Drug Combo Promising for HCV Infection in Patients With Advanced CKD
Researchers report a high rate of sustained virologic response after 12 weeks of treatment with a ribavirin-free co-formulation of glecaprevir and pibrentasvir.
Treatment with a ribavirin-free combination of glecaprevir and pibrentasvir is effective for chronic hepatitis C virus (HCV) infection in patients with advanced chronic kidney disease (CKD), a population for which ribavirin-free treatment options are limited, according to investigators.
In the open-label phase 3 EXPEDITION-4 trial, the 104 enrolled patients with stage 4 or 5 CKD and HCV infection treated with a ribavirin-free co-formulation the drugs for 12 weeks had a high rate (98%) of sustained virologic response, Edward Gane, MD, of Auckland City Hospital in Auckland, New Zealand, and colleagues reported in the New England Journal of Medicine (2017;377:1448-1455). In addition, no patients experienced virologic failure during treatment, and none had a virologic relapse after the end of treatment. Adverse events (AEs) reported for at least 10% of patients included pruritus (20%), fatigue (14%), and nausea (12%). Serious AEs were reported for 24% of patients, and 4 patients discontinued the trial treatment because of AEs.
The only current approved treatment regimen for patients who have severe renal impairment and HCV infection is interferon with ribavirin. As the investigators explained, ribavirin accumulates systemically in patients with severe renal impairment, and it is associated with AEs such as hemolytic anemia and pruritus, “thus exacerbating AEs in a population that is already at high risk for anemia and cardiovascular events.”
Of the 104 patients in the trial, 52%, 16%, 11%, 19%, and 2% had HCV genotype 1, 2, 3, 4, and 5 or 6 infection, respectively. Glecaprevir, an NS3/4A protease inhibitor, and pibrentasvir, an NS5A inhibitor, show potent antiviral activity across all 6 major HCV genotypes, the investigators noted.
The trial was funded by AbbVie (ClinicalTrials.gov number NCT02651194).
Gane E, Lawitz E, Pugatch D, et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med 2017;377:1448-1455. doi: 10.1056/NEJMoa1704053