Glecaprevir/Pibrentasvir: The First 8-Week, Pangenotypic HCV Treatment Regimen for Patients 12 Years of Age and Older

Abstract

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, dosing, and cost information of glecaprevir/pibrentasvir in the treatment of hepatitis C virus (HCV). Data Sources: A literature search was conducted between September 2018 and July 2019 using PubMed and Google Scholar with the search terms glecaprevir, pibrentasvir, Mavyret, Maviret, and hepatitis C. Clinicaltrials.gov was searched using the same terms. References of published articles were assessed for additional information. Study Selection and Data Extraction: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir were evaluated. Data Synthesis: Food and Drug Administration–approved glecaprevir/pibrentasvir is considered both safe and efficacious for the treatment of HCV genotypes 1 to 6 and in several patient populations, such as those with treatment-naïve or treatment-experienced HCV; with or without compensated cirrhosis, HIV-1 coinfection, or renal impairment; post–liver or post–kidney transplant; and ≥12 years of age. Sustained virological response rates ranged from 83% to 100% in clinical trials, and safety outcomes appear similar to other guideline-recommended HCV treatment options. Relevance to Patient Care and Clinical Practice: This review discusses the pharmacological, efficacy, and safety data found in glecaprevir/pibrentasvir clinical trials and relates this to guideline recommendations and the practical use of this medication for treatment of HCV. Conclusions: With HCV infection rates remaining elevated, it is important to have safe and efficacious treatment options. Glecaprevir/pibrentasvir is a safe and efficacious guideline-recommended, 8-week treatment for HCV in several patient populations, with these populations likely growing in the near future given ongoing and future studies.

Desymmetrization of pibrentasvir for efficient prodrug synthesis

“…1 As the rst pangenotypic 8 week cure for people suffering from HCV, Mavyret® was approved by the U.S. Food and Drug Administration (FDA) in 2017 for the treatment of genotype 1-6 chronic HCV aer a 98% 8 week cure rate was reported for treatment-naive patients without cirrhosis or with compensated cirrhosis. 2 Enabling formulations were required for further improving bioavailability due to challenging physicochemical properties, 3 so a prodrug approach was pursued, resulting in the discovery of phosphates 2, 3, and 4. 4 Pibrentasvir (1, PIB) is a large (MW 1113 g mol À1 ) C 2symmetric drug molecule which presents several uniquely challenging structural features when considering a solubilityenhancing prodrug approach (Fig.…”

Desymmetrization of Pibrentasvir for Efficient Prodrug Synthesis

“…1 As the first pan-genotypic 8-week cure for people suffering from HCV, Mavyret ® was approved by the U.S. Food and Drug Administration (FDA) in 2017 for the treatment of genotype 1-6 chronic HCV after a 98% 8-week cure rate was reported for treatment-naïve patients without cirrhosis or with compensated cirrhosis. 2 Enabling formulations were required for further improving bioavailability due to FIGURE 1. Pibrentasvir (1) structure, challenging features, and PIB prodrugs 2-4 challenging physicochemical properties, 3 so a prodrug approach was pursued, resulting in the discovery of phosphates 2, 3, and 4.…”

Prodrug Strategies to Improve the Solubility of the HCV NS5A Inhibitor Pibrentasvir (ABT-530)

“…Pibrentasvir (ABT-530) is a second-generation HCV inhibitor that targets the NS5A protein, which is used in combination with the HCV NS3 protease inhibitor glecaprevir (ABT-493) for the treatment of HCV genotypes 1–6. − Pibrentasvir (PIB) is a single-digit picomolar inhibitor of wild-type replicons for all major HCV genotypes that maintains potency (less than 10-fold resistance) against variant forms of HCV that are highly resistant to other NS5A inhibitors . Selection experiments in replicon cells for genotypes 1–6 found no significant resistance to PIB .…”