Glecaprevir/pibrentasvir

Glecaprevir/pibrentasvir
Combination of
GlecaprevirNS3/NS4A inhibitor
PibrentasvirNS5A inhibitor
Names
Trade namesMavyret, Maviret, others
Clinical data
Main usesHepatitis C.[1][2]
Side effectsHeadache, diarrhea, tiredness[3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1[4]
  • US: N (Not classified yet)[4]
    Routes of
    use    		By mouth (tablets)
    Defined daily dosenot established[5]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa617039
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only) [6]
    • US: ℞-only
    • In general: ℞ (Prescription only)

    Glecaprevir/pibrentasvir (G/P), sold under the brand names Mavyret and Maviret, is a fixed-dose combination medication used to treat hepatitis C.[1][2] It contains glecaprevir and pibrentasvir.[2][7] It works against all six types of hepatitis C.[1] At twelve weeks following treatment between 81% and 100% of people have no evidence of hepatitis C.[3] It is taken once a day by mouth with food.[1][2]

    The most common side effects are headache, diarrhea, and tiredness.[3][8] In those with a history of hepatitis B reactivation may occur.[8] It is not recommended in people with moderate to severe liver disease.[3] Glecaprevir works by blocking the protein NS3/4A protease, while pibrentasvir works by blocking NS5A.[1]

    The combination was approved for medical use in the United States and Europe in 2017.[7][1] It is on the World Health Organization's List of Essential Medicines.[9] In the United States, a course of treatment costs about $27,600 as of 2019.[10] This amount in the United Kingdom costs the NHS about £26,000 as of 2018.[8]

    Medical uses

    In the United States, glecaprevir/pibrentasvir is used to treat adults and children aged 12 years and older or weighing at least 99 pounds with chronic hepatitis C virus (HCV) genotypes 1–6 and both without cirrhosis and with compensated cirrhosis who have not been previously treated for HCV (treatment-naïve).[3][2] It is also used to treat adults and children aged 12 years and older or weighing at least 99 pounds with chronic HCV genotype 1 infection who have previously been treated with a NS5A inhibitor or a NS3/4A inhibitor but not both.[2] The duration of treatment was shortened from 12 weeks to eight weeks for many people in 2019.[3]

    In the European Union, it is used to treat adults and adolescents aged 12 years and older with chronic (long-term) hepatitis C.[1]

    Dosage

    The defined daily dose is not established[5]

    Side effects

    The only known side effects of glecaprevir/pibrentasvir are hepatitis B reactivation, and more commonly headache, nausea, tiredness, and diarrhea.[11]

    Mechanism of action

    Glecaprevir inhibits NS3/4A, a serine protease, and pibrentasvir inhibits NS5A, a zinc-binding hydrophilic phosphoprotein. Both of these proteins are essential in hepatitis C viral RNA replication, which can no longer take place upon inhibition of these proteins.[11]

    History

    The development of glecaprevir/pibrenasvir as a combination treatment was done by AbbVie and is in accordance with good manufacturing practice (GMP) standards, per the FDA.[11]

    Initial identification of glecaprevir was done in a joint effort by AbbVie and Enanta Pharmaceuticals.[12] Enanta had a Collaborative Development and License Agreement with AbbVie for the identification and development of paritaprevir and glecaprevir, two HCV NS3 and NS3/4A protease inhibitors, that lasted from October 2016 to June 2017. In this agreement, Enanta received a total of US$427,000 in the form of license payments, proceeds from a sale of preferred stock, research funding payments, milestone payments, and royalties.[13]

    The identification and development of pibrentasvir was done by AbbVie.[14]

    Society and culture

    Cost

    In the United States, a course of treatment costs about $27,600 as of 2019.[10] This amount in the United Kingdom costs the NHS about £26,000 as of 2018 while in Canada it is CA$40,000.[8][15]

    Research

    During clinical trials, glecaprevir/pibrentasvir was shown to be effective at clearing all six genotypes of HCV from the blood. Over the course of eight studies involving greater than 2,300 patients with hepatitis C, 99% of non-cirrhotic patients with genotype 1 were negative for HCV after the eight-week treatment regimen. Of cirrhotic patients from the same group, 97% tested negative for HCV on a 12-week treatment regimen and the results were reportedly similar for the treatment of genotypes 2 and 4–6, whereas 95% of patients with genotype 3 HCV tested negative for the virus after treatment.[11]

    References

    1. 1 2 3 4 5 6 7 "Maviret EPAR". European Medicines Agency (EMA). 17 August 2017. Archived from the original on 30 December 2019. Retrieved 30 March 2020.
    2. 1 2 3 4 5 6 "Mavyret- glecaprevir and pibrentasvir tablet, film coated". DailyMed. 28 January 2020. Archived from the original on 17 March 2020. Retrieved 30 March 2020.
    3. 1 2 3 4 5 6 "FDA approves treatment for adults and children with all genotypes of hepatitis C and compensated cirrhosis that shortens duration of treatment to eight weeks". U.S. Food and Drug Administration (FDA). 26 September 2019. Archived from the original on 27 September 2019. Retrieved 1 October 2019.
    4. 1 2 "Glecaprevir / pibrentasvir (Mavyret) Use During Pregnancy". Drugs.com. 10 October 2019. Archived from the original on 1 August 2020. Retrieved 30 March 2020.
    5. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 1 July 2021. Retrieved 10 September 2020.
    6. ↑ "Maviret 100 mg/40 mg Film-coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 11 March 2020. Archived from the original on 1 August 2020. Retrieved 30 March 2020.
    7. 1 2 "FDA approves Mavyret for Hepatitis C" (Press release). U.S. Food and Drug Administration (FDA). 3 August 2017. Archived from the original on 30 March 2020. Retrieved 30 March 2020.
    8. 1 2 3 4 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 620. ISBN 9780857113382.
    9. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    10. 1 2 "Mavyret Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 1 August 2020. Retrieved 16 November 2019.
    11. 1 2 3 4 "Drugs@FDA: FDA Approved Drug Products". Food and Drug Administration (FDA). Archived from the original on 1 August 2020. Retrieved 31 October 2017.
    12. ↑ Lawitz, Eric J.; O'Riordan, William D.; Asatryan, Armen; Freilich, Bradley L.; Box, Terry D.; Overcash, J. Scott; Lovell, Sandra; Ng, Teresa I.; Liu, Wei (28 December 2015). "Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection". Antimicrobial Agents and Chemotherapy. 60 (3): 1546–1555. doi:10.1128/AAC.02264-15. ISSN 1098-6596. PMC 4775945. PMID 26711747.
    13. ↑ "enta-10q_20170630.htm". EDGAR. Archived from the original on 7 November 2017. Retrieved 1 November 2017.
    14. ↑ Ng, Teresa I.; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana (May 2017). "In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir". Antimicrobial Agents and Chemotherapy. 61 (5). doi:10.1128/AAC.02558-16. ISSN 1098-6596. PMC 5404558. PMID 28193664.
    15. ↑ "Pharmacoeconomic Review Report: Glecaprevir / Pibrentasvir (Maviret): (AbbVie Corporation): Indication: Hepatitis C genotype 1 to 6 [Internet]". February 2018. PMID 30462452. {{cite journal}}: Cite journal requires |journal= (help)
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