Characterization of telaprevir treatment outcomes and resistance in patients with prior treatment failure: Results from the REALIZE trial


  • Potential conflict of interest: Sandra De Meyer, Inge Dierynck, Anne Ghys, Maria Beumont, Bjorn Daems, and Ben Van Baelen are full-time employees of Janssen Infectious Diseases BVBA. James C. Sullivan, Douglas J Bartels, and Tara L. Kieffer are full-time employees of Vertex Pharmaceuticals. Stefan Zeuzem has been a consultant for Abbott, Anadys, Achillion, Bristol-Myers Squibb, Gilead, Novartis, Merck, Pfizer, Pharmasset, Roche, Vertex Pharmaceuticals, Tibotec Inc., Santaris, and iTherX. Gaston Picchio is a full-time employee of Janssen Research and Development.

  • The clinical trial was sponsored by Janssen Pharmaceuticals and Vertex Pharmaceuticals. Medical writing support and general editorial assistance for this article was provided by Ryan Woodrow and Joanne Williams (Medical Writers, Gardiner-Caldwell Communications, Macclesfield, UK) and funded by Janssen Pharmaceuticals.


In the Phase 3 REALIZE study, 662 genotype 1 hepatitis C virus (HCV)-infected patients with prior peginterferon/ribavirin treatment failure (including relapsers, partial, and null responders) were randomized to 12 weeks of telaprevir given immediately (T12/PR48) or following 4 weeks of peginterferon/ribavirin (lead-in T12/PR48), or 12 weeks of placebo (PR48), combined with a total of 48 weeks of peginterferon alfa-2a/ribavirin. Sustained virologic response (SVR) rates were 64% (T12/PR48), 66% (lead-in T12/PR48), and 17% (PR48). This analysis aimed to characterize treatment outcomes and viral variants emerging in telaprevir-treated patients not achieving SVR. HCV NS3·4A population sequencing was performed at baseline, during treatment, and follow-up. Telaprevir-resistant variants were classified into lower-level (3- to 25-fold 50% inhibitory concentration [IC50] increase: V36A/M, T54A/S, R155I/K/M/T, and A156S) and higher-level (>25-fold IC50 increase: V36M+R155K and A156T/V) resistance. Resistant variants were uncommon at baseline. Overall, 18% (52%, 19%, and 1% of prior null and partial responders and relapsers, respectively) of telaprevir-treated patients had on-treatment virologic failure, with no significant difference with or without a lead-in. Virologic failure during the telaprevir-treatment phase was predominantly associated with higher-level resistance; virologic failure during the peginterferon/ribavirin-treatment phase was associated with higher- or lower-level, or wildtype variants, depending on genotype. Relapse occurred in 9% of patients completing assigned treatment and was generally associated with lower-level resistant variants or wildtype. Resistant variants were no longer detectable by study end (median follow-up of 11 months) in 58% of non-SVR patients. Conclusion: In REALIZE, variants emerging in non-SVR, telaprevir-treated patients were similar irrespective of the use of a lead-in and were consistent with those previously reported. In most patients, resistant variants became undetectable over time. (HEPATOLOGY 2012;56:2106–2115)