Merck’s Verquvo Fails to Meet Primary Endpoint in Phase III Trial for Chronic Heart Failure and Reduced Ejection Fraction

Results from the Phase III VICTOR trial (NCT05093933) showed that Merck’s Verquvo (vericiguat) failed to meet its primary endpoint in patients with chronic heart failure and reduced ejection fraction (HFrEF). Merck stated that despite the setback, it will continue to support Verquvo’s use within its approved indication while exploring broader insights into the therapy’s potential benefits across the heart failure patient population.¹

What New Insights does VICTOR Offer for Understanding Verquvo in HFrEF?

“By studying patients without recent heart failure hospitalizations, the Phase III VICTOR trial expands our understanding of Verquvo across the full spectrum of chronic heart failure patients with reduced ejection fraction,” said Joerg Koglin, SVP, head, general medicine, global clinical development, Merck Research Laboratories, in a press release. “Together with the previously communicated results in VICTORIA in patients with worsening chronic heart failure and ejection fraction less than 45% following a worsening heart failure event, the results today provide valuable information and add to our understanding of heart failure and Verquvo.

“We are grateful to the patients and investigators for their participation in these studies and remain confident in the role of Verquvo for its approved indication for patients with HFrEF following a recent heart failure event and with ejection fraction less than 45% based on the pivotal Phase III VICTORIA trial.”

VICTOR Trial Design and Patient Population

• The randomized, double-blind, placebo-controlled, multicenter, event-driven VICTOR trial evaluated the safety and efficacy of Verquvo in 6,105 patients with HFrEF and a left ventricular ejection fraction (LVEF) of 40% or less.
• All enrolled patients were required to have not been hospitalized for heart failure within six months or the need for outpatient intravenous diuretics within three months prior to the start of the trial.
• Patients who were already receiving standard guideline-directed medical therapy, including SGLT2 inhibitors and angiotensin receptor-neprilysin inhibitors, were randomly assigned to receive either Verquvo or a placebo.

Endpoints and Results

• The primary endpoint of the trial was the reduction of composite outcome of cardiovascular (CV) death or heart failure hospitalization.
• Key secondary endpoints included time to first occurrence of CV death, time to all-cause mortality, and percentage of patients who experienced one or more serious adverse events (AEs).
• Results showed that 18% of patients in the treatment group experienced a reduced composite outcome of CV death or heart failure hospitalization compared to 19.1% in the placebo group.
• Secondary analyses also suggested numerically lower cardiovascular death (9.6% vs. 11.3%) and similar rates of heart failure hospitalization (11.4% vs. 11.9%) compared to placebo.
• In a pre-specified pooled analysis of VICTOR and the earlier VICTORIA trial—which evaluated patients with worsening HFrEF and ejection fraction <45% following a recent heart failure event—Verquvo demonstrated a statistically significant reduction in CV death or heart failure hospitalization across 11,155 patients.
• The safety profile of Verquvo was found to be consistent with previous studies.^1,2

Expert Perspective

“While the VICTOR trial did not meet its primary endpoint, the separate pooled analysis across both VICTOR and VICTORIA did demonstrate a statistically significant reduction in the primary composite endpoint of heart failure hospitalization and cardiovascular deaths in patients with heart failure and reduced ejection fraction across the disease severity,” said Javed Butler, MD, MPH, MBA, president, Baylor Scott and White Research Institute, professor of medicine, University of Mississippi, in the press release.

References

1. Merck Provides New Results for VERQUVO® (vericiguat) in Patients with Chronic Heart Failure and Reduced Ejection Fraction. Merck. August 30, 2025. Accessed September 2, 2025. https://www.merck.com/news/merck-provides-new-results-for-verquvo-vericiguat-in-patients-with-chronic-heart-failure-and-reduced-ejection-fraction/
2. A Study of Vericiguat (MK-1242) in Participants With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-035) (VICTOR). Clinicaltrials.gov. Accessed September 2, 2025. https://clinicaltrials.gov/study/NCT05093933