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EASL 2015: Paritaprevir and Ombitasvir Are Effective for Japanese Patients with HCV Genotype 1b

AbbVie's paritaprevir/ritonavir/ombitasvir coformulation (Viekirax in Europe; part of the Viekira Pak regimen in the U.S.) was highly effective in curing hepatitis C without the accompaniment of dasabuvir (Exviera) in Japanese people with genotype 1b hepatitis C virus (HCV) infection in the GIFT-1 trial, researchers reported at the European Association for the Study of the Liver (EASL) 50th International Liver Congress last week in Vienna.

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Paritaprevir (HCV protease inhibitor) and ombitasvir (NS5A inhibitor) are direct-acting antivirals developed by AbbVie; they are combined in a fixed-dose coformulation with ritonavir, which is used to boost drug levels. Dasabuvir is an HCV polymerase inhibitor. In Europe the paritaprevir/ritonavir/ombitasvir coformulation is sold alone under the brand name Viekirax, while dasabuvir is sold separately as Exviera. In the U.S. they are co-packaged as Viekira Pak. The combination regimen is approved for people with HCV genotype 1. The triple regimen is informally known as "3D" and paritaprevir/ritonavir/ombitasvir without dasabuvir as "2D."

Due to a genetic difference in the way that Japanese people metabolize paritaprevir, the drug has been shown to reach higher levels in the blood when given to these patients, making it possible to administer paritaprevir/ritonavir/ombitasvir without dasabuvir and still achieve a very potent antiviral effect.

The GIFT-1 study was a Phase 3 trial designed to evaluate the safety and efficacy of paritaprevir/ritonavir and ombitasvir, given as a once-daily fixed-dose tablet for 12 weeks, for Japanese people with HCV genotype 1b infection. Genotype 1b is the predominant form of hepatitis C in Japan, accounting for at least 70% of cases. It is easier to treat and less likely to develop resistance than genotype 1a, the most common type in the U.S.

The study enrolled previously untreated and treatment-experienced patients with high baseline viral load (HCV RNA >10,000 IU/mL). The double-blind study randomized 363 people in a 2:1 ratio to receive paritaprevir/ritonavir/ombitasvir (n=215) or placebo (n=106) for 12 weeks. All cirrhotic patients (n=42) received open-label active drug treatment. Participants were stratified by baseline factors that might affect response. 35% of participants in the study were treatment-experienced.

The primary study endpoint was sustained virological response 12 weeks after completion of treatment (SVR12). 95% of participants without cirrhosis and 91% of cirrhotic patients achieved SVR12, and there was no substantive difference in virological response between previously untreated and treatment-experienced patients (94% vs 96%).

Similarly, there was no significant difference in a pre-planned analysis of response according to baseline characteristics. Among the previously untreated group, baseline viral load below 100,000 IU/mL or ineligibility for interferon did not affect response. Among treatment-experienced patients, there was no difference in response according to previous treatment non-response or relapse.

There were 3 on-treatment virological failures and 8 patients experienced viral rebound after completing treatment and before 12 weeks post-treatment, while a further 6 patients were lost to follow up or discontinued treatment due to adverse events, and were also counted as virological failures in the analysis.

Among patients receiving active drug, 9 experienced serious adverse events. The most common adverse events were nasopharyngitis (17%), headache (9%), and peripheral edema (5%).

"High response rates were achieved with the interferon- and ribavirin-free once-daily regimen of [paritaprevir/ritonavir/ombitasvir] in Japanese HCV genotype 1b- infected patients with or without cirrhosis," the researchers concluded. "The 2D regimen was generally well-tolerated with few treatment discontinuations due to treatment-emergent adverse events."

5/1/15

Reference

K Chayama, F Suzuki, K Ikeda, et al. Ombitasvir/paritaprevir/ritonavir for treatment of HCV genotype 1b in Japanese patients with or without cirrhosis: results from GIFT-1. 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract G13.