FDA Approves SGLT-2/1 Inhibitor Sotagliflozin, Grants Broad Heart Failure Indication

The US Food and Drug Administration on May 26, 2023, approved sotagliflozin (Inpefa) for the treatment of heart failure across the full range of left ventricular ejection fraction.

Sotagliflozin, a novel combined inhibitor of the sodium glucose cotransporter (SGLT) -1 and SGLT-2 proteins, is a once-daily oral tablet approved to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes (T2D), chronic kidney disease (CKD), and other cardiovascular (CV) risk factors, according to a statement from biopharmaceutical company Lexicon Pharmaceuticals.

In the key registration trial, sotagliflozin reduced the total risk of CV death and worsening heart failure events by 33% compared to placebo, Lexicon stated.

“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,” said Lonnel Coats, Lexicon chief executive officer. “We expect this important innovation to be commercially available in the U.S. market by the end of June 2023.”

Pivotal phase 3 trials

Approval of sotagliflozin, currently the first and only FDA-approved combined SGLT-1/2 inhibitor, follows authorization of labels for SGLT-2 inhibitors dapagliflozin and empagliflozin, both also indicated for heart failure across the spectrum of ejection fraction. The FDA’s decision was based on data it reviewed from the phase 3 SOLOIST-WHF and SCORED trials.

SOLOIST-WHF was a phase 3, double-blind, randomized, placebo-controlled trial with a cohort of 1222 patients with T2D who had been recently hospitalized for worsening heart failure. The trial’s primary endpoint was a composite of total CV deaths and worsening heart failure events.

During a median follow-up of 9 months the rate of primary endpoint events was significantly reduced among sotagliflozin-treated participants vs those treated with placebo (hazard ratio [HR], 0.67; 95% CI, 0.52-0.85; P<.001). Study investigators reported that sotagliflozin was associated with reductions in risk of CV mortality (HR, 0.84; 95% CI, 0.58-1.22) as well as all-cause mortality compared with placebo therapy. Treatment effec for the the primary composite endpoint achieved significance by 28 days of follow-up, according to a posthoc analysis of SOLOIST-WHF.

The phase 3, double-blind, randomized placebo controlled SCORED trial enrolled a patient population with T2D, CKD, and risks for CV disease. The trial’s primary endpoint comprised a composite of CV death or worsening heart failure events.

The final cohort of 10 584 was followed for a median of 16 months. The SCORED investigators reported that the rate of primary endpoint events was significantly reduced among those receiving sotagliflozin vs the group receiving placebo (HR, 0.74; 95% CI, 0.63-0.88; P=.0004). Posthoc analysis findings for this trial revealed a treatment effect for the endpoint of CV death and worsening heart failure achieved significance by 95 days of follow-up.

Overall tolerability of sotagliflozin in both trials, according to Lexicon, was similar to placebo. Results of both studies were originally presented at the American Heart Association Scientific Sessions 2020 and published simultaneously in the New England Journal of Medicine.

“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, MD, PhD, Lexicon 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.”