FDA CRL - Lexicon Pharmaceuticals Inc

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for Lexicon Pharmaceuticals, Inc.'s New Drug Application (NDA 210934) for sotagliflozin tablets. The FDA determined that the application cannot be approved in its current form due to an unfavorable benefit-risk assessment.

The primary issue identified was an "unacceptably high" risk of diabetic ketoacidosis (DKA) observed in sotagliflozin-treated patients across phase 3 clinical trials in adults with type 1 diabetes mellitus (T1D). The FDA concluded that the modest benefits in glycemic control and other non-glycemic factors did not outweigh this significant DKA risk, particularly in the proposed population of T1D patients with chronic kidney disease (CKD). Efficacy in T1D patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73m2 was also not sufficiently established.

To address these deficiencies, Lexicon Pharmaceuticals must provide prospective clinical data demonstrating that patient selection criteria and/or risk mitigation strategies can adequately reduce the incidence or severity of DKA events. This may involve a pragmatic open-label randomized clinical safety trial with a standard-of-care comparator, or a single-arm study with an external control. Additional glycemic control data is also required for T1D patients with eGFR <60 ml/min/1.73m2. The FDA encourages an End-of-Review meeting to discuss the path forward.