Telaprevir for Retreatment of HCV Infection

Zeuzem, Stefan M.D.
Andreone, Pietro M.D.
Pol, Stanislas M.D.
Lawitz, Eric M.D.
Diago, Moises M.D.
Roberts, Stuart M.D.
Focaccia, Roberto M.D.
Younossi, Zobair M.D.
Foster, Graham R. F.C.R.P.
Horban, Andrzej M.D.
Ferenci, Peter M.D.
Nevens, Frederik M.D.
Müllhaupt, Beat M.D.
Pockros, Paul M.D.
Terg, Ruben M.D.
Shouval, Daniel M.D.
van Hoek, Bart M.D.
Weiland, Ola M.D.
Van Heeswijk, Rolf Pharm.D.
De Meyer, Sandra Ph.D.
Luo, Don Ph.D.
Boogaerts, Griet M.Sc.
Polo, Ramon Pharm.D.
Picchio, Gaston Ph.D.
Beumont, Maria M.D.

The authors' affiliations are listed in the Appendix.

Address reprint requests to Dr. Zeuzem at the Department of Internal Medicine, Johann Wolfgang Goethe University Hospital, Theodor Stern Kai 7, 60590 Frankfurt, Germany, or at [email protected].

^*The members of the REALIZE study team are listed in the Supplementary Appendix, available at NEJM.org.

Supported by Tibotec and Vertex Pharmaceuticals.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank the members of the data and safety monitoring board: chairperson Francesco Negro, University Hospitals, Geneva; Dominique Larrey, Hôpital Saint Eloi, Montpellier, France; and Tim Friede, University Medical Center, Göttingen, Germany; the study coordinators, nurses, and patients who were involved in the study; and Isabelle Lonjon-Domanec and Ryan Woodrow for their assistance in the preparation of the manuscript.

New England Journal of Medicine 364(25):p 2417-2428, June 23, 2011.

ABSTRACT

BACKGROUND

Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.

METHODS

In this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. The primary end point was the rate of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug.

RESULTS

Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group), a partial response (59%, 54%, and 15%, respectively), and no response (29%, 33%, and 5%, respectively) (P<0.001 for all comparisons). Grade 3 adverse events (mainly anemia, neutropenia, and leukopenia) were more frequent in the telaprevir groups than in the control group (37% vs. 22%).

CONCLUSIONS

Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase. (Funded by Tibotec and Vertex Pharmaceuticals; REALIZE ClinicalTrials.gov number, NCT00703118.)