FDA Approves Dapagliflozin for Chronic Kidney Disease

The US Food and Drug Administration (FDA) has approved dapagliflozin (Farxiga) for the reduced risk of kidney function decline, failure, and cardiovascular death and hospitalization for heart failure in at-risk adults with chronic kidney disease.

The approval, granted to AstraZeneca, is the newest indication for the SGLT-2 inhibitor therapy, which was originally approved for type 2 diabetes glycemic control 7 years ago and has been assessed for a litany of cardiometabolic, cardiovascular, and renal outcomes in the same subpopulations of originally treated patients.

The Drug

Dapagliflozin is an inhibitor of the sodium-glucose co-transporter 2 (SGLT2), designed to aid kidneys in lowering patient glucose levels.

The agent was previously approved as a combination therapy with diet and exercise for glycemic control in adults with type 2 diabetes, then—on the basis of DAPA-HF findings—was approved for the treatment of heart failure with reduced ejection fraction (HFrEF)—in adults regardless of diabetes status.

The FDA previously granted dapagliflozin Fast Track, Breakthrough Therapy, and Priority Review designations for the treatment of kidney- and cardiovascular-related outcomes in adults with chronic kidney disease.

The Data

The newest FDA indication for dapagliflozin was based on DAPA-CKD data previously published in The New England Journal of Medicine last October.

Investigators, led by Hiddo J.L. Heerspink, PhD, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, compared kidney outcomes and reduced cardiovascular deaths among 4304 patients with chronic kidney disease treated with either dapagliflozin or placebo.

The multicenter, double-blind trial sought a comparison of treatment arm participants who whose disease progress to a composite endpoint including ≥50% reduction in kidney function, progression to kidney failure, or death due to cardiovascular or kidney complications.

Heerspink and colleagues reported 197 of 2152 (9.2%) patients treated with dapagliflozin reached the composite endpoint, versus 312 of 2152 (14.5%) of patients on placebo.

Additionally, 138 patients on placebo were hospitalized or died during assessment, versus just 100 patients treated with dapagliflozin.

Reaction

Heerspink called the DAPA-CKD data “unprecedented results” when discussing the historic landmark of the first SGLT2 inhibitor approved for treating chronic kidney disease regardless of patient diabetes status.

“This transformational milestone provides patients and physicians with a new and effective treatment option for this often debilitating and life-threatening disease,” Heerspink said in a statement.

Mene Pangalos, executive vice president of BioPharmaceuticals R&D, went so far as to say the indication is “the most significant advancement in the treatment of chronic kidney disease” in 20-plus years.

“We’ve shown impressive efficacy for Farxiga in type-2 diabetes, heart failure with reduced ejection fraction and, most recently, chronic kidney disease and we are thrilled to be able to bring this medicine to millions of patients in the US,” Pangalos said.

Long before the expanded indicatiosn of dapagliflozin across cardiovascular, metabolic, and now renal outcomes, experts observed early data of comorbid benefit and predicted such an outcome with the diverse SGLT2 inhibitor drug class.

“I think it's really exciting to be able to have this tool in our toolkit for treating heart failure, and one that really spans across internal medicine—really uniting those of us who are in primary care, endocrinology and cardiology…to have a drug that might have multiple benefits,” Shaline Rao, MD, heart failure cardiologist and assistant profess at NYU Langone Health, told HCPLive in November 2019. “I think we really like to see that in future pharmacologic therapies where we're really able to address more than one condition where patients take so many medications, as is.”