The study met the primary endpoint of non-inferiority on major adverse CV events (MACE), which is composed of a composite of CV death, nonfatal myocardial infarction or nonfatal stroke, compared to placebo.
“The VERTIS CV results add to the growing body of evidence regarding the clinical profile of ertugliflozin, including its safety in patients with a history of cardiovascular disease,” said Dr. Christopher P. Cannon, cardiologist at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School, the study’s lead author. “Although not a part of the hierarchical testing sequence, the results indicated the potential of ertugliflozin to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes and established cardiovascular disease.”
Overall, the primary MACE outcome was reported in 11.9% (n=653) of patients treated with STEGLATRO (5 mg and 15 mg doses), compared with 11.9% (n=327) of patients treated with placebo (HR=0.97; 95.6% CI [0.85-1.11]; p<0.001 for non-inferiority). The key secondary endpoints of superiority for ertugliflozin versus placebo were not met. These key secondary endpoints included: time to the first occurrence of the composite of CV death or hospitalization for heart failure (HHF), time to CV death alone and time to the first occurrence of the composite of renal death, dialysis/transplant or doubling of serum creatinine. The pre-specified endpoint of HHF, while not a part of the hierarchical testing sequence, showed a 30% reduction in the risk of HHF for ertugliflozin versus placebo (2.5% vs. 3.6%; HR=0.70; 95% CI [0.54-0.90]).
“The results of the VERTIS CV trial are a significant and important addition to the overall evidence for the cardiovascular safety profile of ertugliflozin,” said Dr. Sam Engel, associate vice president, Merck clinical research, diabetes and endocrinology.
“We sincerely thank the patients and investigators for their participation in the VERTIS CV study and commitment to the clinical evaluation of ertugliflozin,” said Dr. James Rusnak, senior vice president and chief development officer, internal medicine, Pfizer Global Product Development.
The safety profile of STEGLATRO was consistent with that reported in previous studies.
STEGLATRO is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
The results of VERTIS CV trial were presented today at the American Diabetes Association’s virtual 80th Scientific Sessions.
The VERTIS CV trial is a multicenter, prospective, randomized, event-driven trial in patients with type 2 diabetes and atherosclerotic CV disease. The primary endpoint of the study was non-inferiority on MACE, a composite of CV death, nonfatal myocardial infarction or nonfatal stroke, compared to placebo. The study was designed to evaluate CV safety (non-inferiority) to satisfy the U.S. Food and Drug Administration (FDA) guidance on demonstration of CV safety for novel anti-hyperglycemic agents in the pre-approval and post-approval time periods. The two doses of ertugliflozin were pre-specified to be pooled for assessment of cardiovascular and renal outcomes.
VERTIS CV enrolled 8,246 adults (40 years of age or older) with type 2 diabetes and atherosclerotic CV disease, including patients 65 years of age or older and those with renal impairment or heart failure. More than 99% of patients had established CV disease. Coronary artery disease was reported in 75.9% of patients, cerebrovascular disease in 22.9%, peripheral arterial disease in 18.7%, and history of heart failure in 23.7%. Enrolled patients were randomized to receive ertugliflozin 5 mg (n=2,752), ertugliflozin 15 mg (n=2,747) or placebo (n=2,747) once-daily, added to background standard of care treatment at 531 centers in 34 countries. The mean duration of follow-up was 3.5 years and the mean study drug treatment period was 2.9 years for ertugliflozin and 2.8 years for placebo.
Key secondary endpoints included superiority versus placebo on time to the composite of CV death or HHF, CV death alone and the composite of renal death, dialysis/transplant or doubling of serum creatinine. A hierarchical testing sequence was used across the primary and key secondary hypotheses for the pooled ertugliflozin group versus placebo. Other secondary efficacy outcomes that were not part of the hierarchical statistical testing sequence, but were pre-specified in the protocol, included time to first occurrence of: MACE plus (MACE or hospitalization for unstable angina), fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, individual components of MACE and all-cause death.
Source: Company Press Release