Lexicon announces mid-stage trials for three drugs

BANGALORE, India Lexicon Pharmaceuticals noted in a statement released earlier this week that it has three products in mid-stage studies targeting rheumatoid arthritis, carcinoid syndrome and irritable bowel syndrome, data from all of which are expected by the end of 2009 or early 2010.

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.  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.

With regard to carcinoid syndrome, a group of symptoms associated with carcinoid tumors — tumors of the small intestine, colon, appendix and bronchial tubes in the lungs, Lexicon initiated a Phase 2 study of LX1032in patients July.  The clinical trial was planned as a four-week, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and effects of on symptoms associated with carcinoid syndrome.

LX1032 acts by inhibiting the enzyme tryptophan hydroxylase, the rate-limiting enzyme involved in serotonin biosynthesis and present in metastatic carcinoid tumor cells.  From research conducted in the Genome5000 program, Lexicon scientists found that mice lacking the non-neuronal form of the TPH enzyme have virtually no peripheral serotonin, but do maintain normal levels of brain serotonin.

Also in development, LX1031 for treatment of irritable bowel syndrome also works by inhibiting the enzyme tryptophan hydroxylase. Enrollment in the Phase 2 clinical trial completed in August 2009, four months ahead of schedule.  In all trials completed to date, all dose levels and dosing regimes were well tolerated with infrequent adverse events observed.

LX1031 is an orally-delivered small molecule designed to regulate gastrointestinal function by reducing the amount of serotonin available for receptor activation in the GI tract without affecting serotonin levels in the brain. Serotonin is a key regulator of GI function, and is associated with the most common symptoms of IBS:  problems with bowel motility and GI discomfort.

Unlike LX1031, LX1032 was specifically designed to be better absorbed into the blood stream and, therefore, capable of reducing serotonin production both inside and outside the GI tract without affecting brain serotonin levels.