The Food and Drug Administration has rejected AstraZeneca’s supplemental New Drug Application for the sodium-glucose cotransporter 2 inhibitor dapagliflozin (Farxiga) as an adjunct treatment to insulin in adult patients with type 1 diabetes.
The company said in a press statement that the FDA had issued a complete response letter regarding the application. No reason was given for the decision, but the company said it would work with the agency to discuss the next steps.
The once-daily therapy has been approved as both a monotherapy and combination therapy, as an adjunct to diet and exercise, for improving glycemic control in adults with type 2 diabetes who cannot achieve control with insulin alone. It also has additional demonstrated benefits of weight loss and reduction in blood pressure.
On March 25, 2019, the drug received its first approval for treatment of patients with type 1 diabetes when the European Commission gave it the green light for use in patients with a body mass index of 27 kg/m2 or more when insulin alone does not provide adequate glycemic control. Japan followed a few days later with its approval of the sodium-glucose cotransporter 2 inhibitor, also for type 1 disease in adults.
The approvals for type 1 diabetes in the European Union and Japan were based on data from the phase 3 DEPICT (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) trial program (DEPICT-1 and DEPICT-2), which showed that 5 mg dapagliflozin, taken daily as an oral adjunct to insulin in patients with hard-to-control type 1 disease, reduced blood glucose levels from baseline (the primary endpoint). Secondary endpoints – reductions in weight and total daily insulin use – were also achieved.
Dapagliflozin’s safety profile in the trials in patients with type 1 diabetes was consistent with that established in patients with type 2 disease. However, there was a higher number of cases of diabetic ketoacidosis events in patients who received dapagliflozin. Diabetic ketoacidosis is a known complication for adults with type 1 diabetes and is more prevalent in patients with type 1 disease than in those with type 2.