[P06.128] Oral Fingolimod (FTY720) Shows Sustained Low Rates of Clinical and MRI Disease Activity in Patients with Relapsing Multiple Sclerosis: Four-Year Results from a Phase II Extension

Xavier Montalban, Barcelona, Spain, Paul O'Connor, Toronto, ON, Canada, Jack Antel, Montreal, QC, Canada, Giancarlo Comi, Milan, Italy, Ernst-Wilhelm Radue, Ana De Vera, Harald Pohlmann, Göril Karlsson, Ludwig Kappos, Basel, Switzerland, FTY720D2201 Study Group

OBJECTIVE: To report the long-term effects on disease activity, safety and tolerability of once-daily oral fingolimod (FTY720) administered for up to 48 months (M). BACKGROUND: Oral fingolimod (1.25 and 5.0 mg), a sphingosine 1-phosphate receptor modulator, reduced the cumulative number of gadolinium (Gd)-enhanced lesions by up to 80% and annualized relapse rate (ARR) by >50% vs placebo (ARR 0.350.36 vs 0.77, respectively) in a 6-month, placebo-controlled study in 281 patients with relapsing multiple sclerosis (MS). Patients who completed this core study could enter an extension study. DESIGN/METHODS: Placebo-treated patients entering the extension were re-randomized to 1.25 or 5.0 mg while the fingolimod groups remained unchanged. From M24, all patients received open-label fingolimod 1.25 mg. RESULTS: 155 of 250 patients (62%) entering the extension completed M48. Fingolimod showed sustained low ARR (M48, 0.21; M36, 0.24; M24, 0.25); 6370% of continuously-treated patients and 51% of patients initially receiving placebo were relapse-free at M48. Inflammatory activity on MRI remained low; 97% of all patients remained free of Gd-enhanced lesions at M48 (vs 89% at M36; 85% at M24) and 83% had no new T2 lesions since M36 (vs 75% for M24M36; 71% for M12M24). In patients treated up to M48, the adverse event (AE) profile remained similar to that reported previously. The most frequently reported AEs were nasopharyngitis (35%), headache (31%), influenza (20%), fatigue (19%), back pain (17%) and elevated alanine aminotransferase levels (15%). No new cases of serious infections, skin malignancy or herpes zoster infections were reported during M36M48, and only 5 patients (2.9%) discontinued due to AEs. CONCLUSIONS/RELEVANCE: Oral fingolimod continued to show sustained low ARR and MRI activity in patients treated up to M48 with no significant change in the safety profile from M36 to M48. The ongoing phase III program will further characterize the safety and efficacy of oral fingolimod in MS. Supported by: Novartis Pharma AG, Basel, Switzerland.
Category - MS and Related Diseases - Clinical Science

Wednesday, April 29, 2009 4:00 PM

Poster Session VI: Multiple Sclerosis: Therapeutics I (4:00 PM-7:00 PM)