Recently, the FDA announced that it has accepted Sanofi’s New Drug Application (NDA) for Zynquista (sotagliflozin). If approved, oral Zynquista will be used in combination with insulin to improve glycemic control in adult patients with type 1 diabetes.
Type 1 diabetes is a form of diabetes characterized by the body’s inability to produce insulin, leading to elevated blood glucose levels. Its pathogenesis involves the autoimmune destruction of pancreatic beta cells responsible for insulin production, with causes potentially including a combination of genetic and environmental factors. In the United States, approximately 1.25 million people have type 1 diabetes, including about 193,000 patients under the age of 20. Despite treatment with insulin therapy, approximately 70% of patients with type 1 diabetes fail to achieve the target glycated hemoglobin (A1C) level of less than 7.0%. Consequently, there is a substantial unmet need for novel oral agents that can be used in combination with insulin.
Zynquista is a small-molecule, investigational oral dual inhibitor of SGLT (sodium-glucose transport proteins)-1 and SGLT-2, developed in collaboration between Sanofi and Lexicon Pharmaceuticals, a partner of the WuXi AppTec Group.SGLT-1 and SGLT-2 respectively affect the absorption and clearance of sugar (glucose) in the intestine and kidneys. By modulating the activity of these two proteins, Zynquista improves glycemic control and provides additional clinical benefits. SGLT-2 inhibitors are commonly used in the treatment of type 2 diabetes.
The new drug application for Zynquista is based on data from the inTandem clinical trials, which include three Phase 3 clinical trials.The safety and efficacy of Zynquista were evaluated in approximately 3,000 adult patients whose blood glucose was poorly controlled with insulin alone. In the inTandem1 trial, Zynquista met the primary endpoint of change in HbA1c levels from baseline to 24 weeks. The changes in HbA1c levels were −0.43% for the 200 mg dose, −0.49% for the 400 mg dose, and −0.08% for placebo. The inTandem2 trial yielded similar results. The third trial, inTandem3, enrolled 1,405 patients with type 1 diabetes who had baseline HbA1c levels between 7% and 11%. This randomized, double-blind study demonstrated that after 24 weeks of treatment, 400 mg of Zynquista reduced baseline HbA1c by 0.79%, compared with a reduction of 0.33% in the placebo group (p<0.001). The inTandem3 trial met its statistically significant primary endpoint, and the results were published in the New England Journal of Medicine last September.
Dr. Jorge Insuasty, Senior Vice President and Head of Global Development at Sanofi, said: “If approved, Zynquista will become the first oral antidiabetic drug in the United States to be used in combination with insulin for the treatment of adult patients with type 1 diabetes."We look forward to working with the FDA through the review process, in hopes of bringing this drug to adult patients with type 1 diabetes in the United States."
"After decades, the treatment of type 1 diabetes is beginning to undergo significant changes. If approved, our dual SGLT-1 and SGLT-2 inhibitor Zynquista will become the first oral therapy used in combination with insulin to improve glycemic control and outcomes in adult patients with type 1 diabetes in the United States," said Dr. Pablo Lapuerta, Executive Vice President and Chief Medical Officer at Lexicon. "The acceptance of the NDA application brings us one step closer to providing meaningful therapies for patients with type 1 diabetes, and we look forward to continuing close collaboration with the FDA during the review process."
Under the PDUFA, the FDA’s target action date is expected to be March 22, 2019. Sanofi also submitted a regulatory application to the European Medicines Agency (EMA) earlier this year. Lexicon is currently conducting Phase 3 clinical trials of Zynquista for type 2 diabetes.
We look forward to the imminent approval of Zynquista, bringing new treatment options for patients with diabetes and helping them actively and effectively manage their blood glucose levels.
References:
[1] FDA to review Zynquista? (sotagliflozin) as potential treatment for type 1 diabetes
[2] FDA Accepts Zynquista NDA for Type 1 Diabetes
[3] Overall Numbers, Diabetes and Prediabetes
[4] Lexicon Pharmaceuticals Official Website
[5] New England Journal of Medicine Publishes Data from Phase 3 inTandem3 Study of Sotagliflozin in Patients with Type 1 Diabetes