Dapagliflozin earns breakthrough therapy designation for CKD with, without type 2 diabetes
The FDA granted breakthrough therapy designation to the SGLT2 inhibitor dapagliflozin for adults with chronic kidney disease with and without type 2 diabetes, according to an industry press release.
The decision follows findings from the DAPA-CKD trial, published in September in The New England Journal of Medicine, that demonstrated treatment with dapagliflozin (Farxiga, AstraZeneca) reduced risks for worsening renal function and death due to cardiovascular disease or renal disease in patients with CKD, both with and without type 2 diabetes. As Healio previously reported, AstraZeneca stated in March that the DAPA-CKD trial would be stopped early, per recommendation from the independent data monitoring committee, after investigators reported an “overwhelming benefit” for reduction in worsening renal function or renal death compared with placebo.
“There is a serious, unmet need for better and earlier treatment options for patients with chronic kidney disease,” Mene Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said in the release. “Following the ground-breaking DAPA-CKD results, the breakthrough therapy designation is further testament to Farxiga’s potential to slow the progression of chronic kidney disease. We look forward to working with the FDA to make Farxiga available to patients as quickly as possible.”
DAPA-CKD findings, initially presented at the European Society of Cardiology Congress in August and again at the European Association for the Study of Diabetes in September, showed treatment with dapagliflozin significantly reduced renal failure, CV death or hospitalization for heart failure, and prolonged survival among adults with CKD with and without type 2 diabetes.
During a median 2.4 years, the primary outcome — a composite of sustained decline in eGFR of at least 50%, end-stage renal disease or death due to kidney-related or CV causes — occurred in 197 participants (9.2%) in the dapagliflozin group and 312 participants (14.5%) in the placebo group, meaning patients in the dapagliflozin group had a 39% lower risk for the primary endpoint compared with the placebo group (HR = 0.61; 95% CI, 0.51-0.72), with a number needed to treat to prevent one primary outcome event of 19.
In a series of secondary analyses, participants in the dapagliflozin group also had a 44% lower risk for the combined renal outcome of sustained decline in eGFR of 50% or more, ESRD or renal death — but not CV death — compared with placebo.
All-cause mortality was significantly different between the dapagliflozin and placebo groups (4.7% vs. 6.8%), with an HR of 0.69 (95% CI, 0.53-0.88), meaning those in the dapagliflozin group had a 31% lower risk for death from any cause.
In May, dapagliflozin was approved to reduce the risk of CV death and hospitalization for HF for adults with HF with reduced ejection fraction, with and without type 2 diabetes.
Breakthrough therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. According to the FDA, criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.