FDA Approves Novel Agent for Treatment of Heart Failure

January 28, 2021
Grace Halsey

The FDA approved vericiguat to reduce the risk of CV death and rehospitalization for HF in HF patients after hospital discharge or after outpatient treatment with IV diuretics.

The US Food and Drug Administration has approved vericiguat (Verquvo; Merck), a novel soluble guanylate cyclase (sGC) stimulator, for reducing the risk of cardiovascular (CV) death and heart failure hospitalization (HHF) following HHF for heart failure (HF) or need for outpatient intravenous diuretics in patients with heart failure and left ventricular ejection fraction (LVEF) <45%.

The approval, announced in a press release from the drug company, is based on results of the phase 3 VICTORIA trial, and makes vericiguat is the first treatment approved specifically for this HF patient population.

“Patients with symptomatic chronic heart failure and reduced ejection fraction have a high risk for hospitalization after experiencing symptoms of heart failure requiring outpatient IV diuretic treatment or hospitalization,” said Paul W. Armstrong, MD, cardiologist and Distinguished University Professor of Medicine at the Canadian VIGOUR Centre, University of Alberta, and study chair of the VICTORIA trial in the Merck release.

“By some estimates, more than half of these patients are rehospitalized within a month of discharge due to a worsening event and approximately one in five die within two years.”

Armstrong notes that the approval is a valuable addition to the current therapies available.

VICTORIA was a phase 3 randomized, parallel-group, placebo-controlled, double-blind, event-driven, multicenter trial and enrolled 5050 patients with New York Heart Association-defined class II, III, or IV chronic HF and LVEF <45% medical centers in 42 countries. Participants were 76% male, 64% Caucasian, 22% Asian, and 5% Black; mean age was 67 years. Patients were randomized to receive vericiguat (n=2526; target dose, 10 mg once daily) or placebo (n=2524), in addition to guideline-recommended medical therapy.

The trial’s primary composite endpoint was death from cardiovascular causes or HHF and median follow-up was 11 months. In a time-to-event analysis, vericiguat was superior to placebo, resulting in a 10% reduction in the primary endpoint HR, 0.90; 95% CI, 0.82-0.98; P=.019).

Early, persistent superiority

The greater efficacy of vericiguat was seen approximately 3 months after treatment began and persisted throughout the trial. The 10% relative difference between groups in the primary composite outcome at a median follow-up of 10.8 months translated into an annualized event-rate reduction of 4.2%; this corresponds with a number needed to treat of 24 patients. This outcome occurred in patients who were receiving guideline-based medical therapy.

According to the Merck press release, adverse events with vericiguat were comparable to placebo; reactions occurring more frequently with vericiguat vs placebo in ≥5% of treated patients included hypotension and anemia. Product labeling, the release advises, includes a boxed warning indicating that vericiguat should not be administered to pregnant women as it may result in fetal harm.