Vericiguat
Clinical data
Trade namesVerquvo
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classSoluble guanylate cyclase activator
ATC code
Legal status
Legal status
Identifiers
  • methyl N-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.247.370
Chemical and physical data
FormulaC19H16F2N8O2
Molar mass426.388 g·mol−1
3D model (JSmol)
  • COC(=O)NC1=C(N=C(N=C1N)C2=NN(C3=C2C=C(C=N3)F)CC4=CC=CC=C4F)N
  • InChI=1S/C19H16F2N8O2/c1-31-19(30)25-14-15(22)26-17(27-16(14)23)13-11-6-10(20)7-24-18(11)29(28-13)8-9-4-2-3-5-12(9)21/h2-7H,8H2,1H3,(H,25,30)(H4,22,23,26,27)
  • Key:QZFHIXARHDBPBY-UHFFFAOYSA-N

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][7] It is taken by mouth.[3][4][7] Vericiguat is a soluble guanylate cyclase (sGC) stimulator.[3]

Common side effects include low blood pressure and low red cell count (anemia).[4][7]

It was approved for medical use in the United States in January 2021,[4][8] and for use in the European Union in July 2021.[7] The U.S. Food and Drug Administration considers it to be a first-in-class medication.[9]

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.[10] 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.[10]

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%.[10] Vericiguat is extensively protein bound in plasma.[10] 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. [10]

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. [11]

Society and culture

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.[12] The applicant for this medicinal product is Bayer AG. Vericiguat was approved for medical use in the European Union in July 2021.[7][13]

References

  1. 1 2 "Verquvo". Therapeutic Goods Administration (TGA). 29 November 2021. Retrieved 28 December 2021.
  2. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
  3. 1 2 3 4 5 6 7 8 "Verquvo- vericiguat tablet, film coated". DailyMed. Retrieved 9 February 2021.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 "Drug Trials Snapshot: Verquvo". U.S. Food and Drug Administration (FDA). 8 February 2021. Retrieved 8 February 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  5. ↑ "Notice: Multiple additions to the Prescription Drug List (PDL) [2023-06-23]". Health Canada. 23 June 2023. Retrieved 3 January 2024.
  6. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  7. 1 2 3 4 5 6 "Verquvo EPAR". European Medicines Agency (EMA). 19 May 2021. Retrieved 14 September 2021.
  8. ↑ "Drug Approval Package: Verquvo". U.S. Food and Drug Administration (FDA). 17 February 2021. Retrieved 14 September 2021.
  9. ↑ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  10. 1 2 3 4 5 "Vericiguat". go.drugbank.com. Retrieved 9 April 2022.
  11. ↑ Hochron, Adam. "FDA Grants Fast Track Designation for Heart Failure Developmental Treatment". www.mdalert.com. Retrieved 9 April 2022.
  12. ↑ "Verquvo: Pending EC decision". European Medicines Agency. 20 May 2021. Archived from the original on 21 July 2021. Retrieved 23 May 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  13. ↑ "Verquvo Product information". Union Register of medicinal products. Retrieved 3 March 2023.

Further reading

  • 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
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