Medical Research: What is the background for this study? What are the main findings?
Dr. Zeuzem: Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C (without and with liver cirrhosis). Among 421 participants, 194 (46%) were women, 157 (37%) were non-white, 382 (91%) had genotype-1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299/316 achieved SVR12 (undetectable HCV 12 weeks after treatment), including 144/157 with genotype-1a, 129/131 with genotype-1b, 18/18 with genotype-4, 8/10 with genotype-6, 68/70 with cirrhosis, and 231/246 without cirrhosis. Virologic failure occurred in 13 patients including 1 breakthrough and 12 relapses, and was associated with baseline NS5A-polymorphisms and emergent NS3- and/or NS5A-variants. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo arms, respectively; none were considered drug-related.
Medical Research: What should clinicians and patients take away from your report?
Dr. Zeuzem: Various interferon-free regimen are available for patients with chronic hepatitis C. Grazoprevir and Elbasvir are co-formulated and will be the second available treatment regimen with a single pill per day. The new treatment is restricted to patients infected with HCV genotypes 1, 4, and 6. In previously untreated patient the addition of ribavirin to this regimen is not required
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Zeuzem: Future research should explore the higher virologic relapse rate in high-viraemic, HCV-1a infected patients with pre-existent resistance-associated variants against elbasvir. The requirement of molecular tests to test for these variants before initiation of theray should be carefully defined.
Stefan Zeuzem, MD; Reem Ghalib, MD; K. Rajender Reddy, MD; Paul J. Pockros, MD; Ziv Ben Ari, MD; Yue Zhao, PhD; Deborah D. Brown, BS; Shuyan Wan, PhD; Mark J. DiNubile, MD; Bach-Yen Nguyen, MD; Michael N. Robertson, MD; Janice Wahl, MD; Eliav Barr, MD; and Joan R. Butterton, MD
MedicalResearch.com Interview with: Stefan Zeuzem, MD (2015). Single Pill Combination Therapy For Some Hepatitis C Subtypes