Date: 2015-04-16
Type of information: Initiation of patient enrollment
phase: 3
Announcement: initiation of patient enrollment
Company: Actelion (Switzerland)
Product: ponesimod
Action
mechanism: immunomodulator/ S1P1 immunomodulator. Sphingosine-1-phosphate (S1P) is a sphingolipid released by erythrocytes, platelets, mast cells and other cell types. It is currently established that S1P stimulates at least five different cell surface resident G-protein coupled receptors (GPCRs) - S1P1,2,3,4, and 5. Activation of these GPCRs mediates a complex variety of biological responses such as lymphocyte migration, endothelial cell proliferation, blood vessel constriction and heart rate modulation. Ponesimod is an orally active, selective S1P1 immunomodulator. It prevents lymphocytes from leaving lymph nodes, thereby reducing circulating blood lymphocyte counts and preventing infiltration of lymphocytes into target tissues. The lymphocyte count reduction is rapid, dose-responsive, is sustained with continued dosing and quickly reversed upon discontinuation. Ponesimod does not cause lymphotoxicity: it does not destroy lymphocytes or interfere with their cellular function. Other blood cells e.g. cells of the innate immune system are unaffected and remain available to fight off infection. Ponesimod is therefore considered a promising new oral agent for the treatment of a variety of autoimmune disorders.
Disease: relapsing multiple sclerosis
Therapeutic area: Neurodegenerative diseases
Country: Argentina, Belarus, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Czech Republic, Finland, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Sweden, Turkey, Ukraine, UK, USA
Trial
details: OPTIMUM, is a multicenter, randomized, double-blind, parallel-group, active-controlled superiority study to compare the efficacy and safety of ponesimod to teriflunomide in subjects with relapsing multiple sclerosis. The study aims to determine whether ponesimod is more efficacious than teriflunomide in reducing relapses. The study is expected to enroll approximately 1'100 subjects, randomized in 2 groups in a 1:1 ratio to receive ponesimod 20 mg/day or teriflunomide 14 mg/day, and is expected to last a little over 3 years. (NCT02425644)
Latest
news: * On April 16, 2015, Actelion announced that it is accelerating its clinical development efforts in the field of immunological disorders, following a broad scientific, medical and commercial evaluation of a series of its selective S1P1 receptor modulators, discovered in-house. Actelion has initiated Phase III development with ponesimod, its lead compound, in patients suffering from relapsing multiple sclerosis, with patient enrollment expected imminently. OPTIMUM, is a multicenter, randomized, double-blind, parallel-group, active-controlled superiority study to compare the efficacy and safety of ponesimod to teriflunomide in subjects with relapsing multiple sclerosis. The study aims to determine whether ponesimod is more efficacious than teriflunomide in reducing relapses. The study is expected to enroll approximately 1'100 subjects, randomized in 2 groups in a 1:1 ratio to receive ponesimod 20 mg/day or teriflunomide 14 mg/day, and is expected to last a little over 3 years. An additional study to further characterize the utility and differentiation of ponesimod in multiple sclerosis is being discussed with Health Authorities. The decision to move into Phase III development was based on the Phase IIb dose-finding study with ponesimod in patients with relapsing-remitting multiple sclerosis. A total of 464 patients were randomized into this study and the efficacy, safety and tolerability of three ponesimod doses (10, 20 and 40 mg/day) versus placebo, administered once daily for 24 weeks, was evaluated. The primary endpoint of this study was defined as the cumulative number of new gadolinium-enhancing lesions on T1-weighted magnetic resonance imaging (MRI) scans at weeks 12, 16, 20 and 24 after study drug initiation. A key secondary endpoint of this study was the annualized relapse rate over 24 weeks of treatment. The results of this study were published during 2014 in the Journal of Neurology, Neurosurgery and Psychiatry. Patients who completed 24 weeks of treatment were offered the opportunity to enter into an extension study. This ongoing trial is investigating the long-term safety, tolerability, and efficacy of 10 and 20 mg/day of ponesimod in patients with relapsing-remitting multiple sclerosis, in a double-blind fashion. The study continues to provide extensive safety and efficacy information for ponesimod in this indication, with some patients treated for more than 5 years.
