FDA Reassesses Lexicon's Previously Rejected Diabetes Drug

The FDA is once again scrutinizing Lexicon Pharmaceuticals' SGLT2 inhibitor, sotagliflozin, in anticipation of an advisory committee meeting scheduled for Thursday. This follows the drug’s rejection in 2019 for the treatment of type 1 diabetes due to safety concerns. Specifically, the FDA had pointed out an unacceptable risk of diabetic ketoacidosis outweighing the drug’s potential benefits. This assessment was detailed in briefing documents released by the agency on Tuesday.

Since the initial rejection, Lexicon Pharmaceuticals has revised its approach. The company is now seeking approval for sotagliflozin for a different patient group - those with chronic kidney disease. The application is supported by post-hoc analyses from three Phase 3 clinical trials. Lexicon hopes that this new indication will meet the FDA's requirements for safety and efficacy.

The dialogue between the FDA and Lexicon has been ongoing since the drug's rejection five years ago. Progress was made in May 2022 when the FDA approved sotagliflozin for use in adults with type 2 diabetes who also suffer from chronic kidney disease and other cardiovascular risk factors. This approval was granted to reduce the risks of cardiovascular death, heart failure-related hospitalizations, and urgent heart failure visits. The drug is marketed under the brand name Inpefa.

However, in December, the FDA communicated to Lexicon that the company needed to provide substantial rationale and statistically meaningful evidence of glycemic control for the proposed chronic kidney disease population. The agency emphasized that the evidence supporting renal benefits of sotagliflozin was still considered exploratory. Consequently, a submission relying on potential renal benefits without clear demonstration could face significant challenges.

The upcoming advisory committee meeting will involve the Endocrinologic and Metabolic Drugs Advisory Committee. The committee will evaluate various aspects of sotagliflozin’s benefits and risks. Key issues to be discussed include the evidence and uncertainty surrounding diabetic ketoacidosis in patients. Additionally, the committee will provide their perspective on whether evidence of benefits observed in type 2 diabetes patients can be applied to those with type 1 diabetes.

Lexicon Pharmaceuticals is hopeful that the revised indication and the supporting clinical trial data will address the FDA’s concerns and ultimately lead to the approval of sotagliflozin for patients with chronic kidney disease. The outcome of the advisory committee’s recommendations will be crucial in determining the future of sotagliflozin in the treatment landscape for diabetes and chronic kidney disease.