Lexicon Pharmaceuticals received approval for sotagliflozin to treat a broad range of left ventricular ejection fraction, for patients with and without diabetes.
The FDA late Friday approved sotagliflozin, the first dual sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor, for the treatment of the full range of heart failure (HF), with both preserved and reduced ejection fraction. The approval was granted to Lexicon Pharmaceuticals, which succeeded in gaining a broad HF label that includes patients with and without diabetes.
The therapy will be marketed as Inpefa, according to a statement from Lexicon.
Although the class of SGLT2 inhibitors is well known in the areas of HF, chronic kidney disease, and type 2 diabetes (T2D), a therapy coming to market that also blocks SGLT1 is new.
SGLT2 inhibitors were developed to treat T2D by targeting a protein in the kidney that normally allows the body to retain blood glucose. SGLT2 prevents the reabsorption of more than 90% of the body’s glucose filtered through kidney tissues.
After FDA cardiovascular safety trials for T2D showed unexpected benefits in HF and preserving renal function, companies raced to launch studies to show new uses for the drugs (empagliflozin, dapagliflozin, and canagliflozin). Potential SGLT1 inhibitors go another step and block the remaining 10% of glucose, mostly in the epithelial cells of the small intestine.
Originally, Lexicon Pharmaceuticals sought an indication for sotaglifozin in type 1 diabetes (T1D), in conjunction with its then-marketing partner, Sanofi. But in 2019, the FDA rejected the drug for that use, raising safety concerns about the development of diabetic ketoacidosis; Lexicon appealed the agency on its decision.
However, this week’s approval was based on phase 3 results of the SOLOIST-WHF trial, which randomized 1222 patients with T2D who had been recently hospitalized for worsening HF.
The first dose of the drug or placebo (608 patients were in the sotagliflozin group and 614 were in the placebo group) was administered just before or just after hospital discharge, and patients were followed for a median of 9.0 months.
In the sotagliflozin group, 245 end point events occurred, and in the placebo group, 355 end points. Results showed a 33% reduced cardiovascular event rate for patients taking sotagliflozin compared with those taking placebo, as well as fewer deaths.
The rate of primary end point events was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; HR, 0.67; 95% CI, 0.52-0.85; P < .001).
In addition, the cardiovascular death rate was 10.6 in the sotagliflozin group and 12.5 in the placebo group (HR, 0.84; 95% CI, 0.58-1.22) and the rate of death from any cause, 13.5 in the sotagliflozin group and 16.3 in the placebo group (HR, 0.82; 95% CI, 0.59-1.14).
Some adverse events were more common with sotagliflozin than with placebo (diarrhea and severe hypoglycemia), but the percentage of patients with hypotension and acute kidney injury was similar for both groups.
"The approval of Inpefa along with the breadth of the label is a major milestone in Lexicon's path to fulfilling the mission of pioneering medicines that transform patients' lives," Lionel Coats, Lexicon's CEO, said in the statement. Sotagliflozin should reach the market by the end of June, he said.
In the European Union, sotagliflozin has been approved as an add-on therapy for T1D in adults under the name Zynquista but it is not currently marketed there.