients were randomized 1:1:1 to receive placebo (Group PL), 1.25mg (Group A) or 5.0mg (Group B) FTY720 orally qd during Months 0-6. After 6 months, patients in Groups A & B continued on their blinded FTY720 treatment assignment while patients in Group PL were re-randomized to receive either FTY720 1.25mg (Group PL-A) or 5mg (Group PL-B) blinded during Months 7-12.
Results: 250 patients entered the extension phase and 227 (91%) completed 12 months on study drug. In the 12-month-Extension-ITT analysis, Groups A (n=87) and B (n=80) had an annualized relapse rate of 0.36/0.28 and 0.32/0.23 in Months 0-6 (PL-controlled)/and Months 7-12 (dose-blinded), respectively. In Groups PL-A (n=40) and PL-B (n=43) the annualized relapse rates during months 7-12 were reduced by >50% compared to Months 0-6. In the 12-month ITT analysis, the percentages of patients relapse-free during 12 months were for Group A 80.0% (n=94) and for Group B 83.8% (n=94). At the month 12 MRI, 84.3% of patients in Group A and 89.1% in Group B were free from Gd-enhanced lesions. The number of Gd-enhanced lesions remained at low levels in Groups A and B while it had clearly decreased as compared to Month 6 in Groups PL-A and PL-B (p<=0.001). The median total number of new T2 lesions over 12 months was 1.0 for both Groups A and B. There were no significant changes from baseline in EDSS scores during the 12-month period. There were no unexpected safety findings during the extension as compared to the 6 month PL-controlled phase. Adverse events reported most frequently (>15% of patients in at least one group treated with FTY720 for up to 12 months) were nasopharyngitis, influenza and headache.
Conclusion: This 6-month, dose-blinded extension provides further support for the positive results of the 6 month placebo-controlled phase. There was no clear difference in the efficacy of the two doses. FTY720 was well tolerated with no unexpected safety findings.
Study supported by Novartis Pharma AG Basel