Lexicon Announces Top-Line Phase 2a Data for LX2931 in Patients with Rheumatoid Arthritis

THE WOODLANDS, Texas, Dec. 14, 2010 /PRNewswire-FirstCall/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced top-line results from a recently completed Phase 2a study of LX2931 in patients with rheumatoid arthritis (RA).  LX2931 is an orally-delivered, small molecule drug candidate that inhibits sphingosine-1-phosphate (S1P) lyase, an enzyme important for modulating the immune system by controlling S1P levels in lymphoid tissues. The trial was the first test of this new anti-inflammatory mechanism of action in patients and was designed to obtain safety and tolerability information and signals of efficacy. 

Results from the 12-week, randomized, double-blind, placebo-controlled study in 208 patients with RA demonstrated that all three doses tested, 70 mg, 110 mg, and 150 mg given once per day, were well tolerated over the 12-week treatment period.  Taken together, the data also suggested that patients treated with 150 mg once daily of LX2931 showed an improvement in the primary efficacy endpoint, the percentage of patients achieving an American College of Rheumatology 20 (ACR20) response at week 12 (60% versus 49% for placebo).  Patients treated with 70 mg or 110 mg once daily did not indicate improvement in the ACR20 at week 12 (44% and 41% response rates, respectively) relative to placebo. Adverse events for all three LX2931 dose groups were predominantly mild-to-moderate, with frequencies similar to the placebo group.

"We believe the preliminary signal of efficacy and the favorable safety profile observed in this trial supports further study of additional higher doses of LX2931 as an orally-delivered treatment for rheumatoid arthritis," said Dr. Arthur T. Sands, president and chief executive officer of Lexicon.  "While we were disappointed by the unusually high placebo effect in this trial, we are encouraged by the excellent overall safety profile observed in the first test of this new mechanism of action in patients with RA." 

The company intends to commence discussions with potential pharmaceutical partners to pursue further development of LX2931 in rheumatoid arthritis.

Clinical Trial

The recently completed study was a 12-week, randomized, double-blind, placebo-controlled study in 208 patients on stable dose methotrexate with progressing rheumatoid arthritis. Patients were randomized to receive either placebo (n=49) or LX2931, 70 mg (n=55), 110 mg (n=54), or 150 mg (n=50), once daily for 12 weeks.  In addition to measurements to assess the drug's safety, efficacy endpoints included the primary endpoint, ACR20 at week 12, as well as secondary endpoints of ACR20, ACR50, ACR70 and DAS28 at weeks 4, 8 and 12.  The trial was conducted at sites within the United States and Eastern Europe.

About S1P Lyase and the Role of S1P in Autoimmune Disease

S1P lyase is responsible for the irreversible degradation of S1P, a biologically active lipid that can act as a second messenger in signal transduction pathways important for immune function.  Changes in local S1P concentrations and gradients in immune tissues can modify lymphocyte migration, inflammatory cell response, and affect barrier function of endothelial cells.  Inhibiting S1P lyase results in an increase in S1P levels, primarily in lymphoid tissues.  The physiological outcome of raising S1P levels in the lymphoid system is immune-modulation, which offers new opportunities for treating autoimmune and inflammatory diseases.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease.  Lexicon currently has four drug candidates in mid-stage development for diabetes, irritable bowel syndrome, carcinoid syndrome and rheumatoid arthritis, all of which were discovered by Lexicon's research team.  Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets.  Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs.

In addition to LX2931, Lexicon has three other drug candidates progressing through Phase 2 clinical trials:  LX4211, an orally-delivered, once-daily, dual inhibitor of sodium glucose transporter 1 (SGLT1) and SGLT2 for type 2 diabetes; LX1031, a locally-acting serotonin synthesis inhibitor for irritable bowel syndrome; and LX1032, a peripherally-available serotonin synthesis inhibitor for carcinoid syndrome.  For additional information about Lexicon and its programs, please visit www.lexpharma.com.

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