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LX2931 |
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Indications Rheumatoid arthritis and other autoimmune diseases Stage of Development Phase 2  Clinical Trial Enrollment For enrollment information for the Phase 2 clinical trial, please visit http://www.clinicaltrials.gov/ and reference LX2931 or click here. Clinical Status Lexicon initiated a Phase 2 study with LX2931 in patients with rheumatoid arthritis in August 2009. The clinical trial is planned as a 12 week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX2931 and its effects on symptoms associated with rheumatoid arthritis. Previously, Lexicon successfully completed Phase 1 clinical trials of LX2931. Initial results in healthy volunteers demonstrated a potent, dose-dependent reduction in circulating lymphocytes, suggesting that the target of LX2931 may represent a new mechanism for regulating the immune response. For additional information about the results of this study, please view our video presentation  . Lexicon also completed a drug-drug interaction study of LX2931 in patients with rheumatoid arthritis in March 2009. Top-line results from the trial indicated that LX2931 was well tolerated in combination with methotrexate, and no clinically significant drug-drug interactions were observed. Methotrexate is the current standard of care for patients with rheumatoid arthritis. Overview LX2931 is an orally-delivered small molecule under development for the potential treatment of autoimmune diseases such as rheumatoid arthritis. Inappropriate inflammatory cell response is associated with autoimmune diseases, a spectrum of disorders in which the immune system malfunctions and causes the body to attack its own organs, tissues, and cells. LX2931 is intended to regulate the activity of inflammatory cells, including lymphocytes, in the body during an autoimmune response.
Key Target The target for LX2931 is sphingosine-1-phosphate lyase (S1P lyase), an enzyme in the sphingosine-1-phosphate (S1P) pathway associated with the body's inflammatory response. From research conducted in the Genome5000TM program, Lexicon scientists discovered that mice lacking this enzyme have increased retention of immune cells in the thymus and spleen with a corresponding reduction in the deployment of T-cells and B-cells into the circulating blood, resulting in a reduced immune response.
Preclinical Data
T. Oravecz, K. Frazier, M. Donoviel, J. T. Bagdanoff, B. Brooks, D. Augeri and P. Brown (2009) Sphingosine 1-Phosphate Lyase is a Potential Therapeutic Target for Autoimmune Disease. 2009 FASEB: Lysophospholipid Mediators in Heath and Disease. R. Fleischmann, K. Frazier, J. Freiman, B. Brooks, M. S. Donoviel, T. Oravecz, D. Augeri, W. Heydorn, M. Kelly and P. Brown (2009). Co-Administration of the Oral S1P-Lyase Inhibitor LX2931 (LX3305) with Methotrexate was Well Tolerated Over 14 Days in Patients with Stable Rheumatoid Arthritis. 2009 American College of Rheumatology Meeting. Frazier K, Brooks B, Freiman J, Oravecz T, Augeri D, and Brown P (2009). LX2931: Potential Small Molecule Treatment for Rheumatoid Arthritis (RA) and Other Inflammatory Disorders. 2009 Annual Meeting of the European League Against Rheumatism (EULAR). Poster P. Brown, K. Frazier, D. Augeri, D. W. Walke, C. Pappas, B. Brooks, M. Donoviel and T. Oravecz (2008) LX2931: A Potential Small Molecule Treatment for Autoimmune Disorders. ACR/ARHP Annual Scientific Meeting Brown P, Frazier K, Augeri, D, Walke DW, Pappas C, Brooks B, Donoviel, M, and Oravecz T (2008). LX2931: A Potential Small Molecule Treatment for Autoimmune Disorders. 2008 Annual Meeting of the American College of Rheumatology. Poster T. Oravecz, M.S. Donoviel, S.J. Anderson, K.Carson, W. Sun, J. Swaffield, Q. Liu, S.D. Kimball, J.R. Piggott, A.J. Main, B.P. Zambrowicz, A.T. Sands, C.A. Turner, D.J. Augeri (2007). Genetic and Chemical Inhibition of Sphingosine-1-Phosphate Lyasae Results in Peripheral Lymphopenia and Alleviates Disease Development in Animal Models of Inflammation and Autoimmunity. |
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