All approved therapy regimens to treat patients with hepatitis C are based on interferon, which must be injected. In this clinical trial to be presented at the annual meeting of the American Association for the Study of Liver Diseases, researchers treated patients - both treatment naive and experienced patients - with a twice daily oral combination therapy of a nucleoside polymerase and protease inhibitor. The results were significant antiviral potency and sustained viral reductions. In addition, the therapy appeared safe and well-tolerated. "The expected better tolerability of these IFN-free combination DAA regimens may make treatment easier for patients and also allow for patients to be treated who are unable to take interferon based therapy," said Edward Gane, MD, lead investigator on this study. "The greater numbers treated and better success rates should eventually help reduce the future projected burden of end-stage liver disease for chronic HCV."
The INFORM-1 trial is randomized, double-blind, and placebo controlled. The oral therapy was administered over a 14-day period, and the antiviral responses were impressive among all groups. It was reported that the combination is undergoing further development for treatment of chronic hepatitis C. "This is the first study to demonstrate that an IFN-free, twice daily, combination DAA regimen produces similar antiviral activity compared to triple therapy (SOC plus protease) over 2 weeks of treatment," said Dr. Gane. "This combination may represent the first IFN-free treatment regimen for both treatment-naive and previously treated patients with HCV Genotype 1 infection."
These results are very promising in regards of antiviral potency and lack of resistance development. "From here we will need to explore in a stepwise fashion if longer treatment will result in persistent viral suppression, clear all HCV-infected hepatocytes and ultimately lead to a sustained virologic response (SVR)," said Dr. Gane. He concluded by saying, "as we explore this new treatment paradigm, we hope to gain a better understanding of the virus host interaction in HCV, as DAA induced viral suppression in the absence of extrinsic interferon allows us to study intrinsic interferon responses and associated biomarkers."
Abstract title:
Combination therapy with a nucleoside polymerase (R7128) and protease (R7227/ITMN-191) inhibitor in HCV: Safety, pharmacokinetics, and virologic results from INFORM-1
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