AstraZeneca's Dapagliflozin Meets Primary End Point in Heart Failure Trial

AstraZeneca announced today that the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin, sold as Farxiga, met the primary composite end point for patients enrolled in Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF), a phase 3 heart failure outcomes trial that explored whether the therapy that has reshaped care for type 2 diabetes (T2D) could do the same in heart failure.

DAPA-HF found that the SGLT2 inhibitor significantly reduced the risk of cardiovascular death or worsening of heart failure in patients with reduced ejection fraction (HFrEF) when added to standard of care, according to a statement from the drug maker. Notably, the 4744 patients randomized for the study include those with and without T2D.¹

Worsening of heart failure is defined as hospitalization or an equivalent event, such as an urgent heart failure visit, according to a trial design paper appearing earlier this year in the European Journal of Cardiology.¹ The topline results announced today do not specify if dapagliflozin’s effects on heart failure were similar in both populations; those results will be presented soon.

“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,” said Mene Pangalos, PhD, executive vice president, BioPharmaceuticals Research and Development at AstraZeneca.

“Today, half of heart failure patients will die within 5 years of diagnosis and it remains one of the leading causes of hospitalization. We look forward to discussing the results of DAPA-HF with health authorities as soon as possible,” he said.

Heart Failure: the Next Frontier for SGLT2 Class

Nearly 4 years ago, the diabetes care community was stunned when results from the EMPA-REG OUTCOME trial for empagliflozin (Jardiance, Eli Lilly/Boehringer Ingelheim) showed that the SGLT2 inhibitor was not only safe for T2D patients but in fact reduced the risk of cardiovascular death. AstraZeneca then added a second primary end point to its cardiovascular outcomes trial, DECLARE-TIMI 58, and results released in November 2018 showed that dapagliflozin significantly reduced the risk of hospitalization for heart failure.

In fact, across all 3 cardiovascular outcomes trials for SGLT2 inhibitors (the third being CANVAS for Janssen’s canagliflozin), much of the SGLT2 class effect appears driven by the drugs’ cardioprotective effects in heart failure, which has prompted the American College of Cardiology to encourage its members to prescribe the drugs for their patients. There has been a new wave of heart failure outcomes trials that could lead to new indications beyond T2D. Two other trials, DELIVER and DETERMINE, are studying dapagliflozin in heart failure patients with preserved ejection fraction (HFpEF).

Empagliflozin is being studied in patients with and without T2D the EMPEROR trials (EMPEROR-Preserved, EMPEROR-Reduced); in late June, the drug’s sponsors announced FDA had granted fast-track designation for a heart failure indication to allow for expedited review, although results from those trials are not expected until June 2020.

References

1. McMurray JJV, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Cardiol. 2019;21:665-675. doi:10.1002/ejhf.1432.