Studies Support Shortened, 8-Week HCV Treatment

Stefan Zeuzem, MD

Evidence supporting the FDA-approved option to shorten treatment of hepatitis C virus (HCV) genotypes 1 and 3 infection without cirrhosis with glecaprevir-pibrentasvir (Mavyret) from 12 weeks to 8 was drawn from two large multicenter trials involving over 1200 patients.

Analysis of data from the phase 3, open-label trials comparing 8 and 12-week regimens was recently consolidated in a report published by Stefan Zeuzem, MD, Professor of Medicine and Chief, Department of Medicine I, Goethe University Hospital, Frankfurt, Germany and colleagues.

"Although the current standard-of-care treatments for patients without cirrhosis who are infected with HCV genotype 1 or genotype 3 result in high rates of sustained virologic response (SVR), patients could benefit from shorter-duration treatment options that maintain high efficacy irrespective of HCV genotype," Zeuzem and colleagues noted.

The ENDURANCE-1 trial evaluated the efficacy and safety of the fixed dose combination of glecaprevir-pibrentasvir (GLE-PIB) in HCV genotype 1-infected patients, including those with human immunodeficiency virus type 1 (HIV-1) co-infection. Patients were randomized in a 1:1 ratio to receive GLE-PIB for either 8 or 12 weeks.

The ENDURANCE-3 trial compared efficacy and safety of GLE-PIB to treatment with sofosbuvir (Sovaldi) dosed with daclatasvir (Daklinza) in treatment-naive patients with genotype 3 infection. Initially, patients were randomized in a 2:1 ratio to receive either GLE-PIB (3 tablets yielding 300mg glecaprevir and 120mg pibrentasvir) or the combination of 400mg of sofosbuvir with 60mg daclatasvir daily for 12 weeks. After the availability of preliminary data supporting the efficacy of an 8-week regimen, the protocol was amended to include a third group for 8 weeks of treatment with GLE-PIB.

"Until recently, there were no approved treatment regimens with a duration of less than 12 weeks for patients with HCV genotype 3 infection," said Zeuzem and colleagues, "and 8-week treatment options for patients with genotype 1 infection were limited according to virus subtype, treatment history, fibrosis stage, or baseline viral load."

Zeuzem and colleagues reported that the SVR at 12 weeks was 99.1% among genotype 1-infected patients receiving 8 weeks of GLE-PIB, compared with 99.7% treated for 12 weeks. In patients with genotype-3 infection treated for 12 weeks, 95% receiving GLE-PIB and 97% receiving sofosbuvir/daclatasvir attained SVR. Ninety-five percent of the patients with genotype 3 infection treated with 8 weeks of GLE-PIB also attained SVR measured at 12 weeks.

Following the ENDURANCE-1 and ENDURANCE-3 trials, there have also been phase 3 trials demonstrating the efficacy of 8-week regimens of GLE-PIB in patients with genotype 2 infection or genotypes 4, 5, or 6, which have yielded SVR rates of 98% and 93%, respectively, according to Zeuzem and colleagues.

"The ability to shorten treatment duration without compromising efficacy remains an important goal in therapy for all HCV genotypes," the investigators indicated.

The report on the comparison of 8-week and 12-week treatment with glecaprevir-pibrentasvir in patients with HCV genotypes 1 or 3 was published in January in The New England Journal of Medicine.