What is the role of MAVYRET (glecaprevir/pibrentasvir) in the treatment of Hepatitis C?

From the Guidelines

MAVYRET (glecaprevir/pibrentasvir) is a highly effective treatment for hepatitis C virus (HCV) infection, with a standard regimen of one dose daily (three tablets taken at once with food) for 8 weeks in most treatment-naïve patients without cirrhosis or with compensated cirrhosis. For patients who have been previously treated or have specific genotypes with cirrhosis, a 12 or 16-week course may be required. The treatment works by directly targeting the virus through two mechanisms: glecaprevir inhibits the NS3/4A protease while pibrentasvir blocks the NS5A protein, both essential for viral replication. This dual-action approach leads to cure rates exceeding 95% across all six major HCV genotypes, as supported by studies such as the one published in the Journal of Hepatology in 2020 1. Before starting treatment, patients should be tested for hepatitis B as MAVYRET can reactivate this virus. Common side effects include headache, fatigue, and nausea. MAVYRET should not be used in patients with moderate to severe liver impairment (Child-Pugh B or C) or those taking atazanavir or rifampin. Regular monitoring of liver function during treatment is recommended, and patients should avoid alcohol to prevent further liver damage while undergoing therapy. Key considerations for treatment include the patient's genotype, presence of cirrhosis, and prior treatment experience, as outlined in guidelines such as those from the European Association for the Study of the Liver (EASL) 1. In patients with renal impairment, including those on haemodialysis, MAVYRET has been shown to be effective and safe, with no dose adjustments necessary, as demonstrated in studies like the EXPEDITION-4 trial 1. Overall, MAVYRET offers a highly effective and well-tolerated treatment option for HCV infection, with the potential to cure the disease in the majority of patients.

Some key points to consider when treating HCV with MAVYRET include:

• The importance of testing for hepatitis B before starting treatment
• The need for regular monitoring of liver function during treatment
• The potential for drug interactions, particularly with atazanavir or rifampin
• The effectiveness and safety of MAVYRET in patients with renal impairment, including those on haemodialysis
• The high cure rates achievable with MAVYRET across all six major HCV genotypes, as supported by studies such as those published in the Journal of Hepatology in 2020 1 and the Clinical and Molecular Hepatology in 2018 1.

From the FDA Drug Label

MAVYRET is a fixed-dose combination of glecaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor, and is indicated for the treatment of adult and pediatric patients 3 years and older with chronic HCV genotype (GT) 1,2,3,4,5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both.

MAVYRET is indicated for the treatment of hepatitis C in adult and pediatric patients 3 years and older with:

• Chronic HCV genotype 1,2,3,4,5, or 6 infection without cirrhosis or with compensated cirrhosis
• HCV genotype 1 infection who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both 2

From the Research

Efficacy of MAVYRET (Glecaprevir/Pibrentasvir) for Hepatitis C Treatment

• The overall sustained virological response rate at 12 weeks post-treatment (SVR12) for glecaprevir/pibrentasvir was 97.8% in a systematic review and meta-analysis of 13 studies with 3082 patients 3.
• High SVR12 rates were achieved across different HCV genotypes, including genotype 1 (99.8%), genotype 2 (99.2%), genotype 3 (96.1%), and genotype 4-6 (100%) 3.
• The treatment was also effective in patients with compensated cirrhosis, with an SVR12 rate of 98.8% 3.
• A prospective multicenter study found that the overall SVR12 rate for glecaprevir/pibrentasvir was 99.1% in 1439 patients, with high SVR12 rates achieved in patients with genotype 1 (99.4%) and genotype 2 (99.4%) 4.

Safety Profile of MAVYRET (Glecaprevir/Pibrentasvir)

• Virological failure and relapse, as well as serious drug-related adverse events, were rare in patients treated with glecaprevir/pibrentasvir 3.
• Adverse events were reported in 28.2% of patients in a prospective multicenter study, with 1.6% of patients discontinuing treatment due to drug-related adverse events 4.
• The treatment was well-tolerated in patients with severe chronic kidney disease, including those undergoing hemodialysis 5.

Special Populations and Retreatment

• Glecaprevir/pibrentasvir can be safely used in patients with severe chronic kidney disease, including those undergoing hemodialysis 5.
• Patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be closely observed due to a higher risk of non-SVR12 4.
• A case report found that sofosbuvir/velpatasvir plus ribavirin combination therapy was effective for retreatment of HCV after failure of glecaprevir/pibrentasvir therapy 6.