Detailed results from a phase III test of Astrazeneca plc's Farxiga (dapagliflozin) found that adding the drug to standard of care in patients with chronic kidney disease (CKD) reduced a composite measure of worsening of renal function or risk of cardiovascular (CV) or renal death by 39% compared to placebo (p<0.0001).
The data, an expansion on earlier top-line reporting from the trial, showed the benefit in patients with CKD stages 2-4 and elevated urinary albumin excretion. Farxiga's benefit with SOC was consistent in patients both with and without type 2 diabetes (T2D), one of the most common causes of CKD, a condition that affects nearly 700 million people worldwide.
The result was a win for Farxiga, a SGLT2 inhibitor that in May became the first drug in its class to be approved to reduce the risk of CV death and hospitalization for heart failure patients with reduced ejection fraction.
“Slowing the progression of kidney failure with diabetes present or not will benefit many differing types of CKD patients, and may also impact outcomes in patients after renal transplantation,” said Paul Billings, chief medical officer and senior vice president for medical affairs at Natera Inc., a San Carlos, Calif.-based company that provides testing products to improve the care of patients with CKD.
But the trial results could also bolster the standing of Farxiga’s chief competitor in the class, Mizuho Securities USA managing director Vamil Divan said. That competitor, Jardiance (empagliflozin, Boehringer Ingelheim International GmbH and Eli Lilly and Co.), is now the subject of a phase III trial of its own in CKD patients, Empa-Kidney. That trial, which started in January 2019, is slated to be complete in June 2022. The SGLT2 inhibitor Invokana (canagliflozin, Johnson & Johnson) has also been shown to reduce the risk of both kidney failure and cardiovascular events in patients with T2D and CKD, irrespective of baseline HbA1c.
Astrazeneca's trial, called Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) was stopped early in March following a recommendation from an independent data monitoring committee due to overwhelming efficacy.
The primary composite endpoint for DAPA-CKD was a greater than or equal to 50% sustained decline in estimated glomerular filtration rate (eGFR), onset of end-stage kidney disease and CV or renal death. The absolute risk reduction was 5.3% over the median time in the study of 2.4 years. The trial also met all of its secondary endpoints, including significantly reducing death from any cause by 31%, with an absolute risk reduction of 2.1% vs. placebo (p=0.0035).
Co-chairs of the study and its executive committee were David Wheeler, a professor at University College London, and Hiddo Heerspink, a professor at University Medical Center Groningen, the Netherlands. Together, they called the results a "remarkable" development for patients with CKD, with "the potential to transform the standard of care" for them.
Astrazeneca's head of biopharmaceuticals R&D, Mene Pangalos, said the data made Farxiga the first SGLT2 inhibitor proven to "significantly prolong the survival" of patients with CKD. Farxiga is also first in its class "to demonstrate benefit in treating both heart failure and chronic kidney disease in patients with and without type 2 diabetes, and reduce the risk of hospitalization for heart failure and nephropathy in type 2 diabetes," he said.
Farxiga's safety profile, presented with the detailed results of the DAPA-CKD study on Aug. 30 as part of the ESC Congress, appeared to be in line with prior results.
In the U.S., Farxiga is approved as an adjunct to diet and exercise to improve glycemic control in adults with T2D and to reduce the risk of hospitalization for heart failure in adults with T2D and established CV disease or multiple CV risk factors. The drug generated $1.54 billion in global revenue in 2019, an 11% increase from its 2018 haul of $1.39 billion. Sales of the medicine are expected to continue climbing through 2026, according to a consensus forecast.
American depository receipts for Astrazeneca (NYSE:AZN) rose 31 cents, or 0.6%, to $56 on Aug. 31. Year to date, the ADSs are up 11.7%.