Triple DAA combo containing ritonavir effective, safe for HCV GT1b in Asians
A combination of the direct-acting antiviral agents (DAAs) ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) and dasabuvir (DSV) resulted in sustained virologic response at post-treatment week 12 (SVR12) in almost all Asian adult patients with genotype 1b (GT1b) chronic hepatitis C virus (HCV) infection without cirrhosis, according to the ONYX-I* study presented at the recent Asian Pacific Association for the Study of the Liver Annual Meeting (APASL 2017) held in Shanghai, China.
“HCV GT1b is the most prevalent subtype in Mainland China, South Korea, and Taiwan,” said Dr Chuang Wan-Long from the Department of Internal Medicine at Kaohsiung Medical University Hospital in Taiwan.
“Interferon (IFN)/pegylated (peg) IFN and ribavirin (RBV) remain the current standard of care in some Asian countries where GT1b has high prevalence,” Chuang said, noting that the practice remained although OBV/PTV/r plus DSV treatment has been shown to achieve 100 percent SVR12 rates in previous phase III studies on GT1b HCV patients with or without compensated cirrhosis, which enrolled mainly non-Asian patients. [Gastroenterology 2014;147:359-365; N Engl J Med 2014;370:1983-1992]
The current double-blind, placebo-controlled, phase III ONYX-I study randomized 650 Asian patients (450 from China, 120 from South Korea, and 120 from Taiwan; 54 percent female) with noncirrhotic GT1b HCV at a 1:1 ratio to receive either OBV/PTV/r+DSV for 12 weeks (Arm A) or placebo for the first 12 weeks followed by another 12 weeks of open-label treatment with OBV/PTV/r+DSV (Arm B). Both treatment-experienced (IFN/pegIFN+RBV) and treatment-naïve patients were included. [APASL 2017, abstract PL005]
In Arm A, all treatment-experienced patients (100 percent) achieved SVR12. Similar results were also seen in treatment-naïve patients, with 183 over 184 patients achieving SVR12 after the OBV/PTV/r+DSV regimen (average 99.5 percent: 99 percent Chinese, 100 percent South Korean, 100 percent Taiwanese).
“One patient in the Chinese cohort of Arm A experienced on-treatment virological failure, [and] pharmacokinetic analysis showed that this patient had concentrations of 0 ng/mL for all components of the triple DAAs regimen at all study visits,” explained Chuang.
Additionally, the combination DAA regimen showed superior SVR12 rate compared with that achieved during the historical telaprevir+pegIFN/RBV, regardless of prior treatment status, according to Chuang.
“The regimen was well tolerated, and adverse events [AEs] were mostly mild in severity,” he added.
During the double-blind period, upper respiratory tract infection (11 percent vs 9 percent in Arms A vs B, respectively), headache (6 percent vs 4 percent), and fatigue (5 percent vs 3 percent) were the most common AEs.
Serious AEs occurred in nine patients during the double-blind period (7 vs 2 in Arms A vs B), but only one case in Arm A was considered as “having a reasonable possibility of being related to the study drug”, who continued treatment and achieved SVR12 eventually.
Abnormal postbaseline laboratory results of grade ≥3 were rare, observed Chuang, adding that “elevations in alanine aminotransferase and bilirubin levels did not associate with each other, or with clinical symptoms, and were all resolved without treatment interruption or discontinuation."
“The efficacy and safety profiles observed in this Asian regional phase III study are similar to those in the Western population,” he concluded.