The Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) rejecting the New Drug Application (NDA) for Zynquista (sotagliflozin; Sanofi and Lexicon) for the treatment of adults with type 1 diabetes, in combination with insulin.
Sotagliflozin is an investigational dual sodium-glucose co-transporter types 1 and 2 (SGLT1, SGLT2) inhibitor. It works by inhibiting the 2 proteins responsible for glucose regulation: SGLT1 (responsible for glucose absorption in the GI tract) and SGLT2 (responsible for glucose reabsorption by the kidney).
Earlier this year, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted evenly (8 to 8) as to whether the overall benefits of sotagliflozin (Zynquista; Sanofi and Lexicon) outweighed the risks for patients with type 1 diabetes.
The NDA had included data from a phase 3 trial (N=1402) of patients with type 1 diabetes who were receiving insulin therapy. Results showed that a significantly larger proportion of patients in the sotagliflozin group (28.6%) achieved the primary endpoint (glycated hemoglobin level <7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis [DKA]) than the placebo group (15.2%). The committee, however, noted in their briefing documents the pre-specified composite endpoint as a point of concern. The panel also noted a “consistent and clinically meaningful increase” in the risk of DKA associated with sotagliflozin treatment.
The Companies plan to work with the FDA to determine the next steps.