THE WOODLANDS, Texas,
Jan. 6, 2011 /PRNewswire/ -- Lexicon
Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company
focused on discovering breakthrough treatments for human disease,
announced data from a recently completed clinical trial and
mechanistic study of a solid oral dose formulation for LX4211, a
dual inhibitor of sodium-glucose co-transporters 1 and 2 (SGLT1 and
SGLT2).
Results from the study demonstrated that administration of a 300
mg solid oral tablet dose of LX4211, administered as two 150 mg
tablets, significantly increased total GLP-1 (p=0.001), active
GLP-1 (p=0.032) and PYY (p=0.004), important mediators of glycemic
and appetite control as well as other metabolic parameters.
Notably, single doses of LX4211 produced rapid and
significant improvement in post-prandial glucose (PPG) and fasting
plasma glucose (FPG), consistent with results seen in the previous
Phase 2 study. Pharmacokinetic and pharmacodynamic data from the
study indicated that the solid oral formulation worked as well as
or better than the liquid formulation on key parameters of hormonal
release, PPG and FPG. Lexicon plans to move the tablet
formulation forward into a Phase 2b study in the second quarter of
2011.
"The significant elevations of GLP-1 levels observed in the
study are particularly important given its established relevance in
the treatment of diabetes," said Brian Zambrowicz, Ph.D., executive
vice president and chief scientific officer. "Newly observed
in this study was the effect of LX4211 on increasing circulating
levels of PYY. We believe the rapid reduction in blood sugar
levels after meals, the increase in GLP-1 and the increase in PYY
are all associated with SGLT1 inhibition by LX4211 in the
gastrointestinal tract."
PYY and GLP-1 are gastrointestinal-derived peptide hormones that
have been associated with producing satiety and reducing food
intake. PYY has been studied as an anti-obesity agent, and
GLP-1 is a mediator of insulin and glucagon secretion. As
nutrients enter the small intestine, PYY and GLP-1 are co-secreted
into the circulation by neuroendocrine cells (L cells) of the
gastrointestinal tract.
"We have established a solid tablet formulation suitable for
further development and will continue to explore LX4211's unique
mechanism of action in the treatment of diabetes and the hormonal
control of metabolism," said Arthur T. Sands, M.D., Ph.D.,
president and chief executive officer. "We believe the results of
this study provide further evidence that dual inhibition of SGLT1
and SGLT2 may provide enhanced glycemic control over SGLT2
inhibition alone, consistent with the remarkable results observed
in our Phase 2a clinical trial of LX4211."
About the Clinical Trial
The clinical trial compared a new solid oral dose formulation of
LX4211 to the liquid dose formulation used in prior clinical trials
of LX4211. The trial employed a randomized, triple-cross over
design during which 12 patients with type 2 diabetes each received
300 mg of LX4211 in different dose forms. Patients were
administered a single dose of two 150 mg tablets, six 50 mg tablets
or a 300 mg liquid dose formulation in varying sequences at 5-day
intervals over a total period of 15 days. Pharmacokinetic and
pharmacodynamic measures were monitored at frequent time points at
baseline and after administration of each of the three dose forms
with baseline measures prior to dosing used as controls.
Additional details regarding the results from this latest
clinical study will be presented on Monday,
January 10, 2011 at the JP Morgan Healthcare Conference.
A live webcast of the presentation will be available through
Lexicon's corporate website at www.lexpharma.com. An archived
version of the presentation will be available for 30 days after the
event.
About LX4211
LX4211 is an orally-delivered small molecule under development
as a potential treatment for diabetes. LX4211 inhibits both
sodium-glucose co-transporter type 1 (SGLT1) and sodium-glucose
co-transporter type 2 (SGLT2). SGLT2 is a transporter
responsible for most of the glucose reabsorption performed by the
kidney. SGLT1 is a transporter responsible for glucose and
galactose absorption in the gastrointestinal tract, and to a lesser
extent than SGLT2, glucose reabsorption in the kidney. For
more information on LX4211 please visit www.lexpharma.com.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering
and developing breakthrough treatments for human disease.
Lexicon currently has four drug candidates in development for
autoimmune disease, carcinoid syndrome, diabetes, and irritable
bowel syndrome, 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 the characterization of the
results observed in the referenced clinical trial and prior
clinical trials of LX4211 as positive or remarkable, the mechanism
of action of LX4211, and the potential therapeutic and
commercial potential of LX4211 generally. 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. Information identifying such important factors is
contained under "Factors Affecting Forward-Looking Statements" and
"Risk Factors" in Lexicon's annual report on Form 10-K for the year
ended December 31, 2009, 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.