By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
The FDA has approved the fourth new product for the treatment of chronic hepatitis C (HCV) infection since November 2013. The latest is a four fixed-drug combination (3-DAA) that includes paritaprevir, a nonstructure 3/4A protease inhibitor, ombitasvir, an inhibitor of the NS5A replication complex, and copackaged with dasabuvir, a nonnucleoside NS5B polymerase inhibitor. The plasma levels of paritaprevir is boosted with ritonavir, a CYP3A inhibitor to permit once-daily dosing. The combination is marketed by AbbVie, Inc. as Viekira Pak.
3-DAA is indicated for the treatment of chronic HCV genotype 1 infections, including patients with compensated cirrhosis.1 Co-administration with ribavirin may be required based on the genotype of the infection and presence of cirrhosis.
The recommended dose is two tablets (ombitasvir, paritaprevir, and ritonavir) once daily in the morning and one tablet of dasabuvir twice daily in the morning and evening. The duration of treatment is 12 weeks for genotype 1a without cirrhosis and genotype 1b with or without cirrhosis. The duration is 24 weeks in patients with genotype 1a with cirrhosis. Co-administration with ribavirin is recommended for genotype 1a patients with and without cirrhosis and genotype 1b patients with cirrhosis. The tablets may be taken without regard to meals.
3-DAA is available as ombitasvir 12.5 mg, paritaprevir 75 mg, and ritonavir 50 mg in one tablet and dasabuvir 250 mg in a separate tablet.
Provides a new effective treatment option for treating HCV.
The presence of ritonavir increases the risks of drug-drug interactions with CYP3A isoenzyme-metabolized drugs. Drugs that are contraindicated with ritonavir include anticonvulsants (carbamazepine), statins (simvastatin), and antimycobacterials (rifampin). Other drugs may be affected to a lesser degree, and may require dose adjustments. The pill burden is slightly higher compared to sofosbuvir/ledipasvir (one tablet daily). The new combination requires ribavirin for genotype 1a and genotype 1b with cirrhosis. The most frequently reported adverse events were fatigue, nausea, pruritus, other skin reactions, insomnia, and asthenia.1
3-DAA was evaluated in six clinical trials.2-6 These include treatment-naïve genotypes 1a infections and 1b without cirrhosis, genotypes 1a and 1b treatment-experienced without cirrhosis, and treatment-experienced and treatment-naïve genotype 1a and 1b with cirrhosis. The primary efficacy endpoint was a sustained virologic response (HCV RNA level < 25 IU/mL) at post-treatment week 12 sustained virological response (SVR12). 3-DAA with ribavirin achieved SVR12 of 96% in treatment-experienced (peginterferon/ribavirin) and treatment-naïve subjects without cirrhosis.2,3 In treatment-naïve subjects, SVR12 was similar with or without ribavirin for genotype 1b (99%) and slightly more effective with ribavirin for 1a (97% vs. 90%).5 In subjects with cirrhosis, 3-DAA with ribavirin achieved SVR12 of 92% for 12 weeks and 93% for 24 weeks of treatment for type genotype 1a in treatment-naïve subjects and 100% for genotype 1b for both durations.6 For those previously treated with peginterferon/ribavirin, SVR12 were 86% and 94% for genotype 1a, and 98% and 100%, respectively. Previous null responders with genotype 1a showed a lower response: 80% for 12 weeks compared to 93% for 24 weeks. For treatment-experienced genotype 1b without cirrhosis, SVR12 without ribavirin was noninferior to treatment with ribavirin.4 In two other studies, 3-DAA achieved SVR12 of 92% in subjects co-infected with HIV-1 and 97% in selected liver transplant subjects.1
The new 3-DAA adds a second interferon-free, 12-week, all oral regimen for the treatment of HCV genotype 1. The SVR12s are very similar to Gilead’s sofosbuvir/ledipasvir (Harvoni) which was approved in October 2014. The current The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommendations lists 3-DAA as alternative to sofosbuvir/ledipasvir for genotypes 1a and 1b (treatment-naïve and peginterferon/ribavirin failures), and genotype 4. This sets up a potential competition between AbbVie and Gilead for this lucrative market. Currently the wholesale cost for 3-DAA is $27,773 for 28 days compared to $31,500 or sofosbuvir/ledipasvir. However with the exception of genotype 1b without cirrhosis, ribavirin is required for 3-DAA at an additional cost of approximately $200 for 28 days. In addition, genotype 1a with cirrhosis requires 24 weeks of treatment compared to 12 weeks for sofosbuvir/ledipasvir.
- Viekira Pak Prescribing Information. AbbVie Inc. December 2014.
- Feld JJ, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014;370:1594-1601.
- Zeuzem S, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014;370:
- Andreone P, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology 2014;147:359-365.
- Ferenci P, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014;370:1983-1992.
- Poordad F, et al. ABT-450/r-ombitasvir and dasabuvir with
ribavirin for hepatitis C with cirrhosis. N Engl J Med 2014;370:
- www.hcvguidelies.org. Accessed 12/30/14.