More Positive Results for Zynquista

Researchers reported positive results for Zynquista (sotagliflozin) today in the Annals of the Internal Medicine, a diabetes drug with a complicated, tortuous past.

Positive results for Zynquista from the SOLOIST-WHF study with respect to heart failure have been reported before. The results reported in the Annals today elaborate on those findings using a metric that that combines “days alive and out of the hospital,” or DAOH, a measure intended to capture a broader, patient-centered effect of a drug, not just its consequences on clinical outcome such as heart failure.

The SOLOIST-WHF trial enrolled just over 1,200 patients with type 2 diabetes who had been hospitalized recently for worsening heart failure. According to the results in the Annals, for every 100 days of follow-up, patients in the Zynquista group were alive and out of the hospital for 2.9 more days than those randomized to receive the placebo.

The large team of researchers led by Michael Szarek, Ph.D., of CPC Clinical Research in Aurora, Colorado, also reported that a similar proportion of patients in the Zynquista and placebo groups were hospitalized at least once (38.5% versus 41.4%) but that fewer patients in the Zynquista group were hospitalized more than once (16.3% versus 22.1%). However, they also said Zynquista's DAOH advantage over placebo was driven mainly by days alive rather than reduced hospitalizations.

The market for sodium glucose co-transporter 2 (SGLT2) inhibitors has become competitive with Farxiga (dapagliflozin), Jardiance (empagliflozin) and Invokana (empagliflozin) jockeying for market share and indications beyond their original purpose as diabetes drugs, April, the FDA approved Farxiga as a treatment for kidney disease and cardiovascular disease for adults with chronic kidney disease.

Zynquista inhibits both SGLT1 and SGLT2, so although it overlaps with the SGLT2 inhibitors, it’s not fully in that class.

Zynquista was developed by Lexicon Pharmaceuticals, a biotech company headquartered in The Woodlands, Texas. In 2019, the FDA rejected Lexicon’s application for Zynquista as a treatment for type 1 diabetes. Then, after some mixed results in later-stage trials of the drug as a treatment for type 2 diabetes, Sanofi, the French drugmaker, pulled out its partnership with Lexicon.

In contrast to the FDA, European Medicines Agency, Europe’s equivalent of the agency, has approved Zynquista as a treatment to be used with insulin in adults with type 1 diabetes who are overweight.

Related:After Setbacks, Good News for Sotagliflozin in Heart Failure, CKD

Today's report in the Annals is the latest piece of positive news about Zynquista. Deepak L. Bhatt, M.D., of Harvard Medical School, reported positive findings from SOLOIST-WHF and another trial, called SCORED, in November 2020 at the American Heart Association Scientific Sessions meeting. The fuller findings from those two studies were published in two separate papers in the Jan. 14, 2021, issue of the New England Journal of Medicine.

Bhatt and his colleagues reported that the SOLOIST-WHF trial showed that among patients with diabetes and recent worsening heart failure, Zynquista lowered the number of deaths from cardiovascular disease and hospitalizations and urgent visits for heart failure.

SCORED was a much larger trial that enrolled more than 10,500 patients with type 2 diabetes and chronic kidney disease. The results, as reported by Bhatt and his colleagues, were similar to those SOLOIST-WHF: a lower risk of death from cardiovascular disease and fewer hospitalizations and urgent care visits related to heart failure among patients randomized to take Zynquista than among those randomized to take the placebo. However, adverse events, including diarrhea, genital mycotic infections, and diabetic ketoacidosis were more common in the Zynquista group.

Sanofi and Lexicon funded both trials and both were cut short after Sanofi left its partnership with Lexicon and pulled funding for research.