On November 12, 2023, Lexicon Pharmaceuticals, Inc. announced a post hoc analysis of clinical data from the SCORED trial demonstrating clinical efficacy of sotagliflozin (INPEFA®) in the treatment of heart failure and major adverse cardiovascular events as early as approximately 3 months. benefit.
“We are pleased to support research in an area of importance to heart failure clinicians and payers, and we believe the early clinical benefits of INPEFA observed in the SCORED post hoc analysis will factor into the care decisions made by these stakeholders,” said Craig. make a difference,” Granowitz, MD, PhD, Lexicon’s senior vice president and chief medical officer, said in a press release. “Avoiding stroke or myocardial infarction has significant benefits for both patients and the healthcare system, and we believe the reduction (in major adverse cardiovascular events) observed as early as approximately three months is an additional point of difference for INPEFA.”
The U.S. Food and Drug Administration (FDA) approved INPEFA® on May 26, 2023, to reduce the risk of cardiovascular death, hospitalization, or emergency department visits in patients with heart failure or type 2 diabetes, chronic kidney disease, and other cardiovascular diseases factor. INPEFA® is an oral inhibitor of 2 proteins responsible for glucose regulation, together with sodium-glucose cotransporters type 2 and type 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose reabsorption in the kidneys, and SGLT2 is responsible for glucose reabsorption in the gastrointestinal tract.
SCORED is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating sotagliflozin versus placebo in 10,584 patients with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate (eGFR) 25). The cardiovascular benefits compared to 40 ml to 60 ml per minute per 1.73 m2 of body surface area, as well as the risk of cardiovascular disease. Rahul Aggarwal, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, presented the study at the 2023 American Heart Association (AHA) Scientific Sessions in Philadelphia, Pennsylvania.
The relative risk for heart failure patients receiving INPEFA® versus placebo for patients receiving other treatments was 26% (hazard ratio (HR), 0.74; 95% CI, 0.63 – 0.88; ask < .001). At the 95-day mark after randomization, researchers found a significant and sustained reduction in the primary endpoint (hazard ratio (HR), 0.70; 95% CI, 0.50 – 0.98).
The secondary endpoint looked at major adverse cardiovascular events, with researchers finding a 23% relative risk reduction in patients treated with sotagliflozin compared with placebo (95% CI, 0.65 – 0.91; ask <.001), with a statistically significant and sustained reduction occurring 94 days after randomization (hazard ratio (HR), 0.69; 95% CI, 0.47 – 0.99).
The press release concludes by warning of adverse effects, such as:
- Risks of ketoacidosis: Media warning that INPEFA® increases the risk of ketoacidosis in patients with type 1 diabetes. People with type 2 diabetes are also at risk of ketoacidosis if they take INPEFA®. Fatal ketoacidosis has been reported in patients with type 2 diabetes taking sodium glucose transporter 2 (SGLT2 inhibitors), so Lexicon is telling people to be aware of the risk factors for ketoacidosis before taking INPEFA®.
- Risk of intravascular volume depletion: This may result in symptomatic hypotension or acute transient changes in creatinine. The risk may be increased in persons with impaired retinal function (eGFR < 60 mL/min/1.73 m2), the elderly, or patients taking loop diuretics.
- Risk of urinary tract infection: Physicians are urged to evaluate patients with INPEFA® for signs and symptoms of infection.
- Risk of hypoglycemia: This is the case when INPEFA® is taken in combination with insulin or an insulin secretagogue. In this situation, lower doses of insulin or an insulin secretagogue may be needed to reduce the risk of hypoglycemia.
- Risks of Fournier’s gangrene: This is a rare, life-threatening infection associated with diabetic patients receiving SGLT2. Physicians are advised to see patients who present with fever or malaise and pain, tenderness, erythema, or swelling in the genital or perineal area.
- Risk of genital fungal infection
The incidence of common adverse reactions for INPEFA® is > 5% were urinary tract infection, hypovolemia, diarrhea and hypoglycemia. INPEFA® is not recommended for use during the second or third pregnancy or during breastfeeding. It is also not recommended for patients with moderate or severe hepatic impairment. INPEFA® dosage does not change with age, although older patients may be at increased risk for hypovolemia or hypotension.
Volume-related adverse events such as hypotension and dizziness are increased in chronic kidney disease patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2. Treatment was discontinued if the patient's eGFR fell below 15 mL/min/1.73 m2 or if chronic dialysis was initiated.
refer to
In an analysis of clinical data, use of INPEFA® (sotagliflozin) was associated with early clinical benefit in heart failure and atherosclerotic events. Dictionary Pharmaceuticals. November 12, 2023. https://www.lexpharma.com/media-center/news/2023-11-12-inpefa-r-sotagliflozin-use-linked-with-early-clinical-benefit-in-heart-failure – and clinical data analysis Atherosclerotic events in . Accessed: November 13, 2023.