Lexicon to face FDA panel for Zynquista approval in diabetes and CKD

Lexicon Pharmaceuticals is once again seeking approval from the US Food and Drug Administration (FDA) for its drug Zynquista (sotagliflozin) as an adjunct to insulin in adults with type 1 diabetes (T1D) and chronic kidney disease (CKD). The FDA has scheduled an advisory committee (AdComm) meeting to assess the drug’s efficacy and safety, set to take place on October 31, 2024.

The FDA’s Endocrinologic and Metabolic Drugs AdComm will focus on the benefit-risk profile of Zynquista, particularly as it pertains to glycemic control in T1D patients. This review process is part of the standard procedure where an AdComm evaluates the safety and efficacy data of a therapy and makes recommendations to the FDA. However, it's important to note that these recommendations are not binding, and the FDA will make the final decision.

Lexicon has faced challenges in getting Zynquista approved in the past. In 2019, the FDA did not approve the drug due to safety concerns, following a split decision from the AdComm, which had an 8-8 vote. The primary concern was the risk of diabetic ketoacidosis, a severe and potentially life-threatening complication if not treated promptly.

Despite these setbacks in the US, Lexicon did achieve approval for Zynquista from the European Medicine Agency (EMA) in 2019 for use as an adjunct treatment to insulin in T1D and CKD. However, the company could not maintain its licensing agreement with Sanofi for the drug.

In light of these challenges, Lexicon remains committed to advancing Zynquista's development and securing its approval. To manage costs, the company recently implemented cash-saving measures, including a 50% reduction in its current field force, which is expected to take effect in the third quarter of this year.

Zynquista is an oral inhibitor that targets the sodium-dependent glucose co-transporter types 1 and 2 (SGLT1 and SGLT2), which are involved in glucose uptake and reabsorption. The drug has already received FDA approval to reduce the risk of cardiovascular death and heart failure. It is also approved for use in patients with type 2 diabetes, CKD, and other cardiovascular risk factors, marketed under the name Inpefa for these indications.

Beyond its current applications, Lexicon is exploring additional uses for sotagliflozin. The company is conducting a Phase III trial to evaluate the drug’s effectiveness in treating hypertrophic cardiomyopathy. This trial, which is placebo-controlled, aims to assess the drug in patients experiencing symptomatic hypertrophic cardiomyopathy.

In summary, Lexicon Pharmaceuticals is making another attempt to secure FDA approval for Zynquista as an adjunct treatment for T1D and CKD. The upcoming AdComm meeting will play a crucial role in evaluating the drug's safety and efficacy, although the final decision will rest with the FDA. Despite previous setbacks, the company is optimistic and continues to explore new therapeutic applications for sotagliflozin.