Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), today announced that
both the SOLOIST and SCORED Phase 3 studies achieved their primary
endpoints by demonstrating statistically significant reductions in
total cardiovascular deaths, hospitalizations for heart failure and
urgent heart failure visits in patients treated with sotagliflozin
as compared with placebo.
In the SOLOIST study, the primary endpoint was
achieved with a hazard ratio (HR) of 0.67 (p<0.001) in people
with type 2 diabetes and a recent hospitalization for worsening
heart failure. In the SCORED study, the primary endpoint was
achieved with a hazard ratio of 0.74 (p<0.001) in people with
type 2 diabetes and chronic kidney disease with an estimated
glomerular filtration rate (eGFR) of 25 to 60 ml/minute per 1.73
m² of body-surface area.
The key results from SOLOIST and SCORED were
presented today at the Late-Breaking Science Session of the
American Heart Association (AHA) Scientific Sessions 2020 and
simultaneously published in The New England Journal of Medicine
(NEJM) in two separate articles titled: “Sotagliflozin in Patients
with Diabetes and Recent Worsening Heart Failure” and
“Sotagliflozin in Patients with Diabetes and Chronic Kidney
Disease.” The articles may be accessed at www.nejm.org.
“Cardiovascular disease continues to be a
leading cause of death in people with type 2 diabetes,” said Deepak
L. Bhatt, M.D., M.P.H., executive director of Interventional
Cardiovascular Programs at Brigham and Women's Hospital and a
professor of medicine at Harvard Medical School and study chair and
lead author for the NEJM publications of the SOLOIST and SCORED
results. “SOLOIST demonstrates that early, in-hospital initiation
of sotagliflozin in patients with worsening heart failure
significantly reduces subsequent cardiovascular events, an effect
that was consistent across groups with heart failure with reduced
ejection fraction (HFrEF) and heart failure with preserved ejection
fraction (HFpEF). SCORED demonstrates that sotagliflozin
significantly reduces heart failure events in a patient population
with stage 3 and 4 chronic kidney disease and cardiovascular risk.
Both studies add to the evidence that SGLT2 inhibition should be
standard of care in heart failure, and the SCORED data reflecting a
reduction in myocardial infarction and stroke and better glucose
control in CKD patients suggest potential benefits from the dual
SGLT1 and SGLT2 mechanism of this particular agent.”
Key SOLOIST Phase 3 Study
Results
SOLOIST was a multi-center, randomized,
double-blinded, placebo-controlled Phase 3 study evaluating the
cardiovascular efficacy of sotagliflozin versus placebo when added
to standard of care in 1,222 patients with type 2 diabetes who had
recently been hospitalized for worsening heart failure. The primary
endpoint was the total number of events comprised of deaths from
cardiovascular causes, hospitalizations for heart failure, and
urgent visits for heart failure in patients starting treatment with
200 mg sotagliflozin once daily compared with placebo, with dosing
initiated either before or within 3 days of hospital discharge.
The first dose of sotagliflozin or placebo was
administered prior to hospital discharge in 48.8% of the patients
and a median of two days after discharge in 51.2% of the patients,
with the benefits of sotagliflozin being consistent between those
prespecified subgroups of patients. The initial 200 mg once daily
dose of sotagliflozin was increased to 400 mg once daily if
unacceptable side effects did not occur.
Treatment with sotagliflozin resulted in a
significantly lower total number of cardiovascular deaths, heart
failure hospitalizations and urgent visits as compared to placebo.
A total of 600 primary endpoint events occurred in the study, with
245 events in the sotagliflozin treated group and 355 events in the
placebo group. There were 51.0 primary endpoint events per 100
patient-years in the sotagliflozin treated group as compared to
76.3 events per 100 patient-years in the placebo group (HR=0.67;
95% confidence interval [CI]=0.52 to 0.85; p<0.001). There were
10.6 events of cardiovascular death per 100 patient-years in the
sotagliflozin treated group as compared to 12.5 events per 100
patient-years in the placebo group (HR=0.84; 95% CI=0.58 to 1.22;
p=0.36).
Of note, effects on the primary endpoint were
consistent among patients suffering from heart failure with reduced
ejection fraction (HFrEF) and heart failure with preserved ejection
fraction (HFpEF), with a hazard ratio of 0.72 (95% CI=0.56 to 0.94)
in patients with a left ventricular ejection fraction (LVEF) of
less than 50% and a hazard ratio of 0.48 (95% CI=0.27 to 0.86) in
patients with a LVEF of greater than or equal to 50%.
Serious adverse events that led to
discontinuation of study drug, as determined by investigators,
occurred in 3.0% (n=18) of the patients in the sotagliflozin
treated group and in 2.8% (n=17) of the patients in the placebo
group. Based on investigator reported events, the most common
adverse events of special interest included hypotension (6.0% on
sotagliflozin versus 4.6% on placebo), urinary tract infections
(4.8% on sotagliflozin versus 5.1% on placebo), acute kidney injury
(4.1% on sotagliflozin versus 4.4% on placebo), and diarrhea (6.1%
on sotagliflozin versus 3.4% on placebo). Among other adverse
events of interest, in SOLOIST, genital mycotic infections (0.8% on
sotagliflozin vs. 0.2% on placebo) were infrequent, severe
hypoglycemia (1.5% on sotagliflozin vs. 0.3% on placebo) was more
common in the sotagliflozin treated group and diabetic ketoacidosis
(0.3% on sotagliflozin vs. 0.7% on placebo) was similar between
treatment groups.
The SOLOIST study was originally designed with a
primary endpoint of the first occurrence of death from
cardiovascular causes or hospitalization for heart failure, as
determined by independent adjudication, but was modified in
connection with the early close out of the study to include urgent
heart failure visits and reflect the total number of events, as
determined by investigators, in order to enhance the statistical
power of the comparison. The specification of the primary endpoint
based on total events was implemented without any awareness of the
study outcomes or study-group assignments and without information
from an interim analysis.
The results for first occurrence of
cardiovascular death or hospitalization for heart failure (HR=0.71;
95% CI=0.57 to 0.89; p=0.003) based on investigator reported events
were consistent with those of the modified primary endpoint.
Key SCORED Phase 3 Study
Results
SCORED was a multi-center, randomized,
double-blinded, placebo-controlled Phase 3 study evaluating the
cardiovascular efficacy of sotagliflozin versus placebo when added
to standard of care in 10,584 patients with type 2 diabetes,
chronic kidney disease with eGFR of 25 to 60 ml per minute per 1.73
m² of body-surface area, and risks for cardiovascular disease.
The primary endpoint was the total number of deaths from
cardiovascular causes, hospitalizations for heart failure, and
urgent visits for heart failure in patients treated with
sotagliflozin compared with placebo. The initial 200 mg once daily
dose of sotagliflozin was increased to 400 mg once daily if
unacceptable side effects did not occur.
Treatment with sotagliflozin resulted in a
significantly lower total number of cardiovascular deaths, heart
failure hospitalizations and urgent visits as compared to placebo.
A total of 930 primary endpoint events occurred in the study, with
400 events in the sotagliflozin treated group and 530 events in the
placebo group. There were 5.6 primary endpoint events per 100
patient-years in the sotagliflozin treated group as compared to 7.5
events per 100 patient-years in the placebo group (HR=0.74; 95%
CI=0.63 to 0.88; p<0.001). There were 2.2 events of
cardiovascular death per 100 patient-years in the sotagliflozin
treated group as compared to 2.4 events per 100 patient-years in
the placebo group (HR=0.90; 95% CI=0.73 to 1.12; p=0.35).
Of note, over the course of the study, the data
showed an average reduction in hemoglobin A1c of 0.56% in the
sotagliflozin treated group as compared to a reduction of 0.25% in
the placebo group in patients with severe chronic kidney disease,
eGFR less than 30 ml per minute per 1.73 m² of body-surface
area (p<0.001). In patients with moderate chronic kidney
disease, eGFR greater than or equal to 30 ml per minute per 1.73
m² of body-surface area, the data showed an average reduction
in hemoglobin A1c of 0.60% in the sotagliflozin treated group as
compared to a reduction of 0.17% in the placebo group
(p<0.001).
Serious adverse events that led to
discontinuation of study drug, as determined by investigators,
occurred in 2.1% (n=112) of the patients in the sotagliflozin
treated group and in 1.8% (n=94) of the patients in the placebo
group. Based on investigator reported events, the most common
adverse events of special interest included urinary tract
infections (11.5% on sotagliflozin versus 11.1% on placebo),
diarrhea (8.5% on sotagliflozin versus 6.0% on placebo), volume
depletion (5.3% on sotagliflozin versus 4.0% on placebo), bone
fractures (2.1% on sotagliflozin versus 2.2% on placebo), and
genital mycotic infections (2.4% on sotagliflozin versus 0.9% on
placebo). Among other adverse events of interest, diabetic
ketoacidosis (0.6% on sotagliflozin vs. 0.3% on placebo) was more
common in the sotagliflozin treated group and severe hypoglycemia
(1.0% on sotagliflozin vs. 1.0% on placebo) was similar between
treatment groups.
The SCORED study was originally designed with
co-primary endpoints, assessed in time-to-event analyses, of the
first occurrence of a major adverse cardiovascular event (defined
as death from cardiovascular causes, nonfatal myocardial
infarction, or nonfatal stroke, or 3-point MACE) and the first
occurrence of death from cardiovascular causes or hospitalization
for heart failure, as determined by independent adjudication, but
were modified in connection with the early close out of the study
to include urgent heart failure visits and reflect the total number
of events, as determined by investigators, in order to enhance the
statistical power of the comparison. The specification of the
primary endpoint based on total events was implemented without any
awareness of the study outcomes or study-group assignments and
without information from an interim analysis.
In a time-to-event analysis, applying the
original co-primary endpoints based on investigator reported
events, the results for both the first occurrence of a MACE event
(HR=0.84; 95% CI=0.72 to 0.99; p=0.035) and the first occurrence of
death from cardiovascular causes or hospitalization for heart
failure (HR=0.78; 95% CI=0.66 to 0.91; p=0.001) were consistent
with those of the modified primary endpoint.
About Sotagliflozin
Discovered using Lexicon’s unique approach to
gene science, sotagliflozin is an 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 is approved in the European Union (EU) for use as an
adjunct to insulin therapy to improve blood sugar (glycemic)
control in adults with type 1 diabetes with a body mass index ≥ 27
kg/m², who could not achieve adequate glycemic control despite
optimal insulin therapy, but has not yet been commercially
launched.
About Lexicon
Pharmaceuticals
Lexicon is a biopharmaceutical company with a
mission of pioneering medicines that transform patients’ lives.
Through its Genome5000™ program, Lexicon scientists studied the
role and function of nearly 5,000 genes and 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 advanced
one of these medicines to market and has a pipeline of promising
drug candidates in discovery and clinical and preclinical
development in diabetes and metabolism, neuropathic pain and other
indications. For additional information, please visit
www.lexpharma.com.
Safe Harbor Statement
This press release contains “forward-looking
statements,” including statements relating to Lexicon’s clinical
development of sotagliflozin and the clinical development and
therapeutic and commercial potential of sotagliflozin. In addition,
this press release also contains forward looking statements
relating to Lexicon’s financial position, long term outlook on its
business, 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 the FDA and other regulatory authorities
may not grant regulatory approval of sotagliflozin, 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 LX9211 and its other
potential drug candidates on its anticipated timelines, 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, 2019, 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.
For Inquiries:
Chas SchultzExecutive Director, Corporate
Communications and Investor RelationsLexicon Pharmaceuticals(281)
863-3421cschultz@lexpharma.com
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