COMMENTARY

New Drug Classes Seek to Further Improve Already Favorable Outcomes in Hepatitis C

William F. Balistreri, MD

Disclosures

January 24, 2017

In This Article

Editor's Note: Several major themes related to hepatitis C virus (HCV) emerged at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases, held November 11-15, 2016, in Boston, Massachusetts. With the success of direct-acting antiviral (DAA) regimens, presentations focused on new drugs and ways to integrate existing and upcoming agents into treatment strategies. In addition, new data on the management of patients with HCV infection during the peri-transplant period, as well as the impact of DAAs on recurrent infection after transplantation, were presented. Of special importance was a discussion on the potential reactivation of hepatitis B virus (HBV) infection during the DAA treatment of HCV infection.

Glecaprevir/Pibrentasvir

The NS3/4A protease inhibitor glecaprevir (GLE; formerly ABT-493) and the NS5A inhibitor pibrentasvir (PIB; formerly ABT-530) are investigational pan-genotypic DAAs with a high barrier to resistance and potent activity against common NS3A and NS5A variants. They are being studied in a coformulated once-daily GLE/PIB regimen (300 mg/120 mg).

The results presented at the meeting confirm the pan-genotypic efficacy of GLE/PIB and demonstrate that this regimen is a suitable option for patients with advanced renal disease.

Noncirrhotic Patients with Chronic HCV Genotypes 1 to 6 Infection

Zeuzem and colleagues evaluated the safety and efficacy of treatment with GLE/PIB in 703 patients with chronic genotype 1 HCV infection without cirrhosis.[1] The investigators found that an 8-week treatment course was noninferior to a 12-week course. Sustained virologic response at 12 weeks (SVR12) was above 99% in treatment-naive patients and in interferon/ribavirin (RBV) and/or sofosbuvir (SOF)-experienced patients.

Similarly, Hassanein and colleagues reported that 8 weeks of treatment with GLE/PIB yielded an overall response rate of 98% in noncirrhotic patients with genotype 2, 4, 5, or 6 infections, regardless of baseline polymorphisms or previous treatment experience.[2]

Chronic HCV Genotype 1 to 6 Infection and Renal Impairment

Because neither GLE nor PIB undergoes significant renal excretion, these agents are potentially suitable treatment options for HCV- infected patients with renal disease. In fact, pharmacokinetic studies have shown that patients with renal disease experience no more clinically relevant increased exposure to GLE/PIB than patients with normal renal function.

In a follow-up study, Gane and colleagues assessed the safety and efficacy of 12 weeks of GLE/PIB for patients infected with genotypes 1 to 6 HCV and severe renal impairment.[3] The drugs were equally successful against all six HCV genotypes, regardless of treatment history, with 98% of patients achieving SVR12. The fixed-dose combination of GLE/PIB was well tolerated; serious adverse events were considered unrelated to the study drugs.

HCV Genotype 3 Infection With Previous Treatment Experience and/or Cirrhosis

Wyles and colleagues reported the efficacy and safety of GLE/PIB in patients with chronic genotype 3 HCV infection.[4] They found that in noncirrhotic, treatment-experienced patients, virologic response rates were higher with 16 weeks of treatment than with 12 weeks of treatment (96% vs 91%). In treatment-naive cirrhotic patients, SVR12 rates were 98% after 12 weeks of therapy and 96% after 16 weeks of therapy. Treatment was generally well tolerated, and no patient discontinued the drugs because of adverse events.

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