- Expert advisers to the Food and Drug Administration were split down the middle over whether Lexicon Pharmaceuticals and Sanofi's Zynquista, an oral dual SGLT1 and SGLT2 inhibitor, should be recommended for approval as an add-on to insulin for improving blood sugar control in Type 1 diabetes.
- While Zynquista did reduce body weight and hypoglycemia, and improve glycemic control by lowering HbA1C, the 8-8 vote likely reflects concerns raised in an FDA staff briefing document over increases in diabetic ketoacidosis (DKA) seen across a trio of Phase 3 clinical trials.
- With a user fee action date of March 22, 2019, the approval decision now goes to the FDA itself, which takes into consideration — but does not have to follow — the advice of its advisory panels.
The split surprised investors in the small biotech, which focuses on diabetes and neuropathic pain, pushing down shares in Lexicon 35% before the market opened Friday. Shares were trading down about 20% by late morning, while shares in the larger Sanofi were relatively unmoved.
The companies now await an FDA decision on Zynquista (sotagliflozin), which if approved would be the first oral antidiabetic drug in the U.S. for use with insulin for Type 1 diabetes.
The inconclusive vote by Endocrinologic and Metabolic Drugs Advisory Committee came after agency staffers raised several flags in their briefing documents to the panel.
Some of the concerns were related to the risk of DKA, which FDA called the "most notable and concerning adverse event" linked to the drug. Briefing documents said there's about an eight-fold boost in DKA risk compared with placebo.
All three Phase 3 trials showed increases in DKA compared with placebo. DKA can be life-threatening, causing symptoms like vomiting, abdominal pain and loss of consciousness.
Lexicon maintains that Zynquista improves glycemic control without increasing hypoglycemia to a degree that could not be achieved with insulin alone, and that the drug's benefit balances the risk.
"Diabetic ketoacidosis is an inherent risk of Type 1 diabetes and an increase was seen with sotagliflozin compared to insulin alone," said Pablo Lapuerta, the company's chief medical officer, in a statement. "We believe this can potentially be addressed with proper education and monitoring."
The proposed indication to improve glycemic control holds big market potential: about 1.3 million people in the U.S. have Type 1 diabetes.
Zynquista is also pending approval in Europe, with a launch predicted for the second half of 2019.