FDA Advisory Committee Rejects Zynquista for Type 1 Diabetes and Chronic Kidney Disease
Key Insights
The FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted against approving Zynquista (sotagliflozin) for adults with type 1 diabetes (search) and chronic kidney disease (search).
The committee cited concerns that the benefits of Zynquista do not outweigh the risks in the studied population with specific eGFR and uACR levels.
Lexicon Pharmaceuticals expressed disappointment but noted support for sotagliflozin in specific subpopulations and will continue to work with the FDA.
Lexicon Pharmaceuticals' Zynquista (sotagliflozin), an oral SGLT1 (search)/SGLT2 (search) inhibitor, faced a setback as the FDA's Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) voted against its approval for glycemic control in adults with type 1 diabetes (search) (T1D) and chronic kidney disease (search) (CKD). The committee's decision, with a vote of 11 to 3, indicated that the benefits of Zynquista do not outweigh the risks in this patient population.
The primary concern raised during the meeting focused on patients with an estimated glomerular filtration rate (eGFR) >45 to <60 mL/min/1.73 m2 or eGFR >60 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (uACR) > 30mg/g. Some committee members expressed support for sotagliflozin in alternative subpopulations of people with T1D and CKD, where they believed the benefits potentially outweigh the risks.
Company Response and Future Steps
Dr. Mike Exton, CEO of Lexicon Pharmaceuticals, expressed disappointment with the outcome but acknowledged the support for sotagliflozin within the diabetes community. He emphasized the urgent need for an FDA-approved treatment and clear education on managing risk for this patient population. Lexicon plans to collaborate with the FDA as it finalizes its review of the New Drug Application (NDA) and remains hopeful about making Zynquista available to appropriate patients if approved.
Clinical Context and Unmet Needs
According to Dr. Steve Edelman, a professor at UCSD, only 20% of people with T1D achieve adequate glycemic control with insulin alone. Zynquista, if approved, would represent a significant advancement as the first oral medication for this population, potentially improving renal and cardiovascular outcomes, particularly in those with CKD.
About Sotagliflozin
Sotagliflozin, discovered through Lexicon's genomics program, is an oral inhibitor targeting both SGLT2 (search) and SGLT1 (search) proteins. SGLT2 is responsible for glucose and sodium reabsorption in the kidney, while SGLT1 manages glucose and sodium absorption in the gastrointestinal tract. Clinical studies involving approximately 20,000 patients have explored sotagliflozin's effects across various populations, including those with heart failure, diabetes, and chronic kidney disease (search).
The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of December 20, 2024, for its final decision on the approval of Zynquista.