FDA Breakthrough Therapy Designation for SGLT2i in chronic kidney disease
The FDA has granted Breakthrough Therapy Designation to the SGLT2 inhibitor dapagliflozin for the treatment of patients with chronic kidney disease (CKD). This decision is based on evidence from the DAPA-CKD trial. In this trial, treatment with dapagliflozin reduced the composite endpoint of worsening of renal function or risk of CV or renal death by 39% compared to placebo in CKD patients. Also, death from any cause was reduced by 31% in the group treated with dapagliflozin compared to the placebo group.
The FDA’s Breakthrough Therapy Designation has been designed to accelerate development and regulatory review of potential new medications that are intended for the treatment of serious conditions and address a unmet medical need.
Dapagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in T2DM patients and reduce the risk of hospitalization for HF in T2DM patients with established CVD or with multiple CV risk factors. In May 2020, dapagliflozin was approved to reduce risk of CV death and hospitalization for HF in HFrEF patients with and without T2DM.
The DAPA-CKD trial is an international, multi-center, randomized, double-blinded trial of 4304 patients. It evaluated the efficacy of dapagliflozin compared to placebo in patients with CKD stages 2-4, elevated urinary albumin excretion, with and without T2DM. The primary composite endpoint was worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of ESKD and death from CV or renal cause). Secondary endpoints included time to first occurrence of the renal composite, the composite of CV death or hospitalization for HF, and death from any cause.