Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced a new
post-hoc analysis of clinical data showing that INPEFA®
(sotagliflozin), a dual oral inhibitor of SGLT2 and SGLT1, reduced
the risk of heart failure-related events across a diverse
population of patients, including patients with preserved ejection
fraction (HFpEF). Researchers noted that INPEFA appeared to be
particularly effective in reducing the risk of heart failure events
in patients with an obesity-related HFpEF phenotype. These
findings, based on a pooled, patient-level analysis of data from
the SOLOST-WHF and SCORED pivotal clinical trials, were presented
today at the Annual Congress of the Heart Failure Association of
the European Society of Cardiology (ESC) in Lisbon, Portugal.
Obesity and type 2 diabetes (T2D), along with a
growing aging population, is contributing to the escalating
prevalence of HFpEF. Recent data published in journals of the
American College of Cardiology and the American Heart Association
suggest that individuals with an obesity-related HFpEF phenotype
represent a distinctive and clinically significant subgroup from
those with standard HFpEF phenotype. This new analysis assessed the
impact of obesity, along with sex and age, on the effects of INPEFA
on the primary composite endpoint of cardiovascular (CV) death and
heart failure (HF) events in patients with left ventricular
ejection fraction (LVEF) ≥ 50%. Previously, SOLOIST-WHF and SCORED
data demonstrated that INPEFA, a dual oral inhibitor of SGLT2 and
SGLT1, is effective in reducing the risk of CV death and HF-related
outcomes across the LVEF range.
Data from a total of 1,932 patients were
included in the analysis (mean age: 69.9 years, mean BMI: 34.1
kg/m²; mean HbA1c:8.5%). In this population, 18.1% of patients
experienced a primary endpoint event. Males and females
demonstrated comparable event rates, 18.3% and 18.0% respectively;
however, older age (< 65: 10.9% vs. ≥ 65years: 20.3%) and higher
BMI (< 30 kg/m²: 16.6% vs. ≥ 30 kg/m²: 18.7%) were associated
with an increased number of patients at risk for primary endpoint
events.
Within the subgroup characterized by higher BMI,
INPEFA therapy resulted in a favorable response for patients with
BMI ≥ 30 kg/m² (p-value for interaction 0.038). Researchers also
noted that both sex and age subgroups had a consistent response to
INPEFA (p-value for interaction 0.818 and 0.393, respectively).
“This analysis underscores the importance of
identifying patient risk factors such as age, sex, and obesity in
patients with HFpEF and adds to the body of evidence
differentiating INPEFA as a dual inhibitor of SGLT1 and SGLT2,”
said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president
and chief medical officer. “Additionally, today’s data presentation
further highlights the benefits of INPEFA in reducing the risk of
heart failure-related events across a wide range of patients with
HFpEF, including in patients with an obesity-related HFpEF
phenotype.”
About
INPEFA® (sotagliflozin)Discovered
using Lexicon’s unique approach to gene science,
INPEFA® (sotagliflozin) is an oral inhibitor of two proteins
responsible for glucose regulation known as sodium-glucose
cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible
for glucose and sodium reabsorption by the kidney and SGLT1 is
responsible for glucose and sodium absorption in the
gastrointestinal tract. Sotagliflozin has been studied in multiple
patient populations encompassing heart failure, diabetes, and
chronic kidney disease in clinical studies involving approximately
20,000 patients.
INDICATIONINPEFA is indicated to reduce the
risk of cardiovascular death, hospitalization for heart failure,
and urgent heart failure visit in adults with:
- heart failure or
- type 2 diabetes mellitus, chronic kidney disease, and other
cardiovascular risk factors
IMPORTANT SAFETY INFORMATION
Dosing: Assess renal function and volume
status and, if necessary, correct volume depletion prior to
initiation of INPEFA. INPEFA dosing for patients with decompensated
heart failure may begin when patients are hemodynamically stable,
including when hospitalized or immediately upon discharge.
Contraindications: INPEFA is
contraindicated in patients with hypersensitivity to INPEFA or any
of its components.
Ketoacidosis: INPEFA increases the risk of
ketoacidosis in patients with type 1 diabetes mellitus (T1DM). Type
2 diabetes Mellitus (T2DM) and pancreatic disorders are also risk
factors. The risk of ketoacidosis may be greater with higher doses.
There have been postmarketing reports of fatal events of
ketoacidosis in patients with type 2 diabetes using sodium glucose
transporter 2 (SGLT2) inhibitors. Before initiating INPEFA, assess
risk factors for ketoacidosis. Consider ketone monitoring in
patients with T1DM and consider ketone monitoring in others at risk
for ketoacidosis and educate patients on the signs/symptoms of
ketoacidosis. Patients receiving INPEFA may require monitoring and
temporary discontinuation of therapy in clinical situations known
to predispose to ketoacidosis. INPEFA is not indicated for glycemic
control.
Assess patients who present with signs and symptoms of metabolic
acidosis or ketoacidosis, regardless of blood glucose level. If
suspected, discontinue INPEFA, evaluate, and treat promptly.
Monitor patients for resolution of ketoacidosis before restarting
INPEFA.
Volume Depletion: INPEFA can cause
intravascular volume depletion which may sometimes manifest as
symptomatic hypotension or acute transient changes in creatinine.
There have been post-marketing reports of acute kidney injury, some
requiring hospitalization and dialysis, in patients with type 2
diabetes mellitus receiving SGLT2 inhibitors. Patients with
impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly
patients, or patients on loop diuretics may be at increased risk
for volume depletion or hypotension. Before initiating INPEFA in
patients with one or more of these characteristics, assess volume
status and renal function, and monitor for signs and symptoms of
hypotension during therapy.
Urosepsis and Pyelonephritis: Treatment
with SGLT2 inhibitors, including INPEFA, increases the risk for
urinary tract infections. Serious urinary tract infections
including urosepsis and pyelonephritis requiring hospitalization
have been reported. Evaluate patients for signs and symptoms of
urinary tract infections and treat promptly.
Hypoglycemia with Concomitant Use with Insulin and
Insulin Secretagogues: Insulin and insulin
secretagogues are known to cause hypoglycemia. INPEFA may increase
the risk of hypoglycemia when combined with insulin or an insulin
secretagogue. Therefore, a lower dose of insulin or insulin
secretagogue may be required to minimize the risk of hypoglycemia
when used with INPEFA.
Necrotizing Fasciitis of the Perineum (Fournier’s
Gangrene): Reports of Fournier’s Gangrene, a rare but
serious and life-threatening necrotizing infection requiring urgent
surgical intervention, have been identified in post-marketing
surveillance in patients with diabetes mellitus receiving SGLT2
inhibitors. Assess patients who present with pain, tenderness,
erythema, or swelling in the genital or perineal area, along with
fever or malaise. If suspected, start treatment immediately with
broad-spectrum antibiotics and, if necessary, surgical debridement.
Discontinue INPEFA, closely monitor patient signs and symptoms, and
provide appropriate alternative therapy for heart failure.
Genital Mycotic Infections: INPEFA
increases the risk of genital mycotic infections. Monitor and treat
as appropriate.
Urinary Glucose Test and 1,5-anhydroglucitol (1,5-AG)
Assay: these are not reliable for patients taking
SGLT2 inhibitors. Use alternative testing methods to monitor
glucose levels.
Common Adverse Reactions: the most
commonly reported adverse reactions (incidence ≥ 5%) were urinary
tract infection, volume depletion, diarrhea, and hypoglycemia.
Drug Interactions:
- Digoxin: Monitor patients appropriately
as there is an increase in the exposure of digoxin when
coadministered with INPEFA 400 mg.
- Uridine 5'-diphospho-glucuronosyltransferase (UGT)
Inducer: The coadministration of rifampicin, an
inducer of UGTs, with sotagliflozin resulted in a decrease in the
exposure of sotagliflozin.
- Lithium: Concomitant use of an SGLT2
inhibitor with lithium may decrease serum lithium concentrations.
Monitor serum lithium concentration more frequently during INPEFA
initiation and with dosage changes.
Use in Specific Populations:
- Pregnancy and Lactation: INPEFA is not
recommended during the second and third trimesters of pregnancy,
nor while breastfeeding.
- Geriatric Use: No INPEFA dosage change is
recommended based on age. No overall differences in efficacy were
detected between these patients and younger patients, and other
reported clinical experience has not identified differences in
responses between the elderly and younger patients, but greater
sensitivity of some older individuals cannot be ruled out. Elderly
patients may be at increased risk for volume depletion adverse
reactions, including hypotension.
- Renal Impairment: INPEFA was evaluated in
patients with chronic kidney disease (eGFR 25 to
60 mL/min/1.73 m2) and in patients with heart failure with
eGFR < 60 mL/min/1.73 m2. The safety profile of INPEFA
across eGFR subgroups in these studies was consistent with the
known safety profile. There was an increase in volume-related
adverse events (e.g., hypotension, dizziness) in patients with eGFR
< 30 mL/min/1.73m2 relative to the overall safety
population. Efficacy and safety studies with INPEFA did not enroll
patients with an eGFR less than 25 mL/min/1.73 m2 or on
dialysis. After starting therapy in the studies, patients were
discontinued if eGFR fell below 15 mL/min/1.73 m2 or were
initiated on chronic dialysis.
- Hepatic Impairment: INPEFA is not
recommended in patients with moderate or severe hepatic
impairment.
Click here for full Prescribing Information.
https://www.lexpharma.com/inpefa-US-PI.pdf
About Lexicon PharmaceuticalsLexicon is a
biopharmaceutical company with a mission of pioneering medicines
that transform patients’ lives. Through the Genome5000™ program,
Lexicon’s unique genomics target discovery platform, 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 treat disease safely and
effectively. Lexicon has commercially launched one of these
medicines, INPEFA® (sotagliflozin) in the United States, and
has a pipeline of other promising drug candidates in discovery and
clinical and preclinical development in neuropathic pain, diabetes
and metabolism 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 financial
position and long-term outlook on its business, growth and future
operating results, discovery, development and commercialization 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 Lexicon’s ability
to meet its capital requirements, successfully commercialize INPEFA
in heart failure, conduct preclinical and clinical development and
obtain necessary regulatory approvals of sotagliflozin (in other
indications), LX9211, LX9851 and its other 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 products and 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, 2023 and other subsequent disclosure documents 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 Investor Inquiries:Lisa DeFrancescoLexicon
Pharmaceuticals, Inc.lexinvest@lexpharma.com
For Media Inquiries:Alina CocuzzaLexicon
Pharmaceuticals, Inc.acocuzza@lexpharma.com
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