Detailed results presented at the European Society of Cardiology (ESC) congress from the Phase III DAPA-HF trial demonstrated that AstraZeneca's SGLT2 inhibitor Farxiga (dapagliflozin) plus standard of care lowered the incidence of both cardiovascular (CV) death and the worsening of heart failure by a significant 26% in patients with reduced ejection fraction (HFrEF), the company announced. Findings also showed a reduction in each of the individual components of the composite endpoint.
Principal investigator John McMurray suggested that "the most important finding of all is the benefit in patients without diabetes. This is truly a treatment for heart failure and not just a drug for diabetes."
The trial randomised 4744 HFrEF patients, with and without type 2 diabetes, to receive once-daily Farxiga or placebo, both in addition to standard of care, which could include ACE inhibitors, angiotensin II receptor blockers, beta blockers, mineralocorticoid-receptor antagonists and neprilysin inhibitors. The primary endpoint was the composite of a first episode of worsening heart failure, defined as hospitalisation or an urgent heart failure visit requiring intravenous therapy, or death from CV causes.
Over a median follow-up of 18.2 months, the primary outcome occurred in 16.3% of patients in the Farxiga group, versus 21.2% for placebo. When the components of the primary composite endpoint were analysed separately, results showed that 10% of participants receiving Farxiga and 13.7% of those on placebo experienced a first episode of worsening heart failure, translating to a 30% decreased risk. Meanwhile, 9.6% and 11.5% of patients, respectively, died from CV causes, reflecting an 18% lower risk for Farxiga.
In regards to safety, McMurray noted that "adverse events rarely required the discontinuation of treatment," and there was "no notable excess of any serious adverse event in the Farxiga group." Specifically, adverse events related to volume depletion occurred in 7.5% of participants in the trial's Farxiga arm, compared with 6.8% for placebo, while adverse events related to renal dysfunction occurred at rates of 6.5% and 7.2%, respectively, with no significant difference between groups. Researchers also said that cases of major hypoglycaemia and lower limb amputation and fracture were "infrequent and occurred at similar rates" in the two groups.
Ruud Dobber, president of AstraZeneca's BioPharmaceuticals division, said he anticipated filing the DAPA-HF data to US and European regulators during the second half of this year, with an expanded label approved six to 12 months after that.
Meanwhile, Deutsche Bank analysts suggested the DAPA-HF findings will likely lead to Farxiga becoming the new standard of care for heart failure in patients, both with and without diabetes. They added "we believe this represents an additional [$1 billion-$4 billion] market opportunity for the class, which is not reflected in consensus forecasts." Citi analysts called the results "stellar," adding they expect rapid uptake across the majority of heart failure patients with reduced ejection fraction.
Farxiga is currently indicated as monotherapy and as part of combination therapy to improve glycaemic control in adults with type 2 diabetes. However, in July, the FDA rejected AstraZeneca's filing to expand Farxiga's label to include use as an adjunct treatment to insulin for certain adults with type 1 diabetes.
Sales of the product jumped 11% year-over-year in the second quarter to $377 million, driven by growth in China and Europe.
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