Lexicon Pharmaceuticals faces uncertainty as an FDA advisory committee voted against recommending sotagliflozin for treating hyperglycemia in adults with type 1 diabetes (T1D) and mild-to-moderate chronic kidney disease (CKD). The Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) voted 11 to 3 that the benefits of the dual sodium glucose cotransporter-1 and -2 inhibitor (SGLT1/SGLT2i) do not outweigh the risks when added to insulin therapy.
The FDA's final decision, which will factor in the EMDAC discussions, is expected by December 20, 2024, the Prescription Drug User Fee Act (PDUFA) date. While the advisory committee's recommendations are non-binding, they carry significant weight.
Concerns and Potential Benefits
During the discussion, some committee members suggested that sotagliflozin might be beneficial in specific subpopulations of T1D and CKD patients where the benefits could potentially outweigh the risks. Steve Edelman, MD, professor of medicine at the University of California, San Diego, noted that only 20% of people with T1D achieve adequate glycemic control with insulin alone. He stated sotagliflozin, if approved, could be the first oral medication for people with T1D, potentially impacting renal and cardiovascular outcomes, especially in those with CKD.
History of the NDA
The FDA previously issued a complete response letter to Lexicon's original NDA in 2019, citing concerns about the elevated risk for diabetic ketoacidosis (DKA) observed during the phase 3 inTandem clinical trial program. The current application includes data from post hoc analyses of the CKD population within the original phase 3 trials. FDA briefing documents reiterated concerns about DKA and questioned the durability of treatment response in adults with T1D and an estimated glomerular filtration rate (eGFR) of 45 to <60 mL/min/1.73 m2 or an eGFR ≥60 mL/min/1.73 m2 and a urine albumin-creatinine ratio of ≥30 mg/g.
Company Response
Lexicon maintains its belief that the risk of DKA can be managed and is balanced by the unmet needs in the T1D population. Mike Exton, PhD, CEO of Lexicon, expressed disappointment with the advisory committee vote but noted the support from the diabetes community for making sotagliflozin available to appropriate patients with T1D and CKD. He emphasized the urgent need for an FDA-approved treatment and clear education on managing risk.
Sotagliflozin's Existing Approval
The NDA under consideration includes data on sotagliflozin's use in adults with type 2 diabetes (T2D) and moderate-to-severe CKD. The FDA approved sotagliflozin (marketed as Inpefa) last year to reduce the risk of cardiovascular death, emergency visits, or hospital admission for heart failure in adults with the condition, and in adults with T2D, CKD, and other CV risk factors.
