Phase 2 Trial of LX4211 Demonstrates Significant and Rapid Improvements in Multiple Parameters in Type 2 Diabetic Patients
- Significant Improvements in Glycemic Control - Significant Reduction in HbA1c within Four Weeks - Favorable Safety, Cardiovascular and Metabolic Profile Observed
THE WOODLANDS, Texas, Jan. 20 /PRNewswire-FirstCall/ -- Lexicon
Pharmaceuticals, Inc. (NASDAQ:LXRX) , a biopharmaceutical company
focused on discovering breakthrough treatments for human disease,
obtained positive results from a recently completed Phase 2 study
of LX4211 in patients with type 2 diabetes mellitus. LX4211 is a
once-per-day, orally-delivered, small molecule drug candidate that
inhibits the sodium-dependent glucose transporter 2 (SGLT2),
lowering the accumulation of glucose in the body and reducing
caloric load. LX4211, dosed as a single agent, provided
improvements in glycemic control, demonstrating statistically
significant benefits in the primary and multiple secondary efficacy
endpoints.
"Results from this important first trial of LX4211 in diabetic
patients exceeded our expectations," said Dr. Philip M. Brown,
senior vice president of clinical development at Lexicon. "Rapid
improvement in multiple parameters of diabetes, meaningful weight
loss, a favorable safety profile and the fact that LX4211-treated
patients exhibited improvements in clinically-important metabolic
and cardiovascular parameters within four weeks on a single agent
is remarkable."
The recently completed study was a four-week, randomized,
double-blind, placebo-controlled study in 36 patients with type 2
diabetes. Patients were randomized to receive either placebo (n=12)
or LX4211, 150 mg (n=12) or 300 mg (n=12), once daily for 28 days.
Patients were sequestered, provided a controlled diet and monitored
closely throughout the study period.
There was a marked decrease in fasting plasma glucose throughout the treatment period in both dose groups, with reductions at week four of 53.4 mg/dl and 65.9 mg/dl in the 150 mg and 300 mg dose groups, respectively, as compared to 15.1 mg/dl for placebo. These decreases in fasting plasma glucose relative to placebo were statistically significant for both LX4211 dose groups (p=0.001 and p<0.001, respectively). Notably, a substantial percentage (42%) of patients in the 300 mg dose group achieved fasting plasma glucose levels of <105 mg>
Importantly, after only four weeks of dosing, average percent
hemoglobin A1c (HbA1c), a measure of blood glucose levels over
time, was significantly reduced by 1.15 in the 150 mg dose group
(p=0.036) and by 1.25 in the 300 mg dose group (p=0.017), as
compared to 0.49 in the placebo group. HbA1c levels were reduced to
less than or equal to 7% for half the patients in both dose groups;
baseline levels were 8.22%, 8.50% and 8.20% for the 150 mg, 300 mg,
and placebo groups, respectively. Patients in both dose groups also
exhibited significantly improved glucose tolerance in response to
oral glucose tolerance testing as compared to patients receiving
placebo (p<0.001 for both dose groups), as measured by area
under the curve (AUC). Consistent with the mechanism of action of
LX4211, there was also a significant, dose-dependent increase in
24-hour urinary glucose excretion throughout the study period
relative to placebo in both dose groups (p<0.001 at all time
points measured).
With respect to broader metabolic and cardiovascular safety
parameters, patients in both dose groups showed weight reduction
accompanied by decreased blood pressure and triglycerides relative
to placebo. LX4211 demonstrated a favorable safety profile in the
study with no dose-limiting toxicities. Adverse events were
generally mild and equally distributed across all groups, including
the placebo group.
"The magnitude and rapid response in glycemic control, combined
with the triglyceride reduction, may distinguish LX4211 from other
agents in this class," said Dr. Brian Zambrowicz, chief scientific
officer of Lexicon. "We now believe that the action of LX4211
cannot be entirely explained by glucose excretion in the urine
alone, but may also relate to secondary events that both further
enhance glycemic control and provide the other metabolic
improvements we have witnessed in this study."
In addition to LX4211, Lexicon has three additional drug
candidates progressing through Phase 2 clinical trials: LX1032, a
peripherally-available serotonin synthesis inhibitor for carcinoid
syndrome; LX2931, an S1P lyase inhibitor for rheumatoid arthritis;
and LX1031, a locally-acting serotonin synthesis inhibitor for
irritable bowel syndrome, which recently completed a Phase 2a
clinical trial with positive results.
"We believe the latest encouraging results with LX4211
demonstrate the potential for a therapeutic benefit for patients
with type 2 diabetes," said Dr. Arthur T. Sands, president and CEO
of Lexicon. "With positive results within the last few months from
Phase 2 clinical trials of two candidates, we are proceeding with
confidence that our drug discovery platform has produced
investigational new drugs with great promise for patients."
For more information about Lexicon's clinical development
programs, please visit www.lexpharma.com.
About the LX4211 Mechanism of Action
LX4211 was developed at Lexicon as a potent inhibitor of the
sodium glucose cotransporter 2 (SGLT2), a transporter responsible
for the majority of glucose reabsorption by the kidneys. Lexicon
found that mouse knockouts engineered to lack the SGLT2 gene are
healthy and require less insulin to manage a glucose challenge.
LX4211 may potentially treat diabetes by improving glycemic control
as well as providing other metabolic benefits.
About Diabetes
Diabetes mellitus is a common metabolic disorder associated with
abnormally high blood sugar levels. Diabetes is classified as
either type 1, which is characterized by severely diminished
insulin production, or type 2, which is characterized by moderately
diminished insulin production in conjunction with insulin
resistance (insensitivity of the tissues of the body to insulin).
Insulin is a hormone that regulates blood glucose levels. Diabetes
can seriously impair overall quality of life and may lead to
multiple complications including heart disease, stroke, and kidney
failure. According to the International Diabetes Federation, more
than 245 million people have diabetes, with type 2 diabetes being
the most prevalent.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering
breakthrough treatments for human disease. Lexicon currently has
five drug candidates in development for autoimmune disease,
carcinoid syndrome, diabetes, glaucoma and irritable bowel
syndrome, all of which were discovered by the company's research
team. The company 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 safety
and efficacy profile of LX4211 observed in the Phase 2 clinical
trial as positive or favorable, the characterization of the results
of the Phase 2 clinical trial of LX4211 as demonstrating the
potential for a therapeutic benefit for patients with type 2
diabetes, 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, 2008, 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.
CONTACT: D. Wade Walke, Ph.D., Director, Corporate
Communications of
Lexicon Pharmaceuticals, Inc., +1-281-863-3046, wwalke@lexpharma.com
Web Site: http://www.lexpharma.com/
Posted: January 2010
