Lexicon Pharmaceuticals Faces Further Delays in Type 1 Diabetes Drug Approval

Lexicon Pharmaceuticals has encountered another setback in its pursuit of regulatory approval for Zynquista, its oral medication designed to improve glycemic control in patients with type 1 diabetes. The U.S. Food and Drug Administration (FDA) has requested additional time to review the company's latest submissions, pushing the timeline for feedback into the fourth quarter of 2025.

Regulatory Hurdles and Safety Concerns

The journey for Zynquista in type 1 diabetes has been fraught with challenges. In December 2024, the FDA issued a complete response letter following an advisory committee meeting where experts voted 11-3 against the drug's approval. The primary concern centered on the unfavorable benefit-risk profile, particularly due to an elevated risk of diabetic ketoacidosis.

In response to the FDA's decision, Lexicon engaged in a type D meeting to discuss the next steps for Zynquista. As part of this process, the company submitted additional data from three ongoing studies earlier this month, aiming to bolster the drug's risk-benefit profile in type 1 diabetes.

Zynquista's Mechanism and Existing Approval

Zynquista, whose active ingredient is sotagliflozin, is a dual inhibitor of SGLT2 and SGLT1 proteins. These proteins play crucial roles in glucose absorption, with SGLT2 acting on the kidneys and SGLT1 affecting the gastrointestinal tract. While the drug faces hurdles in diabetes treatment, it has already gained FDA approval for heart failure under the brand name Inpefa in May 2023.

Lexicon's Pipeline and Recent Developments

Beyond Zynquista, Lexicon is advancing other candidates in its pipeline. The company recently released post-hoc data for pilavapadin, a non-opioid painkiller targeting diabetic peripheral neuropathic pain. Despite a failed Phase IIb PROGRESS trial earlier this year, which showed a lack of separation from placebo in pain outcomes, Lexicon has decided to move forward with Phase III studies based on the new analysis.

As the pharmaceutical industry closely watches Lexicon's regulatory journey with Zynquista, the company continues to navigate the complex landscape of drug development and approval processes.