Sotagliflozin in Patients with Type 1 Diabetes and CKD to be Discussed at October FDA AdComm Meeting

The FDA has set a date of October 31, 2024, for a meeting of the Endocrinologic and Metabolic Drugs Advisory Committee to discuss sotagliflozin (Zynquista; Lexicon Pharmaceuticals) as an adjunct to insulin therapy to help control glycemic levels in adults with type 1 diabetes (T1D) and chronic kidney disease (CKD).¹

The agency’s Prescription Drug User Fee Act (PDUFA) goal, set in July this year, is December 20, 2024.²

Sotagliflozin is an inhibitor of sodium glucose cotransporters 2 and 1, which are responsible for glucose regulation in the kidney and gastrointestinal tract, respectively. Lexicon officials have not indicated what regulatory officials would like the advisory committee to discuss regarding the sotagliflozin new drug application (NDA).

“Lexicon looks forward to the opportunity to share the breadth of evidence that has been generated to support the favorable benefit/risk profile of sotagliflozin for glycemic control in people with type 1 diabetes and CKD,” Mike Exton, PhD, chief executive officer and director, Lexicon Pharmaceuticals, said in a statement.¹

Lexicon had resubmitted the NDA for sotagliflozin in the diabetes indication in June 2024 following a 2019 complete response letter from the FDA after an initial filing.

Sotagliflozin was approved by the FDA as Inpefa in May 2023 as a once-daily oral tablet that reduces the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure or type 2 diabetes, CKD, and other cardiovascular risk factors.³

Data were presented in March 2024 from the phase 3 inTandem3 clinical trial.⁴ The trial found that treatment with sotagliflozin resulted in improved glycemic control in patients with type 1 diabetes and chronic kidney disease (CKD). Sotagliflozin successfully reduced HbA1c, body weight, and systolic blood pressure with a safety profile similar to the total study cohort.

Using data from the 24-week trial, the effects of sotagliflozin 400 mg daily added to insulin therapy on HbA1c, body weight, systolic blood pressure, eGFR, total insulin dose, adjudicated severe hypoglycemia and DKA were evaluated in a subgroup of 228 patients with type 1 diabetes and CKD (eGFR <60 mL/min/1.73 m² and/or UACR ≥30 mg/g).⁴

Compared with placebo, treatment with sotagliflozin led to similar reductions in HbA1c, body weight and systolic blood pressure in the CKD and total cohorts. Similar risks of severe hypoglycemia were recorded in both cohorts.⁴

“Lexicon has continued confidence in the favorable benefit/risk profile of sotagliflozin for adults with type 1 diabetes and CKD. With a PDUFA date now in hand, we can begin the next phase of launch preparation for Zynquista,” Mike Exton, PhD, chief executive officer and director, Lexicon Pharmaceuticals, said in a statement.¹

References
1. Lexicon Pharmaceuticals Announces FDA Advisory Committee Meeting for Zynquista. News release. Lexicon Pharmaceuticals. August 21, 2024. Accessed October 10, 2024. https://www.lexpharma.com/media-center/news/2024-08-21-lexicon-pharmaceuticals-announces-fda-advisory-committee-meeting-for-zynquista
2. Lexicon Pharmaceuticals Receives December 20, 2024 PDUFA Goal Date for Sotagliflozin Type 1 Diabetes NDA Resubmission. News release. Lexicon Pharmaceuticals. July 16, 2024. Accessed Oct ??? 2024 https://www.lexpharma.com/media-center/news/2024-07-16-lexicon-pharmaceuticals-receives-december-20-2024-pdufa-goal-date-for-sotagliflozin-type-1-diabetes-nda-resubmission
3. Halsey G. FDA approves SGLT2/1 inhibitor sotagliflozin, grants broad heart failure indication. Patient Care. May 30, 2024. https://www.patientcareonline.com/view/fda-approves-sglt-2-1-inhibitor-sotagliflozin-grants-broad-heart-failure-indication
4. New Post Hoc Analysis of inTandem3 Study Demonstrates Improvements in Glycemic Control With Sotagliflozin Treatment in Patients With Type 1 Diabetes and Chronic Kidney Disease. News release. Lexicon Pharmaceuticals. March 12, 2024. Accessed October ?? 2024. https://www.lexpharma.com/media-center/news/2024-03-12-new-post-hoc-analysis-of-intandem3-study-demonstrates-improvements-in-glycemic-control-with-sotagliflozin-treatment-in-patients-with-type-1-diabetes-and-chronic-kidney-disease