Dapagliflozin Meets Primary Endpoint in Study, Reducing Risk of CVD Death or Worsening HF

Results from the DELIVER and DAPA-HF phase 3 trials demonstrate AstraZeneca’s Farxiga’s efficacy in heart failure, regardless of ejection fraction.

Results from the DELIVER phase 3 trial of dapagliflozin (Farxiga) showed that the drug reached a clinically meaningful and statistically significant reduction in the primary composite endpoint of cardiovascular (CV) death or worsening heart failure (HF), AstraZeneca said in a statement.

“We are delighted to have met the primary endpoint in this patient population, which has few treatment options. DELIVER is the largest and broadest trial to date in heart failure with mildly reduced or preserved ejection fraction,” Scott Solomon, MD, professor of medicine at Harvard Medical School and Women’s Hospital, said in a statement. “The results of DELIVER extend the benefit of dapagliflozin to the full spectrum of patients with heart failure.”.

The DELIVER study was designed to evaluate the efficacy of dapagliflozin in the treatment of individuals with HF with left ventricular ejection fraction greater than 40% with or without type 2 diabetes (T2D) compared with the placebo. DELIVER is the largest clinical trial to date for individuals with HF and ejection fraction (EF) above 40%, and it included 6263 individuals.

Dapagliflozin was given once daily, in addition to background therapy, which is care for all other comorbidities, including diabetes and hypertension.

The primary endpoint was the time to first occurrence of CV death, hospitalization for HF, or urgent HF visit. The secondary endpoint included the total number of HF events, including change from baseline in the total symptom score of the Kansas City Cardiomyopathy Questionnaire at 8 months, HF visit and CV death or hospitalization for HF, , time to the occurrence of CV death, and time to the occurrence of death from any cause.

“Today’s groundbreaking results coupled with those from the DAPA-HF trial show that dapagliflozin is effective in treating heart failure, regardless of ejection fraction. These data build upon our previous studies demonstrating cardiorenal protection across patients with either diabetes, chronic kidney disease or heart failure,” Mene Pangalos, executive vice president of BioPharmaceuticals research and development at AstraZeneca, said in the statement.

The safety and tolerability profile of dapagliflozin in the DELIVER phase 3 trial were consistent with the well-established safety profile for the drug. The most common reported adverse events were female genital mycotic infections, nasopharyngitis, and urinary tract infections.

The full results of the study will be submitted for presentation at a forthcoming medical meeting, and regulatory submissions will be made in the coming months.

Dapagliflozin is indicated for as an adjunct to diet and exercise to improve glycemic control in adults with T2D mellitus; to reduce the risk of hospitalization for HF in adults with T2D mellitus and either established CV disease or multiple CV risk factors; to reduce the risk of CV death and hospitalization for HF in adults with HF with reduced EF; to reduce the risk of sustained eGFR decline, end-state kidney disease, cardiovascular death, and hospitalization for HF in adults with chronic kidney disease at risk of progression.

Reference

Results from the DELIVER and DAPA-HF phase III trials demonstrate Farxiga’s efficacy in heart failure regardless of ejection fraction. AstraZeneca. News release. 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