THE WOODLANDS, Texas,
Dec. 5, 2016 /PRNewswire/
-- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced
top-line results today from a Phase 2 clinical study of
sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, conducted by
Lexicon in collaboration with JDRF, the leading global organization
funding type 1 diabetes research.
The purpose of this Phase 2 clinical trial, which randomized a
total of 87 patients, was to assess the effects of a once-daily 400
mg dose of sotagliflozin compared to a placebo control in
insulin-treated young adults with type 1 diabetes, aged 18-30
years, and particularly high baseline A1C levels of greater than or
equal to 9.0%, representative of an at-risk population in which
glycemic control and adherence to therapy are substantial
challenges. The study promoted adherence and encouraged
insulin adjustment as needed to achieve glucose control
targets.
Patients treated with sotagliflozin as an adjunct to insulin had
a mean reduction from baseline in A1C of 1.33% after 12 weeks of
treatment. The results for the A1C primary endpoint
numerically favored sotagliflozin, with a placebo-adjusted
reduction of 0.35%, but did not reach statistical significance.
A pre-planned subgroup analysis in patients with A1C at
baseline of less than or equal to 10.0% showed a
statistically-significant reduction in this same A1C primary
endpoint, with sotagliflozin-treated patients achieving a mean
reduction from baseline in A1C of 1.43% and a placebo-adjusted
reduction of 0.75% (p=0.006). In secondary measures:
- Patients treated with sotagliflozin achieved an increase of
approximately one-third in the mean proportion of time spent in the
target range of 70-180 mg/dL (from 33.1% at baseline to 43.6% at
week 12) as measured by continuous glucose monitoring (CGM), as
compared to a slight reduction in time in the target range (from
33.5% at baseline to 32.9% at week 12) for patients treated with
placebo.
- Patients treated with sotagliflozin achieved a mean
placebo-adjusted reduction from baseline to week 12 of 56.6 mg/dL
in two-hour post-prandial glucose (PPG) following a standardized
mixed meal.
- Patients treated with sotagliflozin achieved a mean reduction
of 0.62 kg in body weight from baseline to week 12, as compared to
an increase of 1.75 kg in body weight for patients treated with
placebo.
Sotagliflozin was well tolerated in the study, with a smaller
proportion of patients on sotagliflozin experiencing
treatment-emergent adverse events (AEs) (58.1% on sotagliflozin vs.
61.9% on placebo) and serious AEs (SAEs) (4.7% on sotagliflozin vs.
7.1% on placebo). There were no discontinuations from study
drug due to AEs on sotagliflozin vs. two patients on placebo.
One patient in the sotagliflozin treated arm and two patients in
the placebo arm experienced a severe hypoglycemia event during the
12-week treatment period. No patients treated with
sotagliflozin experienced a diabetic ketoacidosis (DKA) event,
whereas one placebo-treated patient experienced a DKA event during
the 12-week treatment period and two additional patients
experienced a DKA event during the pre-randomization, placebo
run-in period of the study. There were no deaths in the
study.
"Sotagliflozin demonstrated favorable safety in this study in an
at-risk population and continues to show evidence of improvements
in the quality of glucose control consistent with its mechanism of
action," said Pablo Lapuerta, M.D.,
Lexicon's executive vice president and chief medical officer.
"Reductions in post-prandial glucose were consistent with SGLT1
inhibition in the gastrointestinal tract. Better control of
post-prandial glucose will allow patients with type 1 diabetes to
spend more time with glucose in a better range, with low rates of
severe hypoglycemia."
"We applaud the efforts of Lexicon in prioritizing the
development of novel therapies for the multitudes affected by type
1 diabetes. Individuals with type 1 diabetes continue to
experience challenges of disease burden and high levels of A1C, and
we expect at least a subset of those to benefit from novel, add-on
therapies to elicit additional glycemic and metabolic benefits,"
said Sanjoy Dutta, Ph.D., associate
vice president, Translational Development and International
Partnerships at JDRF. "We are looking forward to seeing new
options for individuals with type 1 diabetes, and we truly value
our partnership with Lexicon as we drive our vision of a world
without type 1 diabetes."
About the JDRF Phase 2 Clinical Trial
The double-blind, placebo controlled, Phase 2 study randomized
87 patients, aged 18 to 30, in the United
States with type 1 diabetes on insulin pump or multiple
daily injection therapy who had an A1C level entering the study
greater than or equal to 9.0%. The study evaluated a
once-daily 400 mg dose of sotagliflozin, before the first meal of
the day, against placebo. Prior to randomization, there was a
two-week run-in period in which patients received placebo in
addition to insulin. After completion of the run-in period,
patients were randomized to either sotagliflozin or placebo.
The mean A1C level at baseline, after the two-week run-in
period, was 9.9% in the sotagliflozin-treated arm and 9.7% in the
placebo arm. Following randomization, adjustments in insulin
doses were made when needed in the medical judgment of the
investigator. During the 12-week treatment period, total
insulin use increased in the placebo arm and decreased in the
sotagliflozin arm; basal insulin use increased in both the placebo
and sotagliflozin arms, with a greater increase in the placebo arm;
and bolus insulin use decreased in both the placebo and
sotagliflozin arms, with a greater decrease in the sotagliflozin
arm.
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.
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 announced positive top-line results of its first pivotal
Phase 3 clinical trial of sotagliflozin in patients with type 1
diabetes, on a background of optimized insulin (inTandem1), in
September 2016. Lexicon is conducting a second pivotal Phase
3 clinical trial (inTandem2) from which top-line results are
expected later this month. A third type 1 diabetes Phase 3
clinical trial, inTandem3, is underway globally and is studying
approximately 1,400 patients treated with sotagliflozin 400 mg 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 this year.
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.
About JDRF
JDRF is the leading global organization funding type 1 diabetes
(T1D) research. JDRF's mission is to accelerate life-changing
breakthroughs to cure, prevent and treat T1D and its complications.
To accomplish this, JDRF has invested nearly $2 billion in research funding since its
inception. JDRF is an organization built on a grassroots model of
people connecting in their local communities, collaborating
regionally for efficiency and broader fundraising impact, and
uniting on a national stage to pool resources, passion, and energy.
JDRF collaborates with academic institutions, policymakers, and
corporate and industry partners to develop and deliver a pipeline
of innovative therapies to people living with T1D. JDRF's staff and
volunteers throughout the United
States and its six international affiliates are dedicated to
advocacy, community engagement and its vision of a world without
T1D. For more information, please visit jdrf.org or follow us
on Twitter: @JDRF.
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.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/lexicon-reports-top-line-results-from-phase-2-clinical-trial-conducted-in-collaboration-with-jdrf-300373061.html
SOURCE Lexicon Pharmaceuticals, Inc.