Date: 2016-09-29
Type of information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
Company: Actelion (Switzerland)
Product: ponesimod and Tecfidera® (dimethyl fumarate)
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 (RMS)
Therapeutic area: Neurodegenerative diseases
Country: USA
Trial
details: POINT (POnesImod aNd Tecfidera) is a prospective, multicenter, randomized, double-blind, parallel group, add-on, placebo-controlled, superiority study with ponesimod in patients with relapsing multiple sclerosis. The study is designed to compare the efficacy, safety, and tolerability of add-on therapy with ponesimod 20 mg vs. placebo in adult patients with active RMS who are treated with dimethyl fumarate (Tecfidera®). Approximately 600 patients receiving dimethyl fumarate twice daily for at least 6 months will be randomized in a 1:1 ratio to ponesimod 20 mg or placebo. Treatment will be given until the last patient enrolled into the study has been treated for 60 weeks, with expected average treatment duration of 2 years, and for a maximum duration of 3 years. Enrollment is expected to start before the end of 2016. The primary objective of the study is to determine whether add-on therapy with ponesimod reduces relapse frequency as compared to placebo in patients with active relapsing multiple sclerosis who are treated with Tecfidera. The primary endpoint is the Annualized Relapse Rate (ARR), which is defined as the number of confirmed relapses per patient and year, from randomization up to the end of the study. Secondary objectives focus on assessing the efficacy, safety and tolerability of add-on therapy with ponesimod versus placebo in patients with relapsing multiple sclerosis who are treated with Tecfidera. Corresponding efficacy and safety endpoints include the time to 12-week CDA (Confirmed Disability Accumulation) and Adverse Events leading to premature discontinuation of treatment. (NCT02907177)
Latest
news: * On September 29, 2016, Actelion announced that it will investigate the use of combination therapy with ponesimod and dimethyl fumarate (Tecfidera®) for patients with relapsing multiple sclerosis (RMS). The POINT study - which will be conducted under a Special Protocol Assessment (SPA) agreement with the FDA - is the first to assess an all-oral treatment paradigm with the objective to better control this progressive, debilitating neurological disorder. Despite recent advances in the treatment of RMS, there remains a considerable medical need for improved long-term disease control without compromising patient safety. While combination therapy is a logical next step, it has likely been limited due to the potential risks associated with the long duration of action of existing products. Ponesimod, with its short half-life and rapid reversibility, could provide physicians with greater flexibility and control of patient treatment. Actelion has generated encouraging preclinical data that suggests the combination of ponesimod and dimethyl fumarate can be beneficial while not compromising safety. Actelion initiated the Phase III program in RMS in April 2015 with Optimum, a superiority study to compare the efficacy and safety of ponesimod to that of teriflunomide (Aubagio®). Enrollment for this study is expected to be completed around the end of 2016.
