vericiguat

Common name: vericiguat

Trade name: Verquvo

All names: vericiguat, Verquvo, vericiguat

Indications:

VERQUVO is a soluble guanylate cyclase (sGC) stimulator that reduces the risk of cardiovascular death and hospitalization for heart failure (HF) due to or requiring treatment as an outpatient intravenous diuretic in less than 45% of adults with symptomatic chronic heart failure.

Usage and Dosage:

The recommended starting dose of VERQUVO is 2.5 mg taken orally daily with food.

Double the VERQUVO dose approximately every 2 weeks to achieve the patient-allowed target maintenance dose of 10 mg per day.

For patients who have difficulty swallowing, the tablets may be crushed and mixed with water.

Specifications:

2.5mg; 5 mg; 10mg

Adverse reactions:

The most common adverse reactions of ≥5% are hypotension and anemia.

Contraindications:

Patients taking other soluble guanylate cyclase (sGC) stimulators concurrently.

Pregnancy

Precautions:

Do not give VERQUVO to pregnant women as it may cause fetal harm.

Females of reproductive potential: Pregnancy should be ruled out before initiating treatment. To prevent pregnancy, females of reproductive potential must use effective contraception during treatment and for one month after discontinuation of treatment.

PDE-5 inhibitors: simultaneous use is not recommended.

Lactation period: Breastfeeding is not recommended.

Storage:

At 20°C to 25°C (68°F to 77°F); allowed excursion range is 15°C to 30°C (between 59°F and 86°F).

Mechanism of action:

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 intracellular synthesis of cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in regulating vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of vitamin C and reduced activity of NO and sGC, which may lead to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, vericiguat increases intracellular cGMP levels, leading to smooth muscle relaxation and vasodilation.

Safety and efficacy:

Verquvo (vericiguat) is the first new drug approved by the US FDA in 2021 and the first soluble guanylate cyclase (sGC) agonist to treat patients with worsening chronic heart failure. It is the first chronic heart failure treatment approved for patients who are hospitalized for heart failure or require IV diuretics and is based on results from the pivotal Phase 3 VICTORIA trial and follows a priority regulatory review.

This approval is supported by results from a Phase 3 clinical trial called VICTORIA. The trial is specifically targeting people with exacerbation of chronic heart failure who are at high risk of cardiovascular death and who have had recurrent heart failure hospitalizations. Data from VICTORIA have been published in the New England Journal of Medicine. The results at a median follow-up period of 10.8 months showed that the Verquvo treatment group reduced the risk of patients' composite end point of hospitalization for heart failure and death from cardiovascular causes compared with the placebo group (35.5% vs 38.5%, HR=0.90, P=0.02).