THE WOODLANDS, Texas,
Aug. 15, 2017 /PRNewswire/
-- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced
today additional positive data from the pivotal Phase 3 inTandem2
study of sotagliflozin, an investigational dual SGLT1 and SGLT2
inhibitor. It was previously announced that both doses of
sotagliflozin achieved the primary endpoint of the inTandem2 study,
showing statistically significant reductions in A1C at 24 weeks in
adult patients with type 1 diabetes on a background of optimized
insulin. The new data showed that the A1C benefit was sustained
over 52 weeks as well as achievement of all secondary endpoints for
both sotagliflozin doses. These results of the inTandem2 study,
conducted primarily in Europe,
replicated results previously reported from Lexicon's Phase 3
inTandem1 study of sotagliflozin in type 1 diabetes patients,
conducted in North America.
Notably, the outcome on every secondary endpoint favored
sotagliflozin over placebo, with statistically significant results
for all six secondary endpoints for both doses:
- net benefit (proportion of patients with A1C <7.0% at Week
24 and no episode of severe hypoglycemia and no episode of diabetic
ketoacidosis (DKA);
- body weight;
- bolus insulin use;
- fasting plasma glucose (FPG);
- Diabetes Treatment Satisfaction Questionnaire status (DTSQs)
score; and
- 2-item Diabetes Distress Screening Scale (DDS2) questionnaire
score.
Systolic blood pressure (SBP) in the subset of type 1 diabetic
patients in the study with baseline hypertension (SBP ≥130 mmHg)
was also statistically significantly reduced with the 400 mg dose
compared with placebo.
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.
"InTandem2 is the second pivotal study to demonstrate
sotagliflozin's ability to durably improve both A1C and other key
measures of health such as body weight and blood pressure in
patients with type 1 diabetes. Today's results underscore
sotagliflozin's benefit/risk profile and highlight its
differentiated profile in the type 1 diabetes landscape," said
Pablo Lapuerta, M.D., Lexicon's
executive vice president and chief medical officer. "We look
forward to presenting more detailed results from the inTandem2
study at an upcoming medical conference."
"Today's results are exciting for so many people living with
type 1 diabetes," said Thomas Danne,
M.D., Head of the Diabetes Center at the Children's Hospital on the
Bult in Hannover, Germany and
primary investigator for the inTandem2 clinical trial. "The
observation that sotagliflozin significantly lowers blood glucose
and favorably affects body weight and blood pressure without an
increase in hypoglycemia strengthens the potential of the drug to
become a first-in-class therapy in the treatment paradigm for type
1 diabetes."
About inTandem2
The Phase 3 study known as inTandem2 was a double-blind,
placebo-controlled, multi-center study of 782 patients in
Europe and Israel 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 levels
after the six-week optimization period were 7.79%, 7.74% and 7.71%
for patients randomized to the placebo, 200mg and 400mg arms,
respectively.
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 258 patients in the
placebo arm, 261 patients in the 200mg dose arm and 263 patients in
the 400mg dose arm. The overall mean placebo-adjusted A1C
reduction at week 24 was 0.37% in the 200mg dose arm (p<0.001)
and 0.35% in the 400mg dose arm (p<0.001). The A1C benefit
achieved with sotagliflozin was sustained with
statistically-significant results over the full 52-week duration of
the study for both the 200 mg and 400 mg doses.
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 61.2%, 68.2% and
68.8%, respectively; the incidences of SAEs were 6.6%, 10.0% and
8.0%, respectively; and discontinuations due to AEs were 3.5%, 3.8%
and 6.8%, respectively. There were two deaths 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 13
(5.0%), 13 (5.0%), and 6 (2.3%) 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 0 (0.0%), 6 (2.3%), and 9
(3.4%) in the placebo, 200 mg and 400 mg dose arms,
respectively.
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 has exercised its option to
co-promote and to 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 first commercial product,
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.