FDA Approves Canagliflozin to Prevent Kidney Failure, Hospitalization for Heart Failure

Canagliflozin, the first of a wave of drugs that treated type 2 diabetes (T2D) by shipping excess blood sugar out of the body through urine, today received FDA approval to harness that unique mechanism to prevent kidney failure—a debilitating side effect that is one of the most expensive conditions in Medicare.

Based on results from the CREDENCE trial, FDA approved canagliflozin to treat diabetic kidney disease and to reduce the risk of hospitalization for heart failure for the roughly 1 in 3 patients with T2D who also have diabetic kidney disease. The CREDENCE study, presented in April, showed that canagliflozin reduced the risk of renal failure or death by 30% in this population.

The company announced the new indication in a statement.

“This significant advancement addresses serious unmet needs and could change the trajectory of care for the many millions of patients living with type 2 diabetes and diabetic kidney disease,” said James List, MD, PhD, global therapeutic area head, Cardiovascular and Metabolism, Janssen Research and Development, LLC.

Sold as Invokana by Janssen, canagliflozin was approved in 2013 as the first of the sodium glucose co-transporter 2 (SGLT2) inhibitors, a class of diabetes drugs that represented a departure in methods to control glycated hemoglobin (A1C) that could work alongside existing diabetes therapies.

Requirements of a 2008 FDA directive called on Janssen and other drug manufacturers to conduct large cardiovascular outcomes trials to show the drugs were safe, but this ended up showing that the drugs’ volume-depleting qualities had other benefits, notably on heart failure. The SGLT2 inhibitors were the first drugs to lower A1C shown to reduce cardiovascular events when rival empagliflozin (Jardiance) was shown to reduce the risk of CV death by 38%. This was later shown to be a class effect; canagliflozin was shown to reduce CV events in 2017 through the CANVAS trial.

In June, at the meeting of the American Diabetes Association, additional results from CREDENCE showed that canagliflozin prevented renal decline in those with T2D who had been diagnosed with CV disease or had already experienced an event such as a heart attack or stroke, known as secondary prevention, as well as those who had neither, known as primary prevention.

Janssen and researchers on CREDENCE have both described the use of canagliflozin to prevent renal failure as the first breakthrough in treating chronic kidney disease in 20 years. Preventing patients from progressing to end-stage renal disease would potentially yield huge savings; few conditions strain the US health system as much as end-stage renal disease, which affects 750,000 individuals at a cost of $89,000 per person. It is anticipated that without a way to halt progression, more people will need dialysis because more Americans are becoming obese.

T2D is the leading cause of kidney disease in the United States, and the fifth fastest-rising cause of death worldwide.