Farxiga CKD Trial Stopped Early For Efficacy, Giving The SGLT2 Inhibitor An Edge
Executive Summary
A Phase III trial testing dapagliflozin in chronic kidney disease patients with and without diabetes was stopped early following a recommendation from an independent data monitoring committee.
A Phase III study testing AstraZeneca PLC's Farxiga (dapagliflozin) in patients with chronic kidney disease (CKD) will be stopped early due to efficacy, presenting a new commercial opportunity for the sodium glucose cotransporter 2 (SGLT2) inhibitor. The study enrolled patients with and without type 2 diabetes, suggesting a broad opportunity for Farxiga in CKD.
AstraZeneca, announcing the positive trial update on 30 March, said it would begin discussions with global regulatory authorities about the data and potential regulatory filing timeline. The results of the trial had been expected in 2021.
Farxiga, like other SGLT2 inhibitors, is approved for the treatment of glycemic control in type 2 diabetes patients. It is also approved to reduce the risk of hospitalization from heart failure in patients with type 2 diabetes and cardiovascular risk factors. It is pending at the US Food and Drug Administration for heart failure in a broader population, in adults with reduced ejection fraction (HFrEF) with and without type 2 diabetes, with action expected in the first half of the year. (Also see "AZ’s Farxiga Gets FDA Priority Review For Heart Failure" - Scrip, 6 Jan, 2020.)
AstraZeneca has been successfully building out its Farxiga franchise in new patient populations. Sales of Farxiga grew 11% in 2019 to $1.54bn. Farxiga competes with
Eli Lilly & Co.'s Jardiance (empagliflozin) and Johnson & Johnson's Invokana (canagliflozin), but while both of those drugs carry a cardiovascular risk-reduction claim in patients with diabetes, neither one has a broad heart failure indication in patients with and without type 2 diabetes.
Neither drug carries an indication in a broad CKD population either, although Invokana is approved to reduce hospitalization in heart failure patients with type 2 diabetes and to reduce the risk of end-stage kidney disease in patients with type 2 diabetes.
AstraZeneca said the DAPA-CKD trial was stopped early due to "overwhelming efficacy" based on the recommendation from an independent data monitoring committee.
Executive VP of biopharmaceuticals R&D Mene Pangalos said in a statement that CKD patients have limited treatment options, particularly those with type 2 diabetes, and asserted that Farxiga could change the management of CKD globally.
Deutsche Bank analyst Richard Parkes said approval broadly in CKD and heart failure would present significant labeling advantages for Farxiga over other SGLT2 inhibitors.
"Given that there are estimated to be more than 4 million patients diagnosed with CKD in the US alone and only half of these have diabetes, the additional opportunity for the class in CKD could reach $5bn globally," Parkes said. "Evaluation of the drug's benefits in patients with and without diabetes when data is presented will be key to assessing this potential."
The full results of the study will be presented at an upcoming medical meeting, AstraZeneca said. The primary endpoint of the trial is a composite of worsening of renal function or death (defined as a composite endpoint of ≥ 50% sustained decline in estimated glomerular filtration rate (eGFR), onset of end-stage kidney disease (ESKD) or cardiovascular (CV) or renal death) in patients with CKD irrespective of the presence of type 2 diabetes.
The randomized trial enrolled 4,245 patients and studied the efficacy of Farxiga 10mg compared to placebo in patients with CKD stages 2-4. The study is being conducted in 21 countries.
FDA has granted Farxiga fast track designation for slowing the progression of renal failure and prevention of cardiovascular and renal death in patients with CKD. The most common causes of CKD are diabetes, hypertension and glomerulonephritis.
Farxiga is also being tested in heart failure patients with preserved ejection fraction (HFpEF) in the DELIVER trial and in both HErEF and HFpEF patients in DETERMINE.
Farxiga is a key growth driver in AstraZeneca's cardiovascular/renal medicine (CVRM) business, which the company renamed in 2018 to reflect its expansion in renal disease outside of diabetes. (Also see "Next Up For AstraZeneca: Building Out In Renal Disease " - Scrip, 24 Oct, 2018.)
The company is also preparing for another renal launch, the HIF-PH inhibitor roxadustat, which is partnered with FibroGen Inc. and pending at the FDA. Biopharmaceuticals president Rudd Dobber talked to Scrip about the renal expansion plans at the J.P. Morgan Healthcare Conference in January. (Also see "AstraZeneca's Dobber On Ramping In Renal, Expanding In CV And Business Development " - Scrip, 21 Jan, 2020.)