AstraZeneca has announced positive full results from the DECLARE-TIMI 58 cardiovascular (CV) outcomes trial (CVOT) for Farxiga (dapagliflozin).
The data were presented as a late-breaking abstract (#19485) at the American Heart Association (AHA) Scientific Sessions 2018 in Chicago, Illinois, USA, and simultaneously published in the New England Journal of Medicine.
Results from DECLARE-TIMI 58, the largest SGLT2 inhibitor (SGLT2i) CVOT conducted to date, including more than 17,000 patients across 33 countries, showed that Farxiga significantly reduced the risk of hospitalisation for heart failure (hHF) or CV death composite vs. placebo by 17% (4.9% vs. 5.8%; HR 0.83 [95% CI 0.73-0.95], p=0.005), one of the two primary efficacy endpoints.
The reduction in hHF or CV death was consistent across the entire patient population, which included those with CV risk factors and those with established CV disease.
Additionally, there were fewer major adverse cardiovascular events (MACE) observed with Farxiga for the other primary efficacy endpoint, however this did not reach statistical significance (8.8% for Farxiga vs. 9.4% for placebo; HR 0.93 [95% CI 0.84-1.03], p=0.17).
DECLARE-TIMI 58 also confirmed the well-established safety profile for Farxiga, which met the primary safety endpoint of non-inferiority vs. placebo, demonstrating no increase in the composite of MACE, defined as CV death, heart attack (myocardial infarction), or stroke.
Further, on other relevant safety measures, the trial showed no imbalance with Farxiga vs. placebo in amputations (1.4% vs. 1.3%), fractures (5.3% vs. 5.1%), bladder cancer (0.3% vs. 0.5%) or Fournier’s gangrene (1 case vs. 5 cases). The respective incidences of diabetic ketoacidosis (0.3% vs. 0.1%) and genital infections (0.9% vs. 0.1%) were rare.
Elisabeth Björk, Vice President, Head of Cardiovascular, Renal and Metabolism, Global Medicines Development, said: “These positive results are clinically relevant to the 425 million people worldwide living with diabetes, of whom those with T2D have a two-to-five times greater risk of heart failure along with an increased risk of a heart attack or stroke.
“Heart failure survival rates are only 50% after five years from diagnosis, which is why these new findings are so important in broadening our understanding of how to go beyond blood glucose so we may better address this serious and often overlooked cardiovascular complication.”