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FDA approves oral interferon-free treatment for genotype 4 HCV infection

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The recent FDA approval of Daklinza and Technivie for hepatitis C offer some additional weapons in the treatment of hepatitis C; however, their approval does not dramatically alter the treatment landscape at this point. Technivie is FDA approved for genotype 4, a small fraction of patients with hepatitis C, and does not offer much improvement over off-label use of Harvoni or Viekira Pak for genotype 4 patients. Daklinza is FDA approved in combination with sofosbuvir for 12 weeks for treatment-naive patients with genotype 3 and should also be considered for off-label use for genotype 2 patients.

While SVRs for noncirrhotic treatment-naive genotype 3 patients are high, achieving high SVRs in patients with cirrhosis requires treatment extension to 24 weeks to achieve an SVR around 90% at a cost of nearly $300,000. While this is an improvement on sofosbuvir plus ribavirin for treatment-experienced patients with cirrhosis, it nevertheless is an extremely expensive option that will likely be met with resistance from payers. It will also likely be displaced as a treatment option for genotype 2 and 3 patients when Gilead's pan-genotypic NS5A inhibitor (GS-5816) makes it to market as anticipated within the next year.

Dr. Sean Koppe is director of hepatology at the University of Illinois Hospital & Health Sciences System, Chicago. He has no conflicts of interest.


 

References

The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.

On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.

Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.

The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.

The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.

The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.

About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.


*This story was updated 7/24/2015.

emechcatie@frontlinemedcom.com

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