EASL 2015. Late-breaking Oral 1. The Ruby-I Study

European Association for the Study of the Liver (EASL) 2015

EASL 2015. Late-breaking Oral 1. Safety of Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir for Treating HCV GT1 Infection in Patients with Severe Renal Impairment or End-stage Renal-Disease: The Ruby-I Study. 

P.J. Pockros(1), K R. Reddy(2), P.S. Mantry(3), E. Cohen(4), M. Bennett(5), M.S. Sulkowski(6), D. Bernstein(7), T. Podsadecki(4), D. Cohen(4), N.S. Shulman(4), D. Wang(4), A. Khatri(4), M. Abunimeh(4), E. Lawitz(8).

1. Scripps Clinic, La Jolla, 2. University of Pennsylvania, Philadelphia, 3. The Liver Institute at Methodist Dallas, Dallas, 4. AbbVie Inc., North Chicago, 5. Medical Associates Research Group, San Diego, 6. Johns Hopkins University, Baltimore, 7. North Shore University Hospital, Manhasset, 8. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, United States

Results: 17 (of 20 planned) patients in Cohort 1 received study drug as of 18 Feb 2015; six have completed treatment. 13 of 17 patients reported at least 1 AE, mainly mild or moderate in severity. Two patients experienced serious AEs considered unrelated to DAAs (1 patient: diskitis, respiratory failure. 1 patient: pseudoaneurysm, hemoperitoneum, small bowel obstruction). Both briefly interrupted 3D due to complications of hospitalization; no other patient had an interruption or discontinuation of 3D. Six patients met hemoglobin criteria for interruption of RBV (hemoglobin decrease >2 g/dL during any 4-wk period, or a value <10 g/dL at any time). There was one case of hemoglobin <8 g/dL (hospitalized patient with diskitis). No blood transfusions were performed. All viral loads suppressed rapidly on treatment and there are no cases of virologic rebound or relapse to date.

Conclusions: Among HCV GT1-infected patients with stage 4 or 5 CKD in this ongoing trial, the regimen of 3D±RBV has been well tolerated to date, with no treatment-related serious AEs, one hemoglobin decline to <8 g/dL, and no premature discontinuations of DAAs. All viral loads suppressed rapidly on treatment and there are no virologic failures to date. Available pharmacokinetic and SVR data will be presented.

 

CARE Faculty Perspective:

These preliminary results show promising SVR rates with this combination of agents (ombitasvir/paritaprevir/ritonavir with dasabuvir) in this difficult-to-treat patient population. So far, no patients have experienced virological failures, and preliminary safety reports show patients experience mild-moderate adverse events. Additional Phase 3 studies presented at EASL 2015 on this combination included MALACHITE-I and MALACHITE-II data, and the TOPAZ-I and TOPAZ-II study design.

This combination (ombitasvir/paritaprevir/ritonavir with dasabuvir) was recently approved by Health Canada (December 23, 2014) for the treatment of hepatitis C. It is an all-oral, short- course (~12 weeks), interferon-free treatment, with or without ribavirin (RBV), for the treatment of patients with genotype 1 chronic hepatitis C virus infection, including those with cirrhosis. The approval of this combination was based on a number of trials such as the SAPPHIRE-I and -II trials (EASL 2014) which demonstrated high rates of SVR (96%) for this patient population, as well as PEARL-I and other trials from 2014. 

- CARE Liver Disease Faculty

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