While an FDA advisory committee saw signals of efficacy for Lexicon Pharmaceuticals’ sotagliflozin, the panel of external experts found that the company did not provide enough data to support its drug application.
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee on Thursday voted against Lexicon Pharmaceuticals’ investigational type 1 diabetes therapy sotagliflozin.
In an 11–3 vote, the panel of external experts found that sotagliflozin’s benefits do not outweigh its risks and that Lexicon has not provided enough clinical data to back the drug candidate. Lexicon is proposing sotagliflozin as an adjunct to insulin to help control blood glucose levels in patients with type 1 diabetes and chronic kidney disease.
CEO Mike Exton in a statement said that Lexicon is “disappointed” by the outcome of the advisory committee vote, adding “we were encouraged by the rich discussion and outpouring of support across the diabetes community.” Thursday’s advisory committee meeting demonstrated the “urgent” need for an “FDA-approved treatment and clear education on managing risk,” Exton said.
Sotagliflozin is a dual inhibitor of the SGLT2 and SGLT1 proteins, both of which function in the absorption of glucose in the kidney and gastrointestinal tract. Lexicon backed sotagliflozin’s application with three pivotal Phase III studies, which showed “consistent improvements in glycemic control and body weight,” according to Exton’s briefing document, published ahead of the adcomm meeting.
Panelists on Thursday, however, were not convinced. “I actually didn’t see any data that demonstrated that the benefits outweighed the risk for this indication,” Cecilia Low Wang, professor of medicine at the University of Colorado, said during the meeting. “The numbers were incredibly small. I really feel like we need a prospective trial.”
“I very much want an adjunctive drug for my patients with type 1 [diabetes]. I just don’t feel that it would fulfill my obligation to vote to approve something with so little supportive data. I feel like it does my patients a disservice,” Low Wang said.
The external experts wanted to see more data in patients with eGFR values from 60 to less than 90, indicating relatively mild kidney damage or earlier-stage disease, for whom sotagliflozin appears to be more beneficial.
“I felt that there was an uncertainty about the benefit-risk,” Connie Newman, adjunct professor in the Department of Medicine at the New York University School of Medicine, said during the meeting. “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.”
Thursday’s adcomm loss comes after a previous regulatory stumble in 2019, when the FDA hit the drug with a Complete Response Letter. Months before the rejection, the Endocrinologic and Metabolic Drugs Advisory Committee was split 50-50 on sotagliflozin, with many panelists expressing skepticism regarding the risk-benefit profile of the drug.
The FDA is currently reviewing Lexicon’s application for sotagliflozin and is set to release its decision on Dec. 20. The adcomm’s vote is non-binding and the FDA is not required to follow its recommendations, though the regulator often does.
