US FDA approves Lexicon Pharma's Inpefa for treatment of heart failure

Lexicon Pharmaceuticals, Inc. announced that the FDA has approved Inpefa (sotagliflozin), a once-daily oral tablet, to reduce the risk of cardiovascular death, hospitalisation 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. The broad label includes heart failure patients with any level of left ventricular ejection fraction (LVEF), including preserved and diminished ejection fraction, as well as patients with or without diabetes.

"The approval of Inpefa, along with the breadth of the label, is a major milestone in Lexicon's path to fulfilling its mission of pioneering medicines that transform patients' lives," stated Lexicon CEO Lonnel Coats. "We expect this important innovation to be commercially available in the US market by the end of June 2023." The approval is based on two randomized, double-blind, placebo-controlled phase 3 cardiovascular outcomes studies of Inpefa in patients with heart failure or at risk of heart failure.

Together, SOLOIST-WHF (Worsening Heart Failure) and SCORED enrolled almost 12,000 patients. Results from SOLOIST-WHF showed that Inpefa significantly reduced risk of the composite of hospitalizations for heart failure, urgent visits for heart failure, and cardiovascular death by 33% compared to placebo in patients who had been recently hospitalized for worsening heart failure. Inpefa is an inhibitor of both sodium-glucose co-transporter type 2 (SGLT2) and type 1 (SGLT1).

The SGLT inhibitor class was recommended as first-line treatment for heart failure by the American Heart Association (AHA), the American College of Cardiology (ACC), and the Heart Failure Society of America (HFSA) in their joint 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. An April 2023 ACC expert consensus statement highlighted the benefit of SGLT inhibitors as part of Guideline-Directed Medical Therapy (GDMT) in patients with heart failure with preserved ejection fraction (HFpEF). According to the ACC expert consensus statement, SGLT2 inhibitors should be initiated in all individuals with HFpEF who are stable during hospitalization and have no patient population contraindications. About 6.7 million Americans suffer from heart failure, with the prevalence expected to rise to 8.0 million by 2030. Heart failure is the leading cause of hospitalizations for individuals aged 65 and older, triggering approximately 1.3 million hospitalizations a year.

Patients with heart failure are at highest risk of a heart failure event in the first 30 days post-discharge, with 7% dying and 25% being rehospitalized within one month. “Based on outcomes observed in the SOLOIST-WHF study, initiating treatment with Inpefa prior to or upon hospital discharge has the potential to reduce the burden of readmissions on patients, caregivers, providers, and health systems,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. “With today’s FDA approval, Inpefa is now a valuable option for physicians to consider when treating patients transitioning out of the hospital and working to break the cycle of repeated hospitalizations.” Lexicon expects Inpefa to be available by the end of June 2023.

The company plans to set the medicine’s wholesale acquisition cost comparable to existing branded heart failure medications. 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. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients.

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. About 6.7 million Americans suffer from heart failure, a progressive, debilitating condition that is becoming more prevalent. Heart failure is the leading cause of hospitalizations for individuals aged 65 and older, triggering approximately 1.3 million hospitalizations a year.

SOLOIST-WHF was a multi-centre, 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 treated with sotagliflozin compared with placebo. SOLOIST-WHF achieved its primary endpoint, with overall tolerability similar to placebo. Results were presented 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 an article titled: “Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure.”

SCORED was a multi-centre, 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 ml 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 events comprised of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure in patients treated with sotagliflozin compared with placebo.

Key secondary endpoints included total number of events of deaths from cardiovascular causes, non-fatal myocardial infarction, and non-fatal stroke. SCORED achieved its primary endpoint, with overall tolerability similar to placebo. Results were presented 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 an article titled: “Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease.” Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives.