AZ's Farxiga first in class to improve outcomes in heart failure

AstraZeneca has scored a major trial victory after its Farxiga (dapagliflozin) became the first drug in its class to show efficacy in heart failure, in patients with or without type-2 diabetes.

Farxiga is an SGLT2 class drug, which until now has been used to control blood sugar levels in patients with diabetes.

But in the DAPA-HF trial Farxiga met a primary composite endpoint of a statistically significant and clinically meaningful reduction of cardiovascular death or worsening of heart failure – defined as hospitalisation or an urgent heart failure visit – compared with placebo.

The trial was conducted in patients with reduced ejection fraction on standard of care treatment, including those with and without type-2 diabetes.

The safety profile of Farxiga in the DAPA-HF trial was consistent with the well-established safety profile of the medicine.

DAPA-HF is the first heart failure outcomes trial with an SGLT2 inhibitor investigating the treatment of heart failure in adults with reduced ejection fraction (HFrEF) on top of standard of care in patients with and without type-2 diabetes.

Standard therapy includes medicines such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, mineralocorticoid-receptor antagonists and neprilysin inhibitors.

Results of DAPA-HF will be welcome after the FDA rejected Farxiga for use as a supplement to insulin adults with type-1 diabetes unable to control blood sugar with insulin alone.

AZ is not alone in trying to get an SGLT2 class drug approved in heart failure: Eli Lilly and Boehringer Ingelheim also have their rival Jardiance (empagliflozin) in phase 3 development, with results due next year.

Sanofi is also developing its SGLT2 sotagliflozin in type 2 diabetes patients with worsening heart failure, with results of the phase 3 SOLOIST-WHF trial due in 2021.

Farxiga is becoming increasingly important for AZ after the company’s sales revival following a prolonged slump caused by patent expiries on key blockbusters.

It is one of the company’s top 10 drugs by sales, increasing 14% to $726 million in the first half of the year, although this was slower than the growth seen in 2018 when sales grew at 30% to $1.39 billion.

This growth is likely to increase with a potential new label in heart failure, and an EU label update to include cardiovascular and kidney outcomes from the DECLARE-TIMI 58 trial.

Mene Pangalos, AZ’s executive vice president of BioPharmaceuticals R&D, said: “With the DAPA-HF trial, Farxiga becomes the first in its class to demonstrate efficacy and safety data for the treatment of patients with heart failure, with and without type-2 diabetes, on top of standard of care.

“Today, half of heart failure patients will die within five years of diagnosis and it remains one of the leading causes of hospitalisation. We look forward to discussing the results of DAPA-HF with health authorities as soon as possible.”