15 November 2018 - - Anglo-Swedish pharmaceutical company AstraZeneca (OTC: AZNCF) has received positive full results from the DECLARE-TIMI 58 cardiovascular outcomes trial for Farxiga (dapagliflozin), the company said.

The data were presented as a late-breaking abstract (#19485) at the American Heart Association Scientific Sessions 2018 in Chicago, IL, and simultaneously published in the New England Journal of Medicine (NEJM).

Results from DECLARE-TIMI 58, the largest SGLT-2 inhibitor (SGLT-2i) CVOT conducted to date, including more than 17,000 patients across 33 countries, showed that Farxiga significantly reduced the risk of hospitalization for heart failure 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.1 Farxiga is not indicated to reduce the risk of CV events or hHF.

Additionally, there were fewer major adverse cardiovascular events 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.

Although secondary endpoints were only nominally significant, the renal composite endpoint showed that Farxiga reduced the rate of new or worsening nephropathy by 24% vs. placebo across the broad patient population studied (4.3% vs. 5.6%; HR 0.76 [95% CI 0.67-0.87]), and there were fewer all-cause mortality events with Farxiga vs. placebo (6.2% vs. 6.6%; HR 0.93 [95% CI 0.82-1.04]).

DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI-58 is an AstraZeneca-sponsored, randomised, double-blinded, placebo-controlled, multicenter trial designed to evaluate the effect of Farxiga compared with placebo on CV outcomes in adults with T2D at risk of CV events, including patients with multiple CV risk factors or established CV disease.

DECLARE included more than 17,000 patients across 882 sites in 33 countries and was independently run in collaboration with academic investigators from the TIMI study group (Boston, USA) and the Hadassah Hebrew University Medical Center (Jerusalem, Israel).

DECLARE is part of the extensive DapaCare clinical program for Farxiga, which will enroll patients in randomized clinical trials, including a wide range of mechanistic studies, and is supported by a multinational real-world evidence study (CVD-REAL).

The DapaCare clinical program will generate data across a spectrum of people with CV risk factors, established CV disease and varying stages of renal disease, both with and without T2D. DECLARE is paving the way for three Phase III trials: Dapa-HF, DELIVER and Dapa-CKD.