THE WOODLANDS, Texas,
Sept. 9, 2016 /PRNewswire/
-- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced
today that the pivotal inTandem1 Phase 3 clinical trial of
sotagliflozin met its primary endpoint, showing a statistically
significant reduction in A1C at 24 weeks in patients with type 1
diabetes on a background of optimized insulin.
Top-line results from the Phase 3 study showed that patients
treated with sotagliflozin had a mean A1C reduction from baseline
of 0.43% on 200mg once daily sotagliflozin dose (p<0.001) and a
reduction of 0.49% on 400mg once daily sotagliflozin dose
(p<0.001) as compared to a reduction of 0.08% on placebo after
24 weeks of treatment, meeting the study's primary endpoint.
This statistically significant and clinically meaningful
improvement in A1C for both doses of sotagliflozin was achieved
without an increase in severe hypoglycemia, one of the most
prevalent serious health challenges in type 1 diabetes, which was
seen less frequently in both treatment arms than placebo.
"We are extremely pleased with these top-line results and the
potential long-term benefits that sotagliflozin may bring to people
with type 1 diabetes," said Lexicon President and Chief Executive
Officer Lonnel Coats. "We
believe these results provide evidence that sotagliflozin, with its
novel dual inhibition of both SGLT-1 and SGLT-2, is particularly
well suited to help these individuals achieve better A1C levels
without increasing and possibly reducing the risk of severe
hypoglycemia."
"Our companies are working together to develop this compound for
the treatment of type 1 and type 2 diabetes," said Jorge Insuasty, Senior Vice President, Head of
Global Development, Sanofi. "These top-line results highlight
potential benefits of sotagliflozin when treating adults with type
1 diabetes. We congratulate our partners on this positive
outcome and look forward to further exploring this compound for the
treatment of adults with type 2 diabetes when Sanofi begins the
Phase 3 program later this year."
"The inTandem1 study is part of the largest Phase 3 program for
an oral anti-diabetic agent in type 1 diabetes to date," said
Anne Peters, M.D., Professor of
Medicine at the Keck School of Medicine of USC, Director of the USC Clinical Diabetes Programs and Chairman of the
Sotagliflozin Type 1 Diabetes Steering Committee.
"Sotagliflozin demonstrated compelling, significant and clinically
meaningful A1C reduction with no increase in severe hypoglycemia
and a slight risk of DKA. If approved, sotagliflozin could
represent a significant addition to the current standard of care
and potentially allow patients with type 1 diabetes to better
manage their diabetes while on insulin."
About inTandem1
The double-blind, placebo controlled, Phase 3 study known as
inTandem1 enrolled 793 patients in the
United States and Canada
with type 1 diabetes on insulin pump or multiple daily injection
therapy who had an A1C level entering the study between 7.0% and
11.0%, which corresponds to an estimated average blood sugar of 154
mg/dl to 269 mg/dl (8.6 mmol/l to 15.0 mmol/l). The three-arm
study evaluated two doses of sotagliflozin, 200mg and 400mg, each
taken once daily before the first meal of the day, against placebo.
Prior to randomization, insulin was optimized for all
patients over a six-week period, with the objective of improving
glycemic control using insulin alone. After completion of
this optimization period, patients were maintained on optimized
insulin and randomized to one of two doses of sotagliflozin or
placebo, and their baseline, post-optimization A1C was measured.
The mean baseline A1C level at the time of randomization
after the six-week optimization period was 7.6% for all three dose
arms.
The primary endpoint of the study was change in A1C from
baseline after a 24-week period of treatment. The trial has a
double-blind long term extension of 28-weeks, with a total
treatment duration of 52-weeks. There were 268 patients in the
placebo arm, 263 patients in the 200mg dose arm and 262 patients in
the 400mg dose arm. The overall mean placebo adjusted A1C
reduction was 0.35% in the 200mg dose arm (p<0.001) and 0.41% in
the 400mg dose arm (p<0.001).
Sotagliflozin was generally well tolerated. Across all
three dose arms (placebo, 200mg, 400mg), the incidence of
treatment-emergent adverse events (AEs) were 67.5%, 67.3% and
71.0%, respectively; the incidence of serious AEs (SAEs) were 3.4%,
3.8% and 6.9%, respectively; and discontinuation due to AEs were
1.5%, 1.1% and 3.8%, respectively. There were no reported
deaths in the study.
Two primary safety concerns for patients with type 1 diabetes
are severe hypoglycemia and diabetic ketoacidosis (DKA). The
number of patients with severe hypoglycemic events during the
24-week treatment period was 18 (6.7%), 11 (4.2%), and 12 (4.6%) in
the placebo, 200mg and 400mg dose arms, respectively. The
number of patients with DKA events during the 24-week treatment
period was 0 (0.0%), 3 (1.1%), and 8 (3.1%) in the placebo, 200mg
and 400mg dose arms, respectively.
Lexicon is conducting another similar pivotal Phase 3 clinical
trial predominantly in Europe
(inTandem2), which is expected to report top-line results by the
end of the year. The third type 1 diabetes Phase 3 clinical
trial, inTandem3, is underway globally and is studying
approximately 1,400 patients treated with sotagliflozin 400mg once
daily or placebo on a background of any insulin therapy, but
without insulin optimization prior to randomization. Sanofi is
expected to commence Phase 3 clinical trials for sotagliflozin in
patients with type 2 diabetes by the end of the year.
About Sotagliflozin
Discovered using Lexicon's unique approach to gene science,
sotagliflozin is a first-in-class, oral dual inhibitor of two
proteins responsible for glucose regulation known as sodium-glucose
co-transporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is
responsible for glucose absorption in the gastrointestinal tract,
and SGLT2 is responsible for glucose reabsorption by the kidney.
Sotagliflozin has been shown in a Phase 2 study to improve glycemic
control in people with type 1 diabetes while reducing their need
for mealtime insulin.
Lexicon entered into a collaboration and license agreement with
Sanofi in November 2015 under which
Lexicon granted Sanofi an exclusive, worldwide, royalty-bearing
right and license to develop, manufacture and commercialize
sotagliflozin. Lexicon is responsible for all clinical
development activities relating to type 1 diabetes and retains an
exclusive option to co-promote and have a significant role, in
collaboration with Sanofi, in the commercialization of
sotagliflozin for the treatment of type 1 diabetes in the United
States. Sanofi is responsible for all clinical development
and commercialization of sotagliflozin for the treatment of type 2
diabetes worldwide and is solely responsible for the
commercialization of sotagliflozin for the treatment of type 1
diabetes outside the United
States.
Lexicon Conference Call
Lexicon management will hold a conference call and webcast to
discuss the inTandem1 Phase 3 top-line results at 8:00 a.m. Eastern Time on September 9, 2016. The dial-in number for
the conference call is 888-645-5785 (within the US/Canada) or 970-300-1531 (international).
The conference ID for all callers is 79513441. Investors can
access a live webcast of the call at www.lexpharma.com. An
archived version of the webcast will be available on the website
through October 9, 2016.
About Lexicon
Lexicon is a fully integrated biopharmaceutical company that is
applying a unique approach to gene science based on Nobel
Prize-winning technology to discover and develop precise medicines
for patients with serious, chronic conditions. Through its
Genome5000™ program, Lexicon scientists have studied the role and
function of nearly 5,000 genes over the last 20 years and have
identified more than 100 protein targets with significant
therapeutic potential in a range of diseases. Through the precise
targeting of these proteins, Lexicon is pioneering the discovery
and development of innovative medicines to safely and effectively
treat disease. Lexicon has a pipeline of promising drug candidates
in clinical and pre-clinical development in oncology, diabetes and
metabolism. For additional information please visit
www.lexpharma.com.
Safe Harbor Statement
This press release contains "forward-looking statements,"
including statements relating to Lexicon's and its licensees'
clinical development of and regulatory filings for sotagliflozin
(LX4211) and the results and projected timing of clinical trials
and the potential therapeutic and commercial potential of
sotagliflozin. In addition, 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 the risk that clinical studies of
sotagliflozin may be halted, delayed or otherwise not demonstrate
safety or efficacy, the risk that the FDA and other regulatory
authorities may not grant regulatory approval of sotagliflozin in
accordance with Lexicon's currently anticipated timelines or at
all, and the risk that such regulatory approvals, if granted, may
have significant limitations on the approved use of sotagliflozin.
As a result, sotagliflozin may never be successfully
commercialized. Other risks include Lexicon's ability to meet its
capital requirements, successfully conduct preclinical and clinical
development and obtain necessary regulatory approvals of its other
potential drug candidates, 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. Any of these risks,
uncertainties and other factors 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 "Risk Factors" in
Lexicon's annual report on Form 10-K for the year ended
December 31, 2015, 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.
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SOURCE Lexicon Pharmaceuticals, Inc.