FDA Panel Rejects Lexicon's Zynquista for Type 1 Diabetes
核心洞察
An FDA advisory committee voted against approving Lexicon's Zynquista (sotagliflozin) as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes (搜索) (T1D) and chronic kidney disease (搜索) (CKD).
The committee cited that the benefits of Zynquista do not outweigh the risks for the proposed patient population.
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of December 20 for the final decision on Zynquista.
Lexicon Pharmaceuticals' hopes for Zynquista (sotagliflozin) in treating type 1 diabetes (搜索) (T1D) have been dealt a blow as an FDA advisory committee voted against its approval. The Endocrinologic and Metabolic Drugs Advisory Committee reviewed the New Drug Application (NDA) for sotagliflozin, an oral SGLT1/SGLT2 (搜索) inhibitor intended as an adjunct to insulin therapy for glycemic control in adults with T1D and chronic kidney disease (搜索) (CKD). The committee voted 11 to 3 that the benefits of Zynquista do not outweigh the risks for patients with an estimated glomerular filtration rate (eGFR) >45 to <60 mL/min/1.73 m2 or eGFR >60 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (uACR) > 30mg/g.
Committee Concerns and Alternative Sub-populations
During the discussion, some committee members expressed support for sotagliflozin in specific sub-populations of T1D and CKD patients, suggesting that the benefits might outweigh the risks in these groups. The FDA is scheduled to make a final decision by December 20, the Prescription Drug User Fee Act (PDUFA) target action date.
Sotagliflozin's Regulatory History
Sotagliflozin received FDA approval in May 2023, branded as Inpefa, to reduce the risk of cardiovascular death, hospitalization for heart failure (搜索), and urgent heart failure visits in adults with heart failure or type 2 diabetes mellitus (搜索), chronic kidney disease (搜索), and other cardiovascular risk factors. However, in 2019, the FDA issued a complete response letter (CRL) for sotagliflozin's NDA for type 1 diabetes (搜索). Despite the FDA's initial rejection, the European Medicines Agency approved the drug in April 2019 for T1D patients who could not achieve adequate glycemic control despite optimal insulin therapy.
Lexicon's Efforts and Partnerships
In 2021, Lexicon requested a public Notice of Opportunity for Hearing (NOOH) from the FDA regarding the denial of approval. Lexicon and the FDA agreed to hold the NOOH proceedings in abeyance to discuss a path forward for resubmission and potential approval of the NDA. Lexicon resubmitted its NDA for sotagliflozin in June, anticipating a six-month review and a potential launch in early 2025. Previously, Sanofi SA (搜索) terminated its sotagliflozin-related agreement with Lexicon in 2019, paying Lexicon $260 million. Recently, Viatris Inc. secured an exclusive license from Lexicon to commercialize sotagliflozin in all indications outside the U.S. and Europe, while Lexicon retains sole commercialization rights in the U.S. and Europe.