New Data Relating to Sotagliflozin to be Presented at the American Society of Nephrology (ASN) Kidney Week 2023 Annual Meeting

Presentations from four Lexicon-sponsored studies will highlight data supporting current and potential future use of sotagliflozin

INPEFA® (sotagliflozin) recently approved by FDA for treatment of heart failure

THE WOODLANDS, Texas, Oct. 30, 2023 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that analyses of clinical study results relating to sotagliflozin, as well as data from a Lexicon-supported scientific study of patients hospitalized with heart failure who also had chronic kidney disease (CKD), will be presented during the American Society of Nephrology (ASN) Kidney Week Annual Meeting, November 2-5, 2023, at the Pennsylvania Convention Center in Philadelphia, PA.

Details of the presentations are as follows:

• Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and Chronic Kidney Disease [TH-PO1144] – Late-Breaking Clinical Trial poster presentation, Thursday, November 2, 10:00 a.m. – 12:00 p.m. ET, Exhibit Hall, Pennsylvania Convention Center, presented by Vikas Sridhar, M.D., University of Toronto
• Sotagliflozin and Kidney and Cardiorenal Outcomes in SCORED [FR-OR45] – an oral presentation, Friday, November 3, 5:06 - 5:15 p.m. ET, Room 119, Pennsylvania Convention Center, presented by David Cherney, M.D., Ph.D., University Health Network, University of Toronto
• Effects of Sotagliflozin on Anemia in Patients with Type 2 Diabetes (T2D) and Stages 3 and 4 CKD [SA-PO474] – a poster presentation, Saturday, November 4, 10:00 a.m. – 12:00 p.m. ET, Exhibit Hall, Pennsylvania Convention Center, presented by Vikas Sridhar, M.D., University of Toronto
• Concordance Between Laboratory- and ICD-10 Code-Defined Stages of CKD Among Patients Hospitalized with Heart Failure in a Large US Integrated Health System [SA-PO1118] – a poster presentation, Saturday, November 4, 10:00 a.m. – 12:00 p.m. ET, Exhibit Hall, Pennsylvania Convention Center, presented by Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer

“Across the various data presented, we seek to address the challenges and complications of diabetes and chronic kidney disease,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. “We are continuing to study the clinical benefits of sotagliflozin and will work diligently to inform broadly of the scientific evidence demonstrated.”

On May 26, 2023, the U.S. Food and Drug Administration approved INPEFA® (sotagliflozin), a once-daily oral tablet, 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.

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 treat diseases safely and effectively. Lexicon has advanced multiple medicines to market and has a pipeline of promising drug candidates in heart failure, neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com.

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 reabsorption by the kidney and SGLT1 is responsible for glucose absorption in the gastrointestinal tract. INPEFA has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients.

INDICATION

INPEFA 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 any component.

Warnings and Precautions:

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.

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