Dapagliflozin Meets Primary End Point in Phase 3 Trial, Reduces Risk of Cardiovascular Death and Worsening Heart Failure

Dapagliflozin, sold as Farxiga, reduced the risk of cardiovascular death and worsening heart failure (HF) in a phase 3 trial among patients with preserved ejection fraction, which until recently have lacked treatment options.

In a statement released early today, officials from AstraZeneca said the DELIVER trial had met its primary endpoint, which was a composite of the time to first occurrence of cardiovascular (CV) death, hospitalization for HF, or an urgent HF visit.

Heart failure affects 64 million people globally and is associated with increased morbidity and mortality. Ejection fraction (EF), a measurement of the percentage of blood leaving the heart each time it contracts, has several categories of HF related to it, which include HF with reduced EF (below 40%), HF with mildly reduced EF (41% to 49%), and preserved EF (50% or above). Patients in DELIVER had EF greater than 40%.

Dapagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor, one of a class of drugs first developed to treat type 2 diabetes (T2D) that has proven useful in treating multiple cardiometabolic conditions. In May 2020, the drug was approved in the United States to treat heart failure with reduced EF, and in April 2021, the FDA approved dapagliflozin to slow kidney decline, kidney failure, and cardiovascular death for adults with chronic kidney disease (CKD).

Until recently, treating HF with preserved ejection fraction has long been an area of unmet need. The FDA first approved Entresto (valsartan/sacubitril) despite the fact that it narrowly missed achieving superiority in a critical phase 3 trial; instead, regulators relied on evidence from subsets across several studies involving patients with left ventricle EF above 45%.

In February, FDA approved the SGLT2 inhibitor empagliflozin to treat HFpEF based on the EMPEROR-Preserved study, which found that empagliflozin is effective in patients with EF up to 65%.

Now, it appears that patients and providers may soon have another choice for treating HFpEF.

“We are delighted to have met the primary endpoint in the patient population which has few treatment options,” said Scott Solomon, MD, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital and principal investigator of the phase 3 trial. “The results of DELIVER extend the benefit of dapagliflozin to the full spectrum of patients with heart failure.”

The safety and tolerability of dapagliflozin in the phase 3 trial were consistent with the safety profile of the medicine. The full trial results will be presented at a future medical meeting and regulatory submissions will come in the next months.

“Today’s groundbreaking results coupled with those from the DAPA-HF trial show that Farxiga is effective in treating heart failure regardless of ejection fraction,” said Mene Pangalos, the executive vice presdient of BioPharmaceuticals R&D and AstraZeneca.

Reference

FARXIGA met primary endpoint in DELIVER phase III trial, reducing risk of cardiovascular death or worsening heart failure in patients with preserved ejection fraction. News Release. AstraZeneca. May 5, 2022. Accessed May 5, 2022. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2022/farxiga-met-primary-endpoint-in-deliver-phase-III-trial.html