Farxiga back on level pegging in heart failure

The FDA has approved AstraZeneca’s SGLT2 inhibitor Farxiga as a treatment candidate for all patients with heart failure, putting the drug back in contention with rival Jardiance from Boehringer Ingelheim and Eli Lilly.

Farxiga (dapagliflozin) – known as Forxiga in some markets – has been cleared to reduce the risk of cardiovascular death, hospitalisation for heart failure, and urgent heart failure visits in adult HF patients – regardless of their level of left ventricular ejection fraction (LVEF).

AZ’s drug was the first in the class to be approved to treat heart failure with reduced ejection fraction (HFrEF), but fell behind Jardiance (empagliflozin) when Boehringer and Lilly’s drug was approved for both HFrEF and heart failure with preserved ejection fraction (HFpEF) a year ago.

The FDA approval is based on the DELIVER trial, which showed that treatment with Farxiga led to an 18% reduction in cardiovascular death or worsening heart failure in patients with both mildly reduced and preserved ejection fraction (EF).

Ejection fraction is a measure of how much blood the left ventricle of the heart pumps out with each contraction, with the normal range around 50% to 75%.

Around half of the seven million heart patients with heart failure in the US have EF that is either mildly reduced or preserved, so the label change dramatically expands the eligible patient population for AZ’s drug.

According to AZ, Farxiga is the first drug to show a mortality benefit “across the full ejection fraction range.”

It’s worth noting that Farxiga – which is also approved for type 2 diabetes, as well as chronic kidney disease (CKD) – has been growing nicely despite lagging Jardiance in the all-comer heart failure population, mainly because it reached the market first in the CKD category.

First-quarter sales came in at $1.3 billion, up 39%, reinforcing its position as AZ’s top cardiovascular, renal, and metabolism (CVRM) product. Lilly and Boehringer are due to hear from the FDA on Jardiance as a CKD therapy later this year, and have an first-in-class win for an SGLT2 drug in the acute heart failure setting.

Also approved for both HFrEF and HFpEF is Novartis’ blockbuster Entresto (sacubitril/valsartan), although its data in the latter category looks a little weaker than its SGLT2 competitors. However, with different mechanisms of action there is potential for combination use.

AZ is also working on a combination of dapagliflozin with endothelin A receptor antagonist zibotentan in CKD and liver cirrhosis that has reached phase 2, with a decision on phase 3 expected later this year.