Merck & Co. and Bayer’s Verquvo failed to deliver a composite cardiovascular benefit for certain patients with stable heart failure with reduced ejection fraction (HFrEF).
The phase 3 Victor trial failed on its primary endpoint, as Verquvo didn’t beat placebo in terms of combined time to first heart failure hospitalization or cardiovascular death, according to results presented at the European Society of Cardiology Congress 2025.
The study evaluated Verquvo in more than 6,100 well-managed HFrEF patients who had not had a heart failure hospitalization within six months or the need for outpatient intravenous diuretics within three months prior to the study. About 47.5% of patients had no history of hospitalization for heart failure.
The readout was perplexing because investigators observed seemingly divergent results on the two components that formed the trial’s primary composite endpoint.
Verquvo led to a numerical 17% reduction in the risk of heart-related death. The number did not bear statistical significance because secondary endpoints were not formally tested thanks to the trial’s failure on its primary endpoint.
Death from cardiovascular causes occurred in 292 (9.6%) patients in the Verquvo arm and 346 (11.3%) in the control group after a median follow-up of 19.7 months, according to results simultaneously published in The Lancet.
In contrast, the drug showed no sign of benefit on time to first heart failure hospitalization, with Verquvor’s 11.4% first-time hospitalization rate during the study timeframe looking similar to placebo’s 11.9%. When first and recurrent hospitalizations were counted, Verquvo’s rate was 10.7 events per 100 patient-years versus 11.8 events per 100 patient-years for the placebo cohort.
“Cardiovascular death is a clinically meaningful and less ambiguous endpoint than outcomes such as hospitalization, which can be influenced by clinical practice and regional variation,” the Victor trial’s investigators wrote in The Lancet paper.
Trying to reconcile the difference between the two endpoints, the researchers pointed to “the unprecedented high use of guideline-directed medical therapy,” such as SGLT2 inhibitors, in a population with overall low risk at baseline.
Even though the researchers hypothesized that the high use of contemporary therapy and low recent hospitalization rates could offer plausible explanations for the lack of a hospitalization benefit, they acknowledged that “[t]he reason for the observed mortality benefit in the absence of a reduction in heart failure hospitalization is unclear.”
All told, on the composite endpoint, Verquvo only led to a nonsignificant 7% reduction in the risk of cardiovascular death or first hospitalization for heart failure during a median follow-up of 18.5 months.
Verquvo received its initial FDA approval in HFrEF in 2021 based on results from the phase 3 Victoria trial. The study linked the soluble guanylate cyclase stimulator to a reduced risk of cardiovascular death and heart failure hospitalization versus placebo among patients with worsening disease.
At ESC, Merck also trotted out a pooled analysis of Victor and Victoria, showing that Verquvo significantly reduced patients’ risk of cardiovascular mortality or heart failure hospitalization by 9% versus placebo. The risk reduction was 11% and 8% for the marker’s two components, respectively.
Through a collaboration formed in 2014, Merck markets Verquvo in the U.S. and Bayer commercializes it in the rest of the world.
Analysts don't hold big expectations for Verquvo because of competition in the heart failure field. At the time of the drug’s approval in 2021, Leerink Partners analysts projected its U.S. peak sales would reach $300 million based on some use in HFrEF patients who are not optimally managed on Novartis’ Entresto.
In the first half of 2025, Merck only recorded $21 million in sales from the med in the U.S.