Merck, known as MSD outside the US and Canada, announced results from the phase 3 VICTOR trial evaluating Verquvo (vericiguat) in chronic heart failure with reduced ejection fraction (HFrEF). The study compared Verquvo with placebo in stable patients without recent worsening events, but it failed to meet its primary endpoint.
VICTOR Trial Findings
The trial enrolled 6,105 patients with symptomatic chronic HFrEF (NYHA class II-IV, LVEF ≤40%). These patients had not experienced recent hospitalizations or IV diuretic use. Most were already on guideline-directed medical therapy (GDMT).
- Primary outcome: Cardiovascular death or first hospitalization for heart failure.
- Results: 18% in the Verquvo group vs. 19.1% in placebo (HR 0.93; CI 0.83-1.04; p=0.22).
- Secondary outcomes:
- Cardiovascular death: 9.6% with Verquvo vs. 11.3% with placebo (HR 0.83; CI 0.71-0.97).
- Hospitalization: 11.4% vs. 11.9% (HR 0.95; CI 0.82–1.10). - Safety: Consistent with prior studies.
Nearly half of participants (47.5%) had no prior hospitalizations, making this a relatively stable heart failure population.
Pooled Analysis with VICTORIA
A pre-specified pooled analysis of data from VICTOR and the earlier VICTORIA trial included 11,155 HFrEF patients. Across this broad spectrum, Verquvo showed a statistically significant reduction in the composite endpoint of cardiovascular death or hospitalization.
Dr. Javed Butler, president of the Baylor Scott and White Research Institute, noted that while VICTOR alone missed its target, the pooled data showed clear benefit across disease severity.
Context from VICTORIA
The pivotal VICTORIA trial had focused on high-risk patients with worsening chronic HFrEF and LVEF <45% following a recent event. Verquvo demonstrated reduced risk of death and hospitalization in that population, leading to its approval.
Expert Commentary
Dr. Joerg Koglin of Merck Research Laboratories said VICTOR expands understanding of Verquvo’s role across the spectrum of chronic HFrEF. He reaffirmed confidence in Verquvo’s approved indication for patients with recent worsening events and EF <45%.
Mechanism of Action
Verquvo is an oral once-daily stimulator of soluble guanylate cyclase (sGC), part of the nitric oxide pathway. By raising cGMP levels, it promotes vasodilation, improves vascular tone, and supports cardiac function.
Heart Failure Burden
In the US, 6.2 million adults live with heart failure, with half having HFrEF. About 50% of patients with worsening HFrEF are rehospitalized within 30 days of a worsening event, and one in five die within two years.
Company Collaboration
Since 2014, Bayer and Merck have co-developed vericiguat under a worldwide collaboration on sGC modulators. MSD holds US rights, while Bayer manages commercialization elsewhere.
Takeaway
The VICTOR trial did not confirm benefit in stable HFrEF patients. However, pooled analysis with VICTORIA strengthens evidence that Verquvo reduces cardiovascular death and hospitalizations in a wider patient group. Its role remains solid for patients with recent worsening events, as defined in its FDA-approved indication.
