Vericiguat

Pregnancy
categoryRoutes of
administrationBy mouthDrug classSoluble guanylate cyclase activatorATC codeLegal statusLegal status IdentifiersCAS NumberPubChem CIDDrugBankChemSpiderUNIIKEGGChEBIChEMBLCompTox Dashboard (EPA)ECHA InfoCard100.247.370 Chemical and physical dataFormulaC₁₉H₁₆F₂N₈O₂Molar mass426.388 g·mol⁻¹3D model (JSmol)

Vericiguat, sold under the brand name Verquvo, is a medication used to reduce the risk of cardiovascular death and hospitalization in certain patients with heart failure after a recent acute decompensation event.^[3][4][8] It is taken by mouth.^[3][4][8] Vericiguat is a soluble guanylate cyclase (sGC) stimulator.^[3]

Common side effects include low blood pressure and low red cell count (anemia).^[4][8]

It was approved for medical use in the United States in January 2021,^[4][9] and for use in the European Union in July 2021.^[8] The U.S. Food and Drug Administration considers it to be a first-in-class medication.^[10]

Medical uses

Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure following a prior hospitalization for heart failure or need for outpatient intravenous diuretics, in adults with symptomatic chronic heart failure and an ejection fraction of less than 45%.^[3][4]

Adverse effects

Vericiguat causes harm to the unborn baby and should not be given to pregnant women.^[4] It is not known to what extent vericiguat passes into breastmilk; therefore, breastfeeding patients should not take vericiguat.

The most common side effects of vericiguat include low blood pressure and anemia.^[3] Patients taking other soluble guanylate cyclase inhibitors should not take vericiguat.^[3]

Pharmacology

Vericiguat is a direct stimulator of soluble guanylate cyclase, an important enzyme in vascular smooth muscle cells. Specifically, vericiguat binds to the beta-subunit of the target site on the soluble guanylate cyclase enzyme.^[11] Soluble guanylate cyclase catalyzes the formation of cyclic GMP upon interaction with nitric oxide to activate a number of downstream signaling cascades, which can compensate for defects in this pathway and resulting losses in regulatory myocardial and vascular cellular processes due to cardiovascular complications.^{[11][vague][clarification needed]}

Pharmacokinetics

After vericiguat is administered (100 mg by mouth once daily), the average steady state and Cmax and AUC for patients with cardiovascular failure is 350 mcg/L and 6,680 mcg/h/L with a Tmax of one hour. Vericiguat has a positive food effect, and therefore patients are advised to consume food with the drug for an oral bioavailability of 93%.^[11] Vericiguat is extensively protein bound in plasma.^[11] Vericiguat is primarily metabolized via phase 2 conjugation reactions, with a minor CYP-mediated oxidative metabolite. The major metabolite is glucuronidated and inactive. The typical half-life profile for patients with heart failure is 30 hours. Vericiguat has a decreased clearance in patients with systolic heart failure. ^[11]

History

The U.S. Food and Drug Administration (FDA) approved vericiguat based on evidence from a clinical trial (NCT02861534) which consisted of 5,050 participants aged 23 to 98 years old with worsening heart failure.^[4] The trial was conducted at 694 sites in 42 countries in Europe, Asia, North and South America.^[4] The trial enrolled participants with symptoms of worsening heart failure.^[4] Participants were randomly assigned to receive vericiguat or a placebo pill once a day.^[4] Neither the participants nor the health care professionals knew if the participants were given vericiguat or placebo pill until after the trial was complete.^[4] It was awarded a fast track designation on 19 January 2021. ^[12]

Society and culture

Legal status

On 20 May 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for vericiguat, intended for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction.^[13] The applicant for this medicinal product is Bayer AG. Vericiguat was approved for medical use in the European Union in July 2021.^[8][14]

References

Further reading

• Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, et al. (May 2020). "Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction". N Engl J Med. 382 (20): 1883–1893. doi:10.1056/NEJMoa1915928. PMID 32222134.

External links

• Clinical trial number NCT02861534 for "A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001) (VICTORIA)" at ClinicalTrials.gov