By Gail Connor Roche
Patients with the hepatitis C virus (HCV) who received a 16-week regimen of glecaprevir and pibrentasvir (Mavyret) achieved high sustained virologic response (SVR) rates after previous treatments had failed, new findings show.
An international team of researchers studied 91 individuals with chronic HCV — 87 with genotype 1, and 4 with genotype 4. These patients had prior failures when treated with direct-acting antiviral (DAA) therapies that consisted of at least 1 NS3/4A protease and/or NS5A inhibitor-containing medication.
With glecaprevir and pibrentasvir (G/P), the SVR rate was 89% after 12 weeks and 91% after 16 weeks. The patients received a 3-pill, once-a-day dose of 300 mg/120 mg.
“The few patients who fail a primary treatment attempt with direct acting antivirals have over a 90% chance of cure using a 16-week regimen of the newly approved glecaprevir and pibrentasvir,’’ author Fred Poordad, MD, Professor of Medicine at University of Texas Health, San Antonio, told MD Magazine. “This means we should be able to cure over 99% of all hepatitis C patients.’’
The US Food and Drug Administration (FDA) approved Mavyret on August 3 to treat adults with chronic HCV genotypes 1-6 who have no cirrhosis or mild cirrhosis and may have moderate to severe kidney disease.
Mavyret was also approved for adults with HCV genotype 1 who have undergone therapy with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor.
Previously, patients who experienced virologic failure after therapy that contained an NS5A inhibitor had limited retreatment options, the researchers wrote.
To determine the efficacy and safety of ribavirin (RBV)-free glecaprevir and pibrentasvir in this population, the team looked at individuals who had prior virologic failure on at least one NS3/4A protease and/or NS5A inhibitor-containing therapy.
Poordad explained that individuals who fail to be cured with their first attempt may have baseline resistant variants, which render the medications less effective.
“The combination of glecaprevir and pibrentasvir is a very potent, well tolerated regimen, which covers most of the resistant variants that other regimens cannot cover,” Poordad said. “Hence, failure with other regimens does not mean the patient cannot be cured. This regimen offers another hopeful option.”
Poordad noted that compliance with medications is always critical.
“Patients will fail if they do not comply with the medication regimen,’’ he said.
The researchers reported 1 treatment virologic failure and 4 relapses in the 12-week group. Those treated for 16 weeks had 4 on-treatment virologic failures, the team found.
Prior treatment history with 1 class of inhibitor (protease or NS5A) had no impact on SVR12, while prior treatment with both classes of inhibitors was associated with lower SVR12 rate, they wrote.
The most common adverse event was headache, which was experienced by at least 10% of patients.
“There were no serious adverse events (AEs) assessed as related to study drugs or AEs leading to discontinuation,’’ the researchers wrote.
Poordad said he was not surprised by the findings.
“Based on the in vitro laboratory results of the potency of the G/P regimen, I expected high cure rates in these difficult to cure patients,” he said.
G/P is an excellent option and is less costly than many regimens on the market, Poordad said.
AbbVie sponsored the study, contributed to the collection, analysis, and interpretation of data, and participated in the writing, review, and approval of the manuscript.
The study, “Glecaprevir/Pibrentasvir in Patients with HCV Genotype 1 or 4 and Prior Direct-acting Antiviral Treatment Failure,” was published online in Hepatology last month.