An advisory committee last year found that Zynquista’s benefit-risk profile in type 1 diabetes was unfavorable due to cases of diabetic ketoacidosis.
Lexicon Pharmaceuticals will wait a few months more on moving Zynquista forward in type 1 diabetes, after the FDA requested more time to review the biotech’s additional submissions for the drug.
Following a complete response letter in December 2024, the agency granted Lexicon a type D meeting to discuss the next regulatory steps for Zynquista. In connection with this meeting, the biotech earlier this month submitted additional data from three ongoing studies to support the risk-benefit profile of Zynquista in this indication.
The FDA was originally supposed to give its feedback from the type D meeting by the end of this month but has now pushed that timeline back into the fourth quarter, according to Lexicon’s news release on Monday.
Designed to be taken alongside insulin, Zynquista is an oral drug that Lexicon is proposing for improving glycemic control in patients with type 1 diabetes. Its active ingredient, sotagliflozin, is a dual inhibitor of the SGLT2 and SGLT1 proteins, both of which play key roles in glucose absorption in different organs: The former acts on the kidneys while the latter exerts its effects on the gastrointestinal tract. Sotagliflozin won the FDA’s blessing in May 2023 for heart failure, for which it is marketed as Inpefa.
Its path in diabetes, however, has yet to bear fruit. In October 2024, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee came together to discuss Lexicon’s application—and handed the biotech a decisive defeat. Voting 11–3, the panel of external experts found that Zynquista’s benefits in type 1 diabetes do not outweigh its risks, according to reporting from Fierce Pharma at the time, pointing to an elevated risk of diabetic ketoacidosis.
The FDA followed the recommendations of its advisors months later, handing Lexicon a complete response letter. The biotech had anticipated the rejection and a few days prior had discontinued launch preparations for Zynquista.
Monday’s FDA delay comes after Lexicon last week released post-hoc data for its non-opioid painkiller pilavapadin, supporting its decision to advance the asset into Phase III despite a failed mid-stage trial. The Phase IIb PROGRESS trial focused on patients with diabetic peripheral neuropathic pain and in March this year failed to show a “lack of separation” versus placebo in terms of pain outcomes.
