Lexicon Pharmaceuticals' Zynquista (sotagliflozin), an oral SGLT1/SGLT2 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 (T1D) and chronic kidney disease (CKD). The committee's decision, reached on October 31, 2024, saw a vote of 11 to 3 against the drug's benefits outweighing its risks in the specified patient population.
The primary concern raised during the EMDAC 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. However, some committee members indicated potential support for sotagliflozin in alternative subpopulations of T1D and CKD patients where they perceived a more favorable benefit-risk profile.
Company Response and Expert Opinions
Dr. Mike Exton, CEO of Lexicon Pharmaceuticals, expressed disappointment with the outcome but acknowledged the supportive discussion and the recognized need for new treatments within the diabetes community. He stated, "It’s clear from today’s discussion that an FDA-approved treatment and clear education on managing risk is urgently needed, and we believe our data supports this need." Lexicon intends to collaborate with the FDA as it finalizes its review.
Dr. Steve Edelman, a professor of medicine at UCSD and founder of Taking Control Of Your Diabetes (TCOYD), emphasized the limitations of insulin alone in managing T1D. He noted that only 20% of T1D patients achieve adequate glycemic control with insulin monotherapy. "Zynquista, if approved, would be the first oral medication for people with T1D, with potential to impact renal and cardiovascular outcomes, especially in those with CKD who face even greater disease progression risks," said Edelman.
Sotagliflozin Mechanism and Clinical Development
Sotagliflozin is a dual inhibitor of sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption in the kidney, while SGLT1 facilitates glucose and sodium absorption in the gastrointestinal tract. Lexicon's drug has been studied in approximately 20,000 patients across various clinical trials encompassing heart failure, diabetes, and chronic kidney disease.
Regulatory Timeline
The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of December 20, 2024, for its final decision on the Zynquista NDA. While the advisory committee's vote is non-binding, the FDA typically considers its recommendations during the review process.
