Glecaprevir-pibrentasvir in HCV Genotypes 1 & 3: SVR Rates High after 8 Weeks

April 12, 2018
Andrew D. Bowser
Andrew D. Bowser

The recently-approved HCV treatment produced SVR rates of 95% or greater and discontinuation rates for AEs were  extremely low.

Patients with hepatitis C virus (HCV) genotype 1 or 3 infection and no cirrhosis had high rates of response with 8 weeks of treatment with glecaprevir plus pibrentasvir, according to recently published results from two pivotal phase 3 trials.

Sustained virologic response (SVR) rates of 95% or greater were reported for treatment groups, and no more than 1% of patients in any group discontinued glecaprevir plus pibrentasvir due to adverse events, according to results reported in the New England Journal of Medicine.

“Patients could benefit from shorter duration treatment options that maintain high efficacy, irrespective of HCV genotype,” wrote first author Stefan Zeuzem, MD, of Goethe University Hospital, Frankfurt, Germany, and co-authors in the report on the studies.

Glecaprevir plus pibrentasvir (Mavyret) is the first-ever HCV therapy approved by the US Food and Drug Administration (FDA) for treatment durations as short as 8 weeks in adult patients without cirrhosis. Previously, standard treatment length was at least 12 weeks.

Reports from other recent phase 3 trials in other HCV genotypes have also shown the efficacy of an 8-week regimen of glecaprevir, a nonstructural protein 3/4A protease inhibitor, coformulated with pibrentasvir, an NS5A inhibitor. In those earlier studies, treatment produced SVR rates of 98% in patients without cirrhosis who have HCV genotype 2 infection, and 93% in patients without cirrhosis who have HCV genotypes 4, 5, or 6.

In the current report, Zeuzem and colleagues described the results of the ENDURANCE-1 and ENDURANCE-3 studies, which included HCV genotype 1 and genotype 3 patients, respectively. Together, HCV genotypes 1 and 3 account for about 70% of HCV infections worldwide.

ENDURANCE-1 included 704 patients with HCV genotype 1 who were randomized 1:1 to receive glecaprevir-pibrentasvir for 8 or 12 weeks. In ENDURANCE-3, 349 patients with HCV genotype 3 were randomized 2:1 to glecaprevir-pibrentasvir or sofosbuvir-daclatasvir for 12 weeks. The ENDURANCE-3 trial also included a third group, including 157 patients who received glecaprevir-pibrentasvir for 8 weeks that was added after data showing the efficacy of the shorter treatment regimen became available.

The primary end point in both studies was rate of SVR at 12 weeks.

Click below for results and discussion

Results

For the genotype 1 patients in ENDURANCE-1, that SVR rate was 99.1% for patients on the shorter 8-week regimen, and 99.7% for patients on the 12-week regimen.

For the genotype 3 patients in ENDURANCE-3, the SVR rate was 95% for 12 weeks of glecaprevir-pibrentasvir, 97% for 12 weeks of sofosbuvir-daclatasvir, and 95% for the added group that received 8 weeks of glecaprevir–pibrentasvir.  results show. Eight weeks of treatment with glecaprevir–pibrentasvir was noninferior to 12 weeks of treatment with that combination.

The rate of serious adverse events was low for glecaprevir-pibrentasvir treatment. according to investigators. There were no grade 3 or greater elevations of alanine aminotransferase levels, and none of the adverse events historically attributed to HCV protease inhibitors, such as rash, anemia, or decreased neutrophil count were observed. 

Taken together, the authors note, the results of these 2 studies suggest that 8 weeks of glecaprevir-pibrentasvir is an “efficacious treatment option” for HCV genotypes 1 and 3.

“Most approved regimens recommend 12 weeks of treatment for patients with HCV infection,” they wrote. “However, patient adherence can decline during the last 4 weeks of treatment, which suggests that shorter treatment durations may improve adherence.”

Source: Zeuzem S, Fosger GR, Wang S, et al. Glecaprevir–pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018; 378:354-369.