THE WOODLANDS, Texas,
May 11, 2017 /PRNewswire/
-- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced
today additional positive data from the Phase 3 inTandem1 study. It
was previously announced that both doses of sotagliflozin achieved
the primary endpoint of the inTandem1 study, showing statistically
significant reductions in A1C at 24 weeks in patients with type 1
diabetes on a background of optimized insulin. New key findings
include meaningful benefit of sotagliflozin on body weight in
patients with type 1 diabetes and on systolic blood pressure in
hypertensive patients with type 1 diabetes. In addition, the
Company announced achievement of important secondary endpoints
including net benefit, bolus insulin use, fasting plasma glucose
and patient reported outcomes.
In a key secondary endpoint, patients taking sotagliflozin
experienced a mean reduction from baseline in body weight after 24
weeks of treatment of 1.6 kg for the 200mg dose and 2.7 kg for the
400mg dose, compared to a mean body weight gain of 0.8 kg for
patients on placebo (p<0.001 for both doses). Sustained effects
on body weight were also seen at 52 weeks.
In addition, systolic blood pressure (SBP) in the subset of type
1 diabetic patients in the study with baseline hypertension (SBP
≥130 mmHg) was reduced by 9.9 mmHg and 11.0 mmHg at week 12 when
treated with 200 mg and 400 mg of sotagliflozin, respectively,
compared to a reduction of 4.4 mmHg on placebo (p=0.017 and p=0.003
for the 200 mg and 400 mg doses, respectively).
Notably, the outcome on every secondary endpoint favored
sotagliflozin over placebo, with results for the 400 mg dose having
achieved statistical significance for all six secondary endpoints
(results for the first two secondary endpoints were also
statistically significant for the 200 mg dose):
- the proportion of patients achieving A1C <7.0% with no
episode of severe hypoglycemia or diabetic ketoacidosis ("net
benefit");
- body weight;
- bolus insulin use;
- fasting plasma glucose;
- Diabetes Treatment Satisfaction Questionnaire status (DTSQs)
score; and
- 2-item Diabetes Distress Screening Scale (DDS2) questionnaire
score.
Sotagliflozin was generally well tolerated during the 28-week
extension period, with rates of treatment-emergent adverse events
(TEAEs), serious adverse events (SAEs), and discontinuations due to
AEs that were consistent with rates seen in the initial 24-week
treatment period. The rate of severe hypoglycemia was the same or
lower for the sotagliflozin arms than placebo during the 28-week
extension period (10 patients (4.3%) for placebo, compared to 10
(4.2%) and 6 (2.5%) for sotagliflozin 200 mg and 400 mg,
respectively), and was slightly lower overall than the rate seen in
the initial 24-week treatment period. The rate of diabetic
ketoacidosis (DKA) during the 28-week extension period was slightly
higher than the rate seen in the initial 24-week treatment period
for placebo (one patient, 0.4%) and the 200 mg dose arm (6, 2.5%)
and lower for the 400 mg dose arm (3, 1.3%).
"Sotagliflozin's ability to improve both A1C and other measures
of health such as body weight and blood pressure holds promise for
addressing important areas of need in type 1 diabetes, and the
additional inTandem1 results announced today highlight the
differentiated profile of sotagliflozin in the type 1 diabetes
landscape," said Lonnel Coats,
Lexicon's president and chief executive officer. "In the coming
weeks, we look forward to the outcome of inTandem3, with its 'net
benefit' primary efficacy endpoint that measures the proportion of
patients achieving an A1C of less than 7% without a severe
hypoglycemia or DKA event. We saw favorable results on the same
endpoint in inTandem1 and inTandem2 and remain confident about
replicating these data in inTandem3."
"Type 1 diabetes is a tough disease for patients and their
providers to take care of. The potential of sotagliflozin to lower
blood glucose and favorably affect body weight and blood pressure
is tremendous," said John Buse,
M.D., Ph.D., lead investigator of inTandem1 and Professor of
Medicine, Chief of the Division of Endocrinology and Metabolism,
Director of the Diabetes Care Center, and Executive Associate Dean
for Clinical Research at the University of
North Carolina School of Medicine. "If approved,
sotagliflozin could be an important oral therapy for individuals
with type 1 diabetes while on insulin."
About inTandem1
The Phase 3 study known as inTandem1 was a double-blind,
placebo-controlled, multi-center study of 793 patients in the U.S.
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%. 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 had 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 400 mg dose arm. The overall mean placebo adjusted A1C
reduction was 0.35% in the 200 mg dose arm (p<0.001) and 0.41%
in the 400mg dose arm (p<0.001) over the initial 24-week
treatment period. The A1C benefit achieved with sotagliflozin was
sustained over the full 52-week duration of the study for both the
200 mg and 400 mg doses (p<0.001 at week 52).
Sotagliflozin was generally well tolerated during the study.
Across all three dose arms (placebo, 200mg, 400mg), over the full
52 weeks of treatment, the incidences of AEs were 80.6%, 81.7% and
79.8%, respectively; the incidences of SAEs were 7.5%, 10.3% and
11.1%, respectively; and discontinuations due to AEs were 4.1%,
4.9% and 6.5%, respectively. There was one death in the study in
the placebo arm and no deaths in either sotagliflozin
arm.
Two primary safety concerns for patients with type 1 diabetes
are severe hypoglycemia and DKA. The number of patients with severe
hypoglycemia events during the full 52 weeks of treatment was 26
(9.7%), 17 (6.5%), and 17 (6.5%) in the placebo, 200 mg and 400 mg
dose arms, respectively. The number of patients with DKA events
during the full 52 weeks of treatment was 1 (0.4%), 9 (3.4%), and
11 (4.2%) in the placebo, 200 mg and 400 mg dose arms,
respectively.
Lexicon is conducting another, similar pivotal Phase 3 clinical
trial predominantly in Europe
(inTandem2), from which top-line, primary efficacy endpoint and
safety data at 24 weeks has previously been reported and additional
data from secondary endpoints as well as pooled continuous glucose
monitoring (CGM) results from inTandem1 and inTandem2 are expected
in the third quarter of 2017. Lexicon is conducting a third, global
Phase 3 clinical trial, inTandem3, studying approximately 1,400
type 1 diabetes patients treated with sotagliflozin 400mg once
daily or placebo on a background of any insulin therapy, but
without insulin optimization prior to randomization. Top-line data
from inTandem3 is expected in the coming weeks.
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 (excluding
Japan), 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 U.S. Sanofi is responsible for all
clinical development and commercialization of sotagliflozin for the
treatment of type 2 diabetes worldwide (excluding Japan) and is solely responsible for the
commercialization of sotagliflozin for the treatment of type 1
diabetes outside the U.S. (excluding Japan).
About Lexicon Pharmaceuticals
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. In addition to its recently-launched product for
carcinoid syndrome diarrhea, XERMELO™ (telotristat ethyl), Lexicon
has a pipeline of promising drug candidates in clinical and
pre-clinical development in diabetes and metabolism and neuropathic
pain. 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
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, 2016, 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.