In the Journals

Glecaprevir/pibrentasvir safe, effective in cirrhotic patients with HCV

For the treatment of chronic hepatitis C genotype 1 through 6 infections, glecaprevir and pibrentasvir demonstrated safety and efficacy in patients with compensated liver disease, including those with chronic kidney disease stage 4 or 5, according to results pooled from nine phase 2 and 3 trials.

In a related editorial, Jennifer J. Kiser, PharmD, associate professor at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, explained that treating HCV in patients with cirrhosis is a challenge.

“Interferon-free regimens brought tremendous hope for the safe, simple and effective treatment of all individuals with HCV, including cirrhotics,” she wrote. “However, post-market cases of hepatic failure and death with interferon-free therapies containing an HCV protease inhibitor reignited concerns about the safety of HCV treatments in those with cirrhosis.”

Therefore, Edward Gane, MBCHB, MD, FRACP, MNZM, professor of medicine at the University of Auckland, and colleagues conducted an integrated analysis of the safety, efficacy and pharmacokinetics of glecaprevir/pibrentasvir — a pan-genotypic, ribavirin-free, direct-acting antiviral regimen that was approved in 2017 by the FDA. Their analysis included patients with chronic HCV genotype 1 through 6 infections and compensated liver disease, including individuals with chronic kidney disease stage 4 or 5 (CKD 4/5). The patients were part of nine phase 2 and 3 trials that assessed the efficacy and safety of glecaprevir/pibrentasvir treatment for 8 to 16 weeks.

A photo of an infrogrpahic about SVR at 12 weeks in patients taking glecaprevavir/pibrentavir 
 

According to Gane and colleagues, 13% of the 2,369 patients included in the analysis were classified as Child-Pugh Class A. This included 20 patients with CKD 4/5. Less than 1% of patients discontinued the study drug because of adverse events and glecaprevir/pibrentasvir-related serious adverse events. Headache and fatigue were the most common adverse events, and they occurred at similar frequencies in patients with and without cirrhosis. Gane and colleagues discovered that although it was more common to observe serious adverse events among patients with CKD 4/5, they were unrelated to the study drug. Moreover, no cases of drug-induced liver injury or clinically relevant hepatic decompensation were reported.

According to the study, 96.4% of patients with compensated cirrhosis and 97.5% of patients without cirrhosis demonstrated SVR12.

The pharmacokinetics analysis showed a 2.2-fold increase in glecaprevir exposure, but no increase pibrentasvir exposure, in patients with compensated cirrhosis.

In her editorial, Kiser noted that certain patients may be predisposed to higher glecaprevir exposures, which could increase the risk for hepatotoxicity.

“Instruct patients to contact providers if they develop fatigue, weakness, a loss of appetite, nausea and vomiting, yellowing of the eyes or skin, or light-colored stools,” she concluded. - by Marley Ghizzone

Disclosures: Gane reports serving as an advisor for AbbVie, Alnylam, Arbutus, Assembly, Arrowhead, Enanta, Gilead Sciences, Janssen, Merck, Novartis, Novira, Roche and VIR, and participating in speakers’ bureaus for AbbVie and Gilead Sciences. Please see the study and editorial for all other authors’ relevant financial disclosures.

For the treatment of chronic hepatitis C genotype 1 through 6 infections, glecaprevir and pibrentasvir demonstrated safety and efficacy in patients with compensated liver disease, including those with chronic kidney disease stage 4 or 5, according to results pooled from nine phase 2 and 3 trials.

In a related editorial, Jennifer J. Kiser, PharmD, associate professor at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, explained that treating HCV in patients with cirrhosis is a challenge.

“Interferon-free regimens brought tremendous hope for the safe, simple and effective treatment of all individuals with HCV, including cirrhotics,” she wrote. “However, post-market cases of hepatic failure and death with interferon-free therapies containing an HCV protease inhibitor reignited concerns about the safety of HCV treatments in those with cirrhosis.”

Therefore, Edward Gane, MBCHB, MD, FRACP, MNZM, professor of medicine at the University of Auckland, and colleagues conducted an integrated analysis of the safety, efficacy and pharmacokinetics of glecaprevir/pibrentasvir — a pan-genotypic, ribavirin-free, direct-acting antiviral regimen that was approved in 2017 by the FDA. Their analysis included patients with chronic HCV genotype 1 through 6 infections and compensated liver disease, including individuals with chronic kidney disease stage 4 or 5 (CKD 4/5). The patients were part of nine phase 2 and 3 trials that assessed the efficacy and safety of glecaprevir/pibrentasvir treatment for 8 to 16 weeks.

A photo of an infrogrpahic about SVR at 12 weeks in patients taking glecaprevavir/pibrentavir 
 

According to Gane and colleagues, 13% of the 2,369 patients included in the analysis were classified as Child-Pugh Class A. This included 20 patients with CKD 4/5. Less than 1% of patients discontinued the study drug because of adverse events and glecaprevir/pibrentasvir-related serious adverse events. Headache and fatigue were the most common adverse events, and they occurred at similar frequencies in patients with and without cirrhosis. Gane and colleagues discovered that although it was more common to observe serious adverse events among patients with CKD 4/5, they were unrelated to the study drug. Moreover, no cases of drug-induced liver injury or clinically relevant hepatic decompensation were reported.

According to the study, 96.4% of patients with compensated cirrhosis and 97.5% of patients without cirrhosis demonstrated SVR12.

The pharmacokinetics analysis showed a 2.2-fold increase in glecaprevir exposure, but no increase pibrentasvir exposure, in patients with compensated cirrhosis.

In her editorial, Kiser noted that certain patients may be predisposed to higher glecaprevir exposures, which could increase the risk for hepatotoxicity.

PAGE BREAK

“Instruct patients to contact providers if they develop fatigue, weakness, a loss of appetite, nausea and vomiting, yellowing of the eyes or skin, or light-colored stools,” she concluded. - by Marley Ghizzone

Disclosures: Gane reports serving as an advisor for AbbVie, Alnylam, Arbutus, Assembly, Arrowhead, Enanta, Gilead Sciences, Janssen, Merck, Novartis, Novira, Roche and VIR, and participating in speakers’ bureaus for AbbVie and Gilead Sciences. Please see the study and editorial for all other authors’ relevant financial disclosures.