The Food and Drug Administration (FDA)’s Endocrinologic and Metabolic Drugs Advisory Committee were evenly split (8 to 8) as to whether the overall benefits of sotagliflozin (Zynquista; Sanofi and Lexicon) outweigh the risks for patients with type 1 diabetes.
Sotagliflozin is an investigational dual sodium-glucose co-transporter types 1 and 2 (SGLT1, SGLT2) inhibitor, intended for use with insulin to improve glycemic control in adults with type 1 diabetes. 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).
According to data from the inTandem clinical trial program, which included three Phase 3 studies in nearly 3000 patients, both doses of sotagliflozin in combination with insulin therapy and glucose management resulted in statistically significant and clinically meaningful reductions in HbA1c. However, in the briefing documents, the FDA flagged the pre-specified composite endpoint of HBA1c <7% with no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA) as a point of concern. “This endpoint attempts to incorporate benefit and risk into a single composite, but we have concerns about the clinical significance of the chosen composite. For one, the composite uses a responder rate for glycemic efficacy (achieving or not achieving HbA1c <7%), and for example, puts equal weight on a lowering from 7.5% to 6.9% as on a lowering from 9.5% to 6.9%.”
The panel also noted a “consistent and clinically meaningful increase” in the risk of DKA associated with sotagliflozin treatment, adding that “while all patients with type 1 diabetes may to some degree be at risk for DKA, sotagliflozin therapy clearly increases that risk, and the risk may be unpredictable.” Responding to the issue of DKA, Pablo Lapuerta, MD, Executive Vice President and Chief Medical Officer of Lexicon stated in a press release that the issue could potentially be addressed with proper education and monitoring.
The FDA takes the advice of the panel into consideration when making decisions, however it is not bound by their recommendations. If approved, sotagliflozin would be the first oral antidiabetic agent used in combination with insulin to improve glycemic control in patients with type 1 diabetes.
“We believe in the overall benefit-risk profile of sotagliflozin for adults with type 1 diabetes who lack adequate glycemic control using insulin alone,” said Rachele Berria, MD, PhD, Global Vice President and Head of Diabetes Medical Affairs, Sanofi. “We will continue to work with the FDA through its review process to hopefully bring to patients a new treatment that can help people living with type 1 diabetes control their blood sugar and address some of the challenges of insulin-only therapy.”
For more information visit FDA.gov.