General Information

Verquvo (vericiguat) is a soluble guanylate cyclase (sGC) stimulator.

Verquvo is specifically indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.

Verquvo is supplied as a tablet for oral administration. The recommended starting dose of Verquvo is 2.5 mg orally once daily with food. Double the dose of Verquvo approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily, as tolerated by the patient. For patients who are unable to swallow whole tablets, Verquvo may be crushed and mixed with water immediately before administration. 

Clinical Trials

The FDA approval of Verquvo was based on the phase 3 VICTORIA trial, a randomized, parallel-group, placebo-controlled, double-blind, event-driven, multi-center clinical trial comparing Verquvo to placebo in 5,050 adult patients with symptomatic chronic heart failure (New York Heart Association [NYHA] class II-IV) and left ventricular ejection fraction (LVEF) less than 45%, following a worsening heart failure event. A worsening heart failure event was defined as heart failure hospitalization within six months or less prior to randomization or use of outpatient IV diuretics for heart failure within three months or less prior to randomization. Patients received up to the target maintenance dose of Verquvo 10 mg once daily or matching placebo. Therapy was initiated at Verquvo 2.5 mg once daily and increased in approximately two-week intervals to 5 mg once daily and then 10 mg once daily, as tolerated. Placebo doses were similarly adjusted. After approximately one year, 90% of patients in both the Verquvo and placebo arms were treated with the 10 mg target maintenance dose. 

In VICTORIA, the primary efficacy objective was to determine whether Verquvo is superior to placebo, both in combination with other heart failure therapies, in reducing the risk of cardiovascular death or heart failure hospitalization in adults with symptomatic chronic heart failure and ejection fraction less than 45% following a worsening heart failure event. Verquvo met the primary efficacy objective based on a time-to-event analysis. Over the course of the study, there was a 4.2% reduction in annualized absolute risk with Verquvo compared with placebo. Therefore, 24 patients would need to be treated over an average of one year to prevent one primary endpoint event.

Side Effects

Adverse effects associated with the use of Verquvo may include, but are not limited to, the following:

• hypotension
• anemia

The Verquvo drug label comes with the following Black Box Warning: EMBRYO-FETAL TOXICITY • Do not administer Verquvo to a pregnant female because it may cause fetal harm. • Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment. 

Mechanism of Action

Verquvo (vericiguat) is a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.

Additional Information

For additional information regarding Verquvo or chronic heart failure, please visit Merck's Verquvo product website.