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From St. Michael's Hospital (P.O.), Toronto, ON, Canada; Ospedale San Raffaele (G.C.), Milan, Italy; University Hospital Edif. EUI (X.M.), Barcelona, Spain; Montreal Neurological Institute (J.A.), Montreal, QC, Canada; MS MRI Evaluation Centre (E.W.R.) and Neurology and Department of Biomedicine (L.K.), University Hospital, Basel; and Novartis Pharma AG (A.d.V., H.P.), Basel, Switzerland.
Address correspondence and reprint requests to Dr. Paul O'Connor, St. Michael's Hospital, Toronto, ON, Canada oconnorp{at}smh.toronto.on.ca
Objective: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS).
Methods: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits.
Results: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd+) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd+ lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study.
Conclusions: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity.
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; ARR = annualized relapse rate; BP = blood pressure; DLCO = carbon monoxide diffusion capacity; EDSS = Expanded Disability Status Scale; FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; Gd+= adolinium-enhanced; MoA = mechanism of action; MS = multiple sclerosis; MSFC = Multiple Sclerosis Functional Composite; SAE = serious adverse event; ULN = upper limit of normal.
Supplemental data at www.neurology.org
*Members of the FTY720 D2201 Study Group are listed in the appendix.
Supported by Novartis Pharma AG, Basel, Switzerland.
Disclosure: Author disclosures are provided at the end of the article.
Received April 1, 2008. Accepted in final form September 24, 2008.
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