Pharmacological effects of CS-0777, a selective sphingosine 1-phosphate receptor-1 modulator: Results from a 12-week, open-label pilot study in multiple sclerosis patients

• Published in: Journal of Neuroimmunology Vol. 246; no. 1-2; pp. 100 - 107
• Main Authors: Moberly, James B., Ford, Daniel M., Zahir, Hamim, Chen, Shuquan, Mochizuki, Takashi, Truitt, Kenneth E., Vollmer, Timothy L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.05.2012; Elsevier BV
• Subjects: Administration, Oral; Allergy and Immunology; Amino Alcohols; Amino Alcohols - adverse effects; Amino Alcohols - pharmacokinetics; Amino Alcohols - pharmacology; Autoimmune disease; Bradycardia; CD4-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8 T cell subsets; Dose-Response Relationship, Immunologic; Down-Regulation; Down-Regulation - drug effects; Down-Regulation - immunology; Fingolimod; Humans; Lymphocyte Subsets; Lymphocyte Subsets - drug effects; Lymphocyte Subsets - immunology; Lymphocyte Subsets - pathology; Lymphopenia; Lymphopenia - immunology; Lymphopenia - metabolism; Lymphopenia - pathology; Lysophospholipids; Lysophospholipids - metabolism; Multiple Sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Neurology; Pilot Projects; Pyrroles; Pyrroles - adverse effects; Pyrroles - pharmacokinetics; Pyrroles - pharmacology; Receptors, Lysosphingolipid; Receptors, Lysosphingolipid - metabolism; S1PR1; Sphingosine; Sphingosine - analogs & derivatives; Sphingosine - metabolism; S1PR1; Autoimmune disease; Bradycardia; Lymphopenia; Fingolimod; CD8 T cell subsets
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2012.03.007

CS-0777 is a selective sphingosine 1-phosphate receptor-1 modulator under investigation for treatment of multiple sclerosis (MS). We conducted an open-label, pilot study in 25 MS patients to assess the safety, pharmacokinetics, pharmacodynamics and exploratory efficacy of oral CS-0777 (0.1, 0.3 and 0.6mg), administered once weekly or every other week for 12weeks. CS-0777 resulted in a pronounced, dose-dependent decrease in lymphocytes and CD4 T cell subsets, which returned to baseline within 4weeks after the last dose. Overall, CS-0777 was safe and well-tolerated. These results require confirmation in a double-blind, placebo-controlled and adequately powered phase 2 study in MS.