AstraZeneca Announces Detailed Phase 3 Results of Farxiga (Dapagliflozin), Showing 27% Reduction in Heart Failure Risk in Non-Diabetic Patients

Recently, AstraZeneca announced the detailed results of its Phase 3 clinical trial evaluating Farxiga (dapagliflozin), an SGLT2 inhibitor, in patients with heart failure at the European Society of Cardiology Congress (ESC 2019). In August this year, AstraZeneca had already announced that dapagliflozin met both the primary and key secondary endpoints in this trial. The newly released detailed data demonstrated that dapagliflozin reduced the risk of cardiovascular death and worsening heart failure to a comparable extent in patients without type 2 diabetes as in those with type 2 diabetes, providing robust evidence for further expanding the eligible patient population for dapagliflozin.

Heart failure is a life-threatening, serious condition caused by the heart's inability to pump sufficient blood to the rest of the body. There are approximately 64 million patients worldwide (half of whom have heart failure with reduced ejection fraction), and nearly half of these patients die within five years of diagnosis. Heart failure is one of the leading causes of hospitalization among adults aged 65 and older, representing a significant clinical and economic burden.

Dapagliflozin is a first-in-class oral SGLT2 inhibitor. It has received FDA approval, in conjunction with diet and exercise, to improve glycemic control in patients with type 2 diabetes mellitus, and it can also reduce their body weight and blood pressure. It has also been approved by the European Union for the treatment of patients with type 1 diabetes mellitus.

DAPA-HF was the first Phase 3 clinical trial to investigate the effects of SGLT2 inhibitors on the risk of death and disease worsening due to heart failure. The patients enrolled in this trial represented typical heart failure patients, with 45% having type 2 diabetes at baseline prior to treatment initiation. In this randomized, double-blind, multicenter, international Phase 3 clinical trial, patients with heart failure with reduced ejection fraction received either dapagliflozin or placebo in addition to standard therapy. The primary composite endpoint was worsening heart failure events (defined as hospitalization or emergency visit for heart failure) or cardiovascular death.

▲Primary Endpoint Results of the DAPA-HF Trial (Image source: Reference [2])

Detailed data presented at ESC 2019 demonstrated that dapagliflozin reduced the risk of worsening heart failure events and cardiovascular death by 26% in patients with heart failure (HR=0.74, 95% CI: 0.65–0.85, p=0.00001), including a 30% reduction in the risk of worsening heart failure and an 18% reduction in the risk of cardiovascular death. Furthermore, assessment of patient-reported heart failure symptoms using the KCCQ symptom scale indicated that dapagliflozin significantly improved these symptoms.

New drugs of the SGLT2 inhibitor class have demonstrated efficacy in reducing the risk of heart failure in patients with diabetes; therefore, industry attention has focused on the performance of dapagliflozin in non-diabetic patients. The published detailed subgroup results indicate that dapagliflozin reduces the risk of heart failure by 27% in patients without type 2 diabetes (HR=0.73, 95% CI: 0.60–0.88), which is comparable to the effect observed in patients with type 2 diabetes (HR=0.75, 95% CI: 0.63–0.90).

▲ Primary Endpoint Results in Subgroups of Heart Failure Patients With and Without Type 2 Diabetes (Image source: Reference [2])

Dr. Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, said, “Farxiga has already demonstrated strong efficacy in the treatment of type 2 diabetes. These exciting new findings highlight its potential to reduce the burden on heart failure patients, with or without type 2 diabetes.”

References:

[1] Detailed results from Phase III DAPA-HF trial showed Farxiga significantly reduced both the incidence of cardiovascular death and the worsening of heart failure. Retrieved September 1, 2019, from https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2019/detailed-results-from-phase-iii-dapa-hf-trial-showed-farxiga-significantly-reduced-both-the-incidence-of-cardiovascular-death-and-the-worsening-of-heart-failure-01092019.html

[2] Farxiga’s DAPA-HF trial at ESC. Retrieved September 1, 2019, from https://www.astrazeneca.com/content/dam/az/PDF/2019/AZN%20ESC%20DAPA-HF%202019.pdf

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