LX4211 for Diabetes Shown to Reduce Fasting and Post-Prandial Blood Sugar in Healthy Subjects

THE WOODLANDS, Texas, Sept. 13, 2011 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, reported positive data from a recently completed clinical trial and mechanistic study of LX4211, a dual inhibitor of the sodium glucose transporters 1 and 2 (SGLT1 and SGLT2).  The favorable safety profile and effects on multiple parameters of glycemic control and cardiovascular health in healthy normal subjects support the broad potential of LX4211 in the treatment of diabetes and associated metabolic conditions.

"Newly observed in this study were the effects of LX4211, in healthy volunteers, of decreasing postprandial glucose levels without hypoglycemia and substantially reducing triglycerides," said Brian Zambrowicz, Ph.D., executive vice president and chief scientific officer.  "Notably, the magnitudes of the reductions in triglycerides were similar to current standard of care prescription and clinical-stage medicines. By contrast, reported results of SGLT2-selective compounds have demonstrated minimal or no reductions in postprandial glucose in healthy subjects and minimal or no triglyceride decreases in either healthy normal volunteers or patients with type 2 diabetes."

Results from the study demonstrated that the 400 mg solid oral dose of LX4211 compared to placebo significantly reduced mean changes from baseline in fasting plasma glucose (p=0.005) and post-prandial glucose levels (p<0.001) in parallel with meaningful mean increases from baseline in total and active GLP-1 (p=0.055 and p=0.003, respectively) as well as PYY (p<0.001).  GLP-1 is associated with improved glucose control and decreased food intake through reduction of appetite.  PYY is a gastrointestinal-derived peptide hormone that has also been associated with reducing food intake and has been studied as an anti-obesity agent. These two gastrointestinal peptides (GLP-1 and PYY) are secreted into circulation by neuroendocrine cells (L cells) as part of a natural homeostatic mechanism that senses nutrient transit through the gastrointestinal tract. Such nutrient sensing and related mechanisms are thought to be enhanced as a result of certain types of bariatric surgery for weight loss and control of diabetes.

LX4211 treatment also produced a 50.2 mg/dL adjusted mean decrease from baseline in triglycerides, consistent with the triglyceride reduction observed in the Phase 2a study in type 2 diabetics.  In addition, LX4211, compared to placebo, produced a significant adjusted mean decrease in serum uric acid (1.52 mg/dL from baseline to last study visit, p=0.005). Serum uric acid is an emerging marker for cardiovascular risk and renal disease.  These data, together with a trend of improved blood pressure observed in the Phase 2a study, demonstrate that LX4211 has effects on multiple cardiovascular and metabolic risk factors.  Also of importance in this study was the safety of LX4211, which showed no hypoglycemia and no abdominal pain or diarrhea, consistent with the favorable safety profile associated with dual inhibition of SGLT1 and SGLT2 by LX4211 in previous clinical trials. Enrollment in Lexicon's ongoing Phase 2b study of LX4211 in patients with type 2 diabetes is on schedule, with results anticipated in the first half of 2012.

"We have now observed results from several clinical studies of LX4211 which consistently support the concept of dual SGLT1/SGLT2 inhibition for the treatment of diabetes and indicate a long-term opportunity in diabetes prevention," said Pablo Lapuerta, M.D., senior vice president of clinical development and chief medical officer. "The favorable metabolic effects in healthy subjects, together with the safety profile observed to date, suggest that LX4211 could be considered earlier in the diabetes treatment paradigm, perhaps including the potential treatment of pre-diabetes in patients with impaired glucose tolerance or impaired fasting glucose (IGT/IFG)."

About the Clinical Trial

The clinical trial was designed to assess the effect of different LX4211 dose schedules relative to meal time  in healthy subjects when taken as a single daily dose (400 mg) or a split dose (200 mg twice daily).  Subjects were randomized to LX4211 in an ordered sequence to assess the pharmacodynamic effects of different dosing times, ranging from 1 hour prior to meals to immediately prior to meals.  Pharmacodynamic effects, include urinary glucose excretion, fasting plasma glucose, insulin, PYY and GLP-1 (total and active) were assessed at multiple time points during the 12-day dosing period.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease.  Lexicon currently has four drug programs 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.  For additional information about Lexicon and its programs, please visit www.lexpharma.com.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX4211, including characterizations of the results of and projected timing of clinical trials, and the potential therapeutic and commercial potential, of LX4211. This press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information.  All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon's ability to successfully conduct clinical development of LX4211 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements.  Unless specifically indicated otherwise, results reported as trends were not statistically significant. Information identifying such important factors is contained under "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2010, as filed with the Securities and Exchange Commission.  Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE Lexicon Pharmaceuticals, Inc.