An FDA Endocrinologic and Metabolic Drugs Advisory Committee has voted against Lexicon Pharmaceuticals' sotagliflozin as an adjunct to insulin for managing blood glucose in adults with type 1 diabetes and chronic kidney disease. The committee's decision, delivered on Thursday, was based on concerns that the drug's benefits do not outweigh its risks, and that Lexicon has not provided sufficient clinical data to support its approval.
The vote was 11-3 against the approval of sotagliflozin. Panelists, including Cecilia Low Wang, professor of medicine at the University of Colorado, expressed reservations about the data presented. Wang stated, "I actually didn’t see any data that demonstrated that the benefits outweighed the risk for this indication... I really feel like we need a prospective trial."
Concerns Over Benefit-Risk Profile
Key concerns raised by the advisory committee centered on the benefit-risk profile of sotagliflozin, particularly in patients with varying degrees of kidney disease. Connie Newman, adjunct professor at the New York University School of Medicine, noted, "I felt that there was an uncertainty about the benefit-risk... The group with GFR from 60 and 90 might be a population that will have a greater benefit than risk … and I would prefer to see more data in that population before I can make a decision about benefit-risk."
The committee members indicated that the drug may have a more favorable risk-benefit ratio in patients with eGFR values between 60 and 90, indicative of relatively mild kidney damage. They suggested that additional data focusing on this subgroup would be necessary to make a more informed decision.
Lexicon's Response and Future Outlook
Lexicon Pharmaceuticals CEO Mike Exton expressed disappointment with the advisory committee's decision. "We were encouraged by the rich discussion and outpouring of support across the diabetes community," Exton stated. He also emphasized the "urgent" need for an FDA-approved treatment and clear education on managing risk in this patient population.
Sotagliflozin functions as a dual inhibitor of SGLT2 and SGLT1 proteins, which are involved in glucose absorption in the kidneys and gastrointestinal tract. Lexicon supported its application with data from three Phase III trials, which, according to Exton's briefing document, demonstrated "consistent improvements in glycemic control and body weight."
Regulatory History and Upcoming Decision
This is not the first regulatory hurdle for sotagliflozin. In 2019, the FDA issued a Complete Response Letter for the drug. Prior to that rejection, an advisory committee vote was split 50-50 on the drug's approval.
The FDA is scheduled to make its final decision on sotagliflozin by December 20. While the agency is not required to follow the advisory committee's recommendation, it often does.
