EASL 2014 - CARE Liver Disease Faculty. Abstract O8

EASL 2014: Abstract O8. SUCCESSFUL RETREATMENT WITH SOFOSBUVIR-CONTAINING REGIMENS FOR HCV GENOTYPE 2 OR 3 INFECTED PATIENTS WHO FAILED PRIOR SOFOSBUVIR PLUS RIBAVIRIN THERAPY

R. Esteban1, L. Nyberg2, J. Lalezari3, L. Ni4, B. Doehle4, B. Kanwar4, D. Brainard4, M. Subramanian4, W.T. Symonds4, J.G. McHutchison4, M. Rodriquez-Torres5, S. Zeuzem6

1Vall d’Hebron Hospital, Barcelona, Spain, 2Kaiser Permanente, San Diego, 3Quest Clinical Research and University of California-San Francisco, San Francisco, 4Gilead Sciences, Foster City, CA, 5Fundacion de Investigacion, San Juan, PR, United States, 6JW Goethe University Hospital, Frankfurt, Germany

Background and Aims: The efficacy of sofosbuvir (SOF)-containing regimens in patients who failed to achieve sustained virologic response (SVR) with SOF remains unknown. Given the lack of genotypic or phenotypic resistance to SOF in patients who did not achieve an SVR in the Phase 3 program, we designed an open-label study for relapsers to receive either a longer duration of SOF + RBV (24 weeks) or SOF + RBV with peginterferon (PEG-IFN).

Results:

Figure 1. SVR12 by HCV Genotype

Figure 1. SVR12 by HCV Genotype

Conclusions: Retreatment with sofosbuvir regimens of longer duration or with the addition of PEG-IFN in prior SOF failures results in high SVR4 rates and appears to offer a viable approach for GT-2 or GT-3 HCV infected patients who fail to achieve an SVR with SOF+RBV regimens. 

This study includes predominantly genotype 3 persons, with 1/3 with cirrhosis. There are much fewer persons with Genotype 2. The treatment of a genotype 3 person who has failed prior therapy is challenging, especially if there is underlying cirrhosis. At present, the Health Canada approved regimen would be sofosbuvir and ribavirin, the optimal duration likely 24 weeks (based on the VALENCE study). It should be noted that the persons included in this study are prior sofosbuvir + ribavirin failures, as opposed to PEG INF- ribavirin failures. Caution should be exercised as these results are preliminary as the study is ongoing. The regimen of PEG- ribavirin – sofosbuvir appears more efficacious than sofosbuvir-ribavirin for 24 weeks particularly in genotype 3 persons with cirrhosis. The 12 week regimen is approved by Health Canada for genotype 1 patients (NUETRINO Study), and thus safety data is available. This would however be off-label for genotype 2 or 3 persons. The 12-week course would also be cost-saving.

We await with interest the final data particularly as genotype 3 persons are difficult to re-treat.
— CARE Liver Disease Faculty Commentary