Glecaprevir/pibrentasvir combo potentially suitable for HCV genotype 5,6
Treatment with the combination of the DAAs* glecaprevir and pibrentasvir led to sustained virological response (SVR) in a majority of patients with chronic hepatitis C virus (HCV) infection genotype 5 or 6, according to the phase IIIB ENDURANCE-5,6** trial.
“These results are consistent with those observed in the glecaprevir/pibrentasvir registrational programme and further strengthen the use of glecaprevir/pibrentasvir in treating patients with chronic HCV genotype 5 and 6 infections,” said the researchers.
This multinational, open-label trial involved 84 treatment-naïve or previously treated adults (54 percent female, 68 percent Asian, 90 percent treatment-naïve) with chronic HCV genotype 5 or 6 infection (HCV RNA ≥1,000 IU/mL; genotype 5: n=23, mean age 68 years; genotype 6: n=61, mean age 54 years) who received once-daily oral doses of glecaprevir/pibrentasvir (300 mg/120 mg). Patients without cirrhosis received treatment for 8 weeks, while those with compensated cirrhosis (11 percent) did so for 12 weeks.
At 12 weeks post-treatment, 97.6 percent of the trial population (n=82) achieved SVR (HCV RNA <15 IU/mL), 95.7 and 98.4 percent with genotype 5 and 6, respectively. [Lancet Gastroenterol Hepatol 2018;doi:10.1016/S2468-1253(18)30341-8]
Fifteen subtypes of genotype 6 were identified in this study, with efficacy achieved in 14 subtypes.
Regarding the two patients who experienced virological failure, one patient with HCV genotype 5a without cirrhosis had achieved SVR at post-treatment week 4 but relapsed at post-treatment week 12, while one patient with HCV genotype 6f with compensated cirrhosis had viral suppression at treatment weeks 4 and 8 but experienced on-treatment virological failure at week 12. Both patients were treatment-naïve at study onset and were adherent to the glecaprevir/pibrentasvir regimen.
A total of 46 adverse events (AEs) were reported, 52 percent of which were mild. The most commonly reported AEs were fatigue and headache (13 percent each). Serious AEs were reported in 6 percent of the patients, though none were considered treatment-related or led to discontinuation, and all patients who experienced serious AEs achieved SVR at 12 weeks post-treatment. There were no incidences of grade ≥3 aminotransferase or total bilirubin concentration elevations.
“[T]he genetic diversity of HCV made the availability of pangenotypic regimens a critical unmet need towards the World Health Organization (WHO) goal of global HCV elimination,” said the researchers, highlighting the particular importance of these regimens in HCV-endemic areas.
“These results support the indication of glecaprevir/pibrentasvir as an 8-week pangenotypic treatment option for patients without cirrhosis and without prior HCV treatment experience, including a 12-week treatment indication for patients with cirrhosis.”
The shorter treatment durations may also help improve adherence and reduce multidrug exposure for patients, they said.
According to Dr Desmond Wai from the Mount Elizabeth Novena Specialist Centre, Singapore, who was not affiliated with the study, this shorter treatment duration is key, particularly in terms of cost-effectiveness.
“In non-cirrhotic patients, just 8 weeks of treatment will do. This will save one-third of the cost of treatment,” he said.
“[Furthermore], glecaprevir/pibrentasvir treats all genotypes so this will help physicians manage HCV patients. Instead of treating different genotypes with or without cirrhosis with different treatments and [for different] durations, we can use just one drug for all types. In the near future, we may not even need to test for genotype before treatment and patients can be safely treated by family physicians [due to the simple] treatment regimen,” said Wai.
DAAs have many potential drug interactions even with common drugs such as statins and proton pump inhibitors, so treating physicians must be aware of these interactions before prescribing these drugs, he added.