Treatment with the ribavirin-free combination of glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) for 12 weeks resulted in a sustained virologic response in 98% of patients with both chronic hepatitis C virus (HCV) infection and advanced chronic kidney disease (CKD), according to results of a phase 3 trial published in the New England Journal of Medicine.
Patients with both HCV infection and advanced CKD have very few treatment options. The only currently approved treatment for these patients is interferon with ribavirin. But both interferon and ribavirin have significant side effects. For example, ribavirin can accumulate systemically in patients with severe renal impairment and is associated with adverse events such as hemolytic anemia and pruritus.
As a result, many of these patients remain untreated, the researchers noted.
“Glecaprevir-pibrentasvir may fulfill an important unmet need,” wrote hepatologist Edward Gane, MD, of Auckland City Hospital in Auckland, New Zealand, and colleagues. “The absence of ribavirin as part of the treatment regimen minimizes the risks of treatment discontinuation and of adverse events due to anemia, which represents a considerable benefit for patients with severe renal insufficiency, since they are at increased risk for life-threatening anemia and cardiac events.”
For the multicenter, open-label EXPEDITION-4 trial, researchers in Europe and the US recruited 104 adult patients who had HCV infection (genotypes 1-6) as well as stage 4 or 5 CKD. At baseline, 87% of the patients had stage 5 chronic kidney disease, 82% were undergoing hemodialysis, and 42% had received previous treatment for HCV infection.
For 12 weeks, patients received three co-formulated tablets that comprised a total daily dose of 300 mg of glecaprevir and 120 mg of pibrentasvir. At the end of treatment, 98% of the patients (102 of 104) achieved a sustained virologic response. No patients had virologic failure regardless of HCV genotype, although 2 patients did not have a sustained virologic response at 12 weeks for other reasons.
More than 70% of patients reported at least one adverse event. The most common of these included pruritus (20%), fatigue (14%), and nausea (12%). Serious adverse events occurred in 24% of patients (25 of 104), although none were considered drug-related.
“High rates of serious adverse events are common in this patient population,” the investigators noted.
The rate of adverse events among patients not on hemodialysis was similar to that of patients who were on hemodialysis. “The data from the 19 patients who were not undergoing hemodialysis at baseline suggest that glecaprevir-pibrentasvir did not negatively affect kidney function,” the researchers reported.
They acknowledged that one limitation of the trial was that it included no placebo control group. “The inclusion of a placebo group would have helped clarify the contribution of potential treatment-related adverse events relative to the considerable underlying adverse-event profile observed in HCV-infected patients with advanced renal disease,” they noted.
This trial was funded by AbbVie, manufacturer of the glecaprevir-pibrentasvir combination, Mavyret™.