THE WOODLANDS, Texas,
Oct. 25, 2016 /PRNewswire/ -- Lexicon
Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today that the Phase
2 dose-ranging, inTandem4 clinical trial of dual SGLT1 and SGLT2
inhibitor sotagliflozin met its primary endpoint, showing a
statistically significant reduction in A1C at 12 weeks in patients
with type 1 diabetes.
"The inTandem4 Phase 2 dose-ranging study represents the first
of three clinical trials of sotagliflozin that we expect to read
out in this quarter, including the top-line results from our second
pivotal Phase 3 clinical trial," said Pablo
Lapuerta, M.D., Lexicon's executive vice president and chief
medical officer. "We continue to be very encouraged about the
potential benefits that sotagliflozin may bring to people with type
1 diabetes, especially given that we saw significant glycemic
control benefits coupled with favorable results on important safety
parameters in this trial. In addition, this study provided
the first demonstration in the setting of type 1 diabetes of some
of the important characteristics of sotagliflozin's differentiated
dual SGLT1 and SGLT2 mechanism of action."
The purposes of the Phase 2 inTandem4 study were to confirm the
appropriateness of the doses selected for Lexicon's ongoing Phase 3
program in type 1 diabetes and to evaluate secondary endpoints
relating to sotagliflozin's dual mechanism of action involving
inhibition of SGLT1 in the gastrointestinal (GI) tract and SGLT2 in
the kidney. Both Phase 3 doses of sotagliflozin, 200 mg and
400 mg once-daily, demonstrated statistically significant
(p<0.001 and p=0.006, respectively) and clinically meaningful
reductions in A1C relative to placebo. Patients treated with
sotagliflozin had mean A1C reductions from baseline of 0.60%,
0.84%, and 0.73% on the 75 mg, 200 mg and 400 mg doses,
respectively, after 12 weeks of treatment, as compared to a
reduction of 0.35% on placebo. In addition, sotagliflozin
demonstrated results on several measures consistent with its dual
mechanism of action:
- Post-Prandial Glucose. Consistent with the expected
effects of inhibiting SGLT1 in the GI tract, patients treated with
sotagliflozin achieved dose-related reductions in post-prandial
glucose (PPG) following a standardized meal. Patients treated with
sotagliflozin had mean two-hour PPG reductions from baseline to
week 12 of the study of 20.51 mg/dL, 27.60 mg/dL and 49.67 mg/dL on
the 75 mg, 200 mg and 400 mg doses, respectively, as compared to a
reduction of 0.21 mg/dL on placebo.
- Urinary Glucose Excretion. Consistent with the expected
effects of inhibiting SGLT2 in the kidney moderated by the impact
of GI tract inhibition of SGLT1 on post-prandial blood glucose
levels, sotagliflozin produced relatively modest, dose-dependent
24-hour urinary glucose excretion (UGE). Patients treated with
sotagliflozin had mean 24-hour UGE increases from baseline to week
12 of the study of 42.02 g, 57.99 g and 70.71 g on the 75 mg, 200
mg and 400 mg doses, respectively, as compared to an increase of
0.26 mg on placebo.
- Body Weight. Mean baseline body weight for patients at
the time of randomization ranged from 79.97 kg to 91.92 kg across
the four arms of the study. Patients treated with sotagliflozin
achieved dose dependent reductions in body weight after 12 weeks of
treatment, while patients on placebo gained weight. Patients in the
75 mg, 200 mg and 400 mg dose arms achieved mean weight loss of
0.16 kg, 1.24 kg and 1.48 kg, respectively, as compared to a mean
gain of 1.13 kg for patients in the placebo arm.
- Blood Pressure. Overall, patients treated with
sotagliflozin achieved dose-dependent reductions from baseline to
week 12 in systolic blood pressure ranging from 1.5 mmHg for the 75
mg dose to 4.4 mmHg in the 400 mg dose. Notably, in the subset of
patients with hypertension at baseline (baseline systolic blood
pressure equal to or greater than 130 mmHg), patients in the 400 mg
dose arm experienced a placebo-adjusted reduction of 14.3 mmHg in
systolic blood pressure. This result was consistent with results
seen in a post-hoc analysis of data from Lexicon's Phase 2b study
of sotagliflozin in type 2 diabetes, and supports further
exploration of the potential effects on blood pressure of
inhibition of SGLT1 in the GI tract.
Sotagliflozin was generally well tolerated in the study.
Across all four dose arms (placebo, 75 mg, 200 mg, 400 mg), the
proportions of patients with treatment-emergent adverse events
(AEs) during the 12-week treatment period were 50.0%, 48.6%, 28.6%
and 34.3%, respectively; the incidence of serious AEs (SAEs) were
2.8%, 2.9%, 2.9% and 2.9%, respectively; and discontinuation due to
AEs were 2.8%, 2.9%, 0.0% and 0.0%, respectively. There were
no reported deaths in the study. There were three events of
severe hypoglycemia during the 12-week treatment period (one each
in the 75 mg, 200 mg and 400 mg dose arms), and one event of
diabetic ketoacidosis (DKA) during the 12-week treatment period
(for a patient on the 400 mg dose) compared to two separate events
of DKA in one patient during the pre-randomization, placebo run-in
period of the study.
About inTandem4
The double-blind, placebo controlled, Phase 2 dose-ranging study
known as inTandem4 randomized 141 patients in the United States with type 1 diabetes on
insulin pump or multiple daily injection therapy who had an A1C
level entering the study between 7.0% and 10.0%. The four-arm
study evaluated three doses of sotagliflozin, 75 mg, 200 mg and 400
mg, each taken once daily 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 one of three doses of sotagliflozin or placebo.
Following randomization, adjustments in insulin doses could be made
when needed. The mean baseline A1C level at the time of
randomization ranged from 7.95% to 8.07% across the four arms of
the study.
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), on
September 9, 2016. Lexicon is
conducting a second pivotal Phase 3 clinical trial (inTandem2) from
which top-line results are expected in December 2016. Lexicon
is also completing a Phase 2 clinical trial in collaboration with
JDRF in young adults with type 1 diabetes, from which results are
expected prior to the end of the year. 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.
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.