AstraZeneca’s Diabetes Drug Farxiga Decreases Risk of Cardiovascular Disease

AstraZeneca announced positive results from its Phase III DECLARE-TIMI 58 cardiovascular outcomes clinical trial of Farxiga (dapagliflozin).

The drug, which is used to treat diabetes, was being evaluated compared to placebo for its effects on cardiovascular outcomes, or major adverse cardiovascular events (MACE). The trial evaluated more than 17,000 patients across 882 sites in 33 countries and compared the effect of Farxiga compared to placebo on cardiovascular outcomes in adults with type 2 diabetes at risk of cardiovascular events.

“Farxiga has achieved a statistically significant and clinically important reduction in hospitalization for heart failure or CV death in a broad range of patients with type 2 diabetes and cardiovascular risk,” said Elisabeth Bjork, AstraZeneca’s vice president, Head of Cardiovascular, Renal and Metabolism, Global Medicines Development, in a statement. “The results from this landmark trial are especially important since heart failure is an early and frequent complication of diabetes and associated with hospitalizations that result in a considerable societal and economic burden.”

The results weren’t completely positive, however. The trial met its primary safety endpoint of non-inferiority for major adverse cardiovascular events. It also hit a statistically significant decrease in the composite endpoint of hospitalization for heart failure (hHF) or cardiovascular death, one of the two primary efficacy endpoints for the trial. But, although the company spun this as something of a positive, because there were fewer major adverse cardiovascular events observed, it did not meet statistical significance, thus failing to hit that second primary efficacy endpoint.

Reuters notes, “The failure to achieve a more convincing reduction in CV events — such as heart attacks and strokes — may be seen as disappointing. But Ludovic Helfgott, AstraZeneca’s head of CV and metabolic diseases, believes the overall data suggests Farxiga could win expanded approval as a diabetes drug with proven heart benefits in a wide range of patients.”

Helfgott told Reuters, “We have demonstrated with Declare that we have a cardiovascular outcome in a broad population and we believe that is something that needs to be recognized by regulators and the clinical community. We are expecting to have a new label by the end of next year.”

The drug’s market competitors include Eli Lilly and Boehringer Ingelheim’s Jardiance and Novo Nordisk’s Victoza, which have already proven in trials to show improved cardiovascular outcomes. However, AstraZeneca’s study takes this a step further, showing Farxiga helped decrease cardiovascular events in patients that don’t have established cardiovascular disease.

In a note to clients, Jack Scannel, an analyst with UBS, wrote, “This should provide a degree of commercial differentiation.”

Analysts’ consensus predicts Farxiga to have peak annual sales of $2.7 billion by 2023. Projected sales for this year are $1.4 billion.

“The DECLARE-TIMI 58 results offer compelling evidence that dapagliflozin helps to address an important medical need among a diverse group of patients with type 2 diabetes by reducing the composite of hospitalization for heart failure or CV death, with a safety profile supportive of broad use,” said Stephen Wiviott, senior investigator with the TIMI study group, co-principal investigator of the trial, and researcher at Brigham and Women’s Hospital and Harvard Medical School.