- The Food and Drug Administration hit Sanofi and Lexicon Pharmaceutical's experimental Type 1 diabetes treatment with a Complete Response Letter, the companies said Friday.
- While the French drugmaker and its smaller Texas-based partner did not give any reasons for the rejection letter, a prior FDA advisory committee meeting had laid out concerns surrounding the safety of Zynquista. "Sanofi and Lexicon will work closely with the FDA to determine the appropriate next steps," the companies stated.
- That expert panel was evenly split on recommending the drug, setting up the regulatory decision for the agency. One of the main concerns was around data from late-stage clinical studies showing increases in diabetic ketoacidosis, according to briefing documents prepared by agency staff for that January meeting.
If approved, Zynquista (sotagliflozin) would have become the first oral Type 1 diabetes drug used with insulin in the U.S. Instead, for reasons undisclosed by the companies, the FDA rejected its application.
Aaron Kowalski, chief mission officer of the nonprofit Type 1 diabetes research group JDRF, said in a statement the organization is disappointed with the decision, noting the lack of different types of treatment for Type 1 diabetes.
"It is critical that we add new therapy options for people with T1D in order to address the unmet needs of our community," Kowalski said.
Zynquista is an experimental dual SGLT1 and SGLT2 inhibitor, designed for Type 1 diabetic adults to be used in combination with insulin. Sanofi and Lexicon filed applications for the drug in the U.S. and Europe in March 2018.
While the FDA is not on board — at least yet — the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended Zynquista's approval earlier this year. That leaves a final decision on marketing authorization to the European Commission.
FDA staff had expressed concern with the drug's adverse event profile. According to the January meeting's briefing documents, Zynquista carried an eight-fold increase to risk of diabetic ketoacidosis, calling it the "most notable and concerning adverse event."
Diabetic ketoacidosis can be a life-threatening complication from diabetes, where the body produces too much blood acids.
Other SGLT2 inhibitors from AstraZeneca, Eli Lilly and Johnson & Johnson are already established on the market for Type 2 diabetes. Expanding into Type 1 could represent another opportunity.
AstraZeneca's Farxiga (dapagliflozin), for instance, gained CHMP approval for Type 1 earlier this year. U.S. regulators are reviewing that drug as well in Type 1, which would expand upon a 2014 OK for Type 2.
Zynquista was originally developed by Lexicon, with Sanofi teaming up through an R&D deal in 2015. The French pharma paid $300 million upfront in that agreement and lined up to $1.4 billion in milestone payments based on development, regulatory and sales achievements.
Lexicon's stock dropped more than 20% Friday, while Sanofi was down about 2.5%.
Correction: This article has been updated to reflect the correct spelling of sotagliflozin.