Clinical Data on the Impact of Sotagliflozin on Stroke and Heart Attack Risk Among Four Lexicon-Sponsored Presentations at the American College of Cardiology 73rd Annual Scientific Session & Expo

Rhea-AI Summary

Lexicon Pharmaceuticals, Inc. (LXRX) announces four data presentations on sotagliflozin at the ACC 73rd Annual Scientific Session. The presentations include reducing stroke events in patients with type 2 diabetes, CKD, and high CV risk, modulation of glucose transport and inflammatory proteins, inhibition of clotting potential, and a study on heart failure medication prescriptions. Sotagliflozin showed a 34% reduction in all-cause stroke risk, 32% reduction in ischemic stroke risk, and favorable actions in endothelial cells. The findings provide insights into sotagliflozin's mechanism of action and potential for cardiovascular protection.

Positive

• Sotagliflozin demonstrated a 34% reduction in all-cause stroke risk in patients with type 2 diabetes, CKD, and high CV risk.
• The drug also showed a 32% reduction in the risk of ischemic stroke compared to the placebo group.
• Sotagliflozin modulated the expression of proteins linked to glucose transport and vasodilation in human endothelial cells, providing insights into its mechanism of action.
• The drug inhibits platelet activation by targeting SGLT1 and SGLT2, potentially reducing the risk of stroke and MI in patients with type 2 diabetes and CKD.
• The study on heart failure medication prescriptions highlighted opportunities to improve guideline-directed medical therapy for patients with HF, emphasizing the need to address care gaps by sex and age.

Negative

• None.

Insights

Cardiologist

The recent findings on sotagliflozin, particularly its efficacy in reducing stroke events in high-risk patients, add a significant chapter to cardiovascular pharmacotherapy. The reported 34% risk reduction in all-cause stroke and 32% in ischemic stroke is noteworthy, as stroke prevention is a pivotal aspect of managing type 2 diabetes and chronic kidney disease. These conditions often coexist and synergistically elevate cardiovascular risk, making effective interventions essential.

From a cardiological standpoint, the dual inhibition mechanism of sotagliflozin, targeting both SGLT2 and SGLT1, represents an innovative approach. SGLT2 inhibitors have already been recognized for their cardiovascular benefits and the additional SGLT1 inhibition could offer a broader therapeutic impact. The modulation of glucose transport and inflammatory proteins in endothelial cells, as well as the inhibition of platelet activation, suggest potential for sotagliflozin to address atherothrombosis beyond glycemic control.

For patients, these findings may translate to improved clinical outcomes and quality of life. However, it's essential to consider the long-term safety profile of sotagliflozin, given the complex nature of its patient population. Ongoing surveillance and post-marketing studies will be important to monitor adverse effects and ensure the drug's net clinical benefit.

Healthcare Economist

From an economic perspective, the approval and subsequent utilization of sotagliflozin for heart failure and cardiovascular risk reduction could have substantial implications for healthcare costs and resource allocation. Stroke is a leading cause of disability and incurs significant healthcare expenses, not only due to the acute management but also from long-term rehabilitation and care needs.

The potential cost savings from reduced stroke incidence and severity, as well as the decrease in hospitalizations for heart failure, could be significant. However, these benefits must be weighed against the cost of sotagliflozin, especially as healthcare systems grapple with budget constraints and the imperative to maximize the cost-effectiveness of interventions.

Moreover, disparities in the initiation of guideline-directed medical therapies, as highlighted by the gender and age differences in prescription patterns, suggest that there may be systemic inefficiencies and biases in treatment approaches. Addressing these care gaps could lead to more equitable and effective management of heart failure, further enhancing the economic value of interventions like sotagliflozin.

Pharmaceutical Market Analyst

The FDA's approval of sotagliflozin and its demonstrated efficacy in reducing cardiovascular events place Lexicon Pharmaceuticals in a favorable position within the cardiovascular drug market. As a first-in-class dual SGLT1/2 inhibitor, sotagliflozin could capture a significant market share, especially among patients with type 2 diabetes and chronic kidney disease who are at high cardiovascular risk.

The pharmaceutical market for diabetes and heart failure is highly competitive and differentiation is key to success. Sotagliflozin's dual mechanism offers a unique selling point. However, market penetration will depend on factors such as pricing, insurance coverage and the ability of Lexicon to communicate the drug's benefits to clinicians and patients effectively.

It's also important to monitor the competitive landscape for potential new entrants or advancements in alternative therapies that could impact sotagliflozin's market position. Strategic partnerships, continued investment in research and attention to post-marketing safety data will be essential for sustaining growth and addressing the needs of a diverse patient population.

THE WOODLANDS, Texas, March 25, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that four data presentations related to sotagliflozin, an inhibitor of two sodium glucose transport proteins (SGLT2 and SGLT1), will be delivered during the American College of Cardiology 73rd Annual Scientific Session & Expo being held April 6 - 8, 2024 in Atlanta, Georgia, including results from a post-hoc evaluation of the efficacy of sotagliflozin in reducing stroke events in patients with type 2 diabetes, chronic kidney disease (CKD), and high cardiovascular (CV) risk in the SCORED Phase 3 clinical trial.

“Following FDA’s 2023 approval of INPEFA^® (sotagliflozin) for heart failure (HF), researchers are adding to the overall scientific understanding of sotagliflozin, including clinical evidence of its ability to reduce the risk of stroke and myocardial infarction (MI), or heart attack,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer.

Details of the presentations are as follows:

• Sotagliflozin Reduces Stroke Outcomes in Patients with Diabetes and Chronic Kidney Disease – a moderated poster presentation, Monday, April 8, 12:15 - 12:25 p.m. ET, Theater 8‚ presented by Rahul Aggarwal, M.D., Icahn School of Medicine at Mount Sinai, New York, New York
  
  Study researchers evaluated the efficacy of sotagliflozin in reducing all-cause and cause-specific stroke outcomes among patients with type 2 diabetes, CKD, and high CV risk. In a post-hoc analysis of data from the 10,584 patients in the SCORED Phase 3 clinical trial, 213 all-cause stroke events occurred, including 29 (13.6%) fatal events. Sotagliflozin reduced the risk of all-cause stroke by 34%, with 1.2 events per 100 patient-years in the sotagliflozin group and 1.8 events per 100 patient-years in the placebo group. Similarly, sotagliflozin reduced the risk of ischemic stroke by 32%, with 0.8 events per 100 patient-years in the sotagliflozin group and 1.2 events per 100 patient-years in the placebo group.
  
  Click here to access additional study details in the online abstract.

• Sotagliflozin, a Dual SGLT 1 and 2 Inhibitor, Modulated Expression of Glucose Transport and Inflammatory Proteins in Endothelial Cells following Angiotensin II Stimulation – a poster presentation, Sunday, April 7, 1:15 – 2:00 p.m. ET, 1425-157, Hall B4-5, presented by Preston Mason, Ph.D. MBA, Elucida Research, Beverly, Massachusetts
  
  Study researchers found that sotagliflozin modulated expression of proteins linked to the Akt signaling pathway, glucose transport and vasodilation in human endothelial cells   exposed to an inflammatory stimulus in vitro. The favorable endothelial cell actions of sotagliflozin during inflammation add to the body of knowledge of sotagliflozin’s mechanism of action and are consistent with the reduced atherothrombotic risk demonstrated in outcome trials.
  
  Click here to access additional study details in the online abstract.

• Sotagliflozin, a First-in-Class SGLT1/2 Inhibitor, Inhibits Clotting Potential in the Vessel via Inhibition of Platelet Activation, Integrin Activation, and Aggregation in Human Platelets – a moderated poster presentation, Sunday, April 7, 11:30 - 2:40 a.m. ET, Theater 5‚ presented by Livia Stanger, Ph.D. Candidate, University of Michigan, Ann Arbor, Michigan
  
  Study researchers found that sotagliflozin inhibits platelet activation through simultaneously targeting SGLT1 and SGLT2. These findings provide insight into the potential mechanism by which sotagliflozin impacts stroke and MI risk in patients with type 2 diabetes and CKD and provides a basis for further studies to explore the role of sotagliflozin for CV protection in patients at increased risk for ischemic events.
  
  Click here to access study details in the online abstract.

• Temporal Shift in Heart Failure Medications Prescribed to Hospitalized Patients According to Sex and Age. Results from Two Large US Integrated Health Systems – a poster presentation, Sunday, April 7, 9:15 – 10:00 a.m. ET, 1343-121, Hall B4-5, presented by Mario Enrico Canonico, M.D., Ph.D., CPC Clinical Research, University of Colorado, Aurora, Colorado
  
  Study researchers found that substantial opportunity exists to further improve the prescription of guideline-directed medical therapy (GDMT) for patients with HF. Differences in timing of initiation of these therapies by sex and age highlight the need to evaluate care gaps by these and other determinants of health.
  
  Click here to access additional study details in the online abstract.

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 <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.

Safe Harbor Statement

This press release contains “forward-looking statements,” including statements relating to the therapeutic and commercial potential, research and clinical development and regulatory status of INPEFA^® (sotagliflozin). In addition, this press release also contains forward looking statements relating to Lexicon’s financial position and 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 Lexicon’s ability to meet its capital requirements, successfully commercialize INPEFA in heart failure on the timeline and/or at the prices currently contemplated or at all, conduct preclinical and clinical development and obtain necessary regulatory approvals of INPEFA (in other indications), LX9211 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 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 DeFrancesco
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com

For Media Inquiries:
Alina Cocuzza
Lexicon Pharmaceuticals, Inc.
acocuzza@lexpharma.com

FAQ

What were the main findings of the study on sotagliflozin's impact on stroke risk?

The study showed a 34% reduction in all-cause stroke risk and a 32% reduction in ischemic stroke risk in patients with type 2 diabetes, CKD, and high CV risk.

How does sotagliflozin modulate the expression of proteins in endothelial cells?

Sotagliflozin modulates the expression of proteins linked to glucose transport, vasodilation, and the Akt signaling pathway in human endothelial cells.

What is the potential mechanism by which sotagliflozin impacts stroke and MI risk?

Sotagliflozin inhibits platelet activation by targeting SGLT1 and SGLT2, potentially reducing the risk of stroke and MI in patients with type 2 diabetes and CKD.

What did the study on heart failure medication prescriptions reveal?

The study highlighted opportunities to improve guideline-directed medical therapy for patients with heart failure, emphasizing the need to address care gaps by sex and age.