AstraZeneca ramps up Farxiga push in new kidney disease label as it uncovers the challenges of this 'silent disease'

Like the business end of an iceberg, the majority of CKD (chronic kidney disease) patients go undiagnosed until damage is done.

That’s according to a new study funded by AstraZeneca, which markets the blockbuster metabolic and heart disease drug Farxiga for CKD. The company’s take on the study: Prompt testing, diagnosis and treatment will help a patient (and healthcare professionals) steer clear of morbidity and massive healthcare costs for this silent disease.

“There is considerable public health potential in diagnosing CKD using widely available low-cost testing, as well as providing treatments to those currently diagnosed,” said Helen Yeh, vice president, CVRM therapy area biopharmaceuticals medical at AZ, in an interview.

AstraZeneca’s drug was first approved to lower blood sugar levels in patients with Type 2 diabetes all the way back in 2014. In the past two years, however, Farxiga has been adding label expansions in a bid to beef up the blockbuster, with its FDA approval on CKD last year a potential new major money spinner for the med.

The CArdioREnal and MEtabolic (CaReMe) study, published in The Lancet Regional Health – Europe, involving 2.4 million patients in 11 countries, found that two out of three of those identified to have CKD had not been diagnosed, putting them at high risk of morbidity and mortality.

According to the study, 1 in 10 adults in Europe, Canada and Israel likely have CKD, and between 6% and 9% of them die each year, with cardiorenal (CKD or heart failure) events being a major contributor to morbidity and mortality. 

“These findings illustrate the considerable burden and unmet need of CKD affecting some 10% of the adult population,” said Yeh.

The study’s principal investigator, Navdeep Tangri, M.D., professor of medicine in the Department of Medicine and Community Health Sciences, University of Manitoba, explained that the study supports an intuition he had had as a clinical physician: that morbidity and healthcare costs associated with CKD are driven by the “salt and water” cardiorenal events like heart failure and CKD progression, and not by atherosclerotic CKD events like MI/IS (myocardial infarction or ischemic stroke), the latter being related to lipids and vascular stiffness.

According to Tangri, the study illustrates how cardiorenal outcomes generate three- to fourfold higher costs for patients than do MI/IS, which tend to happen to CKD patients because of comorbidity with diabetes and high blood pressure.

“These results are of great value because the solution for cardiorenal syndrome—early diagnosis and treatment—is easy,” he said. “And we are really blessed because we have multiple, great treatments for cardiorenal events, including the SGLT2 inhibitors and non-steroidal MRAs. And we have GLP1 antagonists like (Novo Nordisk’s) injectable semaglutide Ozempic, which is great for MI/IS.”

He added that another important takeaway from the study is the need to focus on measured CKD, not merely diagnosed disease (since only a third of patients are in the latter category).

He also explained that the issue of under-diagnosis actually stems from "decades of futility about diagnosis, because of not having CKD specific treatments. Therefore, CKD tended to be lumped as diabetic nephropathy or hypertensive kidney disease—and treated as a complication of diabetes and hypertension rather than a stand-alone disease.”

Yeh added that the study, generally, underscores the urgent unmet need in diagnosing and screening people globally for CKD. “Our hope is that providing this data will encourage policymakers, HCPs, patients and the broader health community to prioritize CKD screening and diagnosis.”

In 2020, Farxiga was the first drug in the SGLT2 inhibitor class to be approved for use in systolic heart failure, regardless of whether the patient had diabetes, which helped it close the gap with market leader Eli Lilly and Boehringer Ingelheims’s Jardiance (empagliflozin). Sales then climbed 30% to almost $2 billion, and 60% to $1.36 billion in the first half of 2021. Farxiga, now neck and neck with Jardiance for heart failure, was approved in 2021 for CKD in the U.S. and EU.

Jardiance had controlled 60% market share in Type 2 diabetes, driving monster sales for the brand—it had been the top-selling drug in the SGLT2 inhibitor class, with sales of almost $3 billion in 2019 because of an attractive side effect profile versus J&J’s Invokana (canagliflozin).

AZ’s drug, after winning approval in CKD, delivered revenue growth of 67% year over year, reaching $1 billion in quarterly sales for the first time during the first three months of 2022. Invokana, meanwhile, is approved only in diabetic kidney disease. To get the message out to Type 2 diabetes patients about Farxiga’s ability to dampen the comorbidity “crosstalk” between kidney and heart, AZ launched a “take aim” themed TV push earlier this year.

Meanwhile, in markets where AZ has launched Farxiga in CKD, the drug has captured market share of between 70% and 90%, Ruud Dobber, AZ’s biopharmaceuticals business head, told investors earlier this year.