By Chris Berrie
BERLIN -- April 6, 2011 -- Adding telaprevir to peginterferon alpha-2a plus ribavirin (PegIFN/rbv) demonstrates results that are superior to those with PegIFN/rbv alone in patients with hepatitis C virus genotype 1 (HCV GT1) infection who were prior relapsers, or partial or null responders to PegIFN/rbv treatment, researchers stated here at the 46th Annual Meeting of the European Association of the Study of the Liver (EASL).

The safety profile of the telaprevir (750 mg every 8 hours) plus PegIFN (180 mcg/week)/rbv (1,000-1,200 mg/day) combination in these patients is consistent with that of the treatment of naïve patients, added principal investigator Stefan Zeuzem, MD, PhD, Johann Wolfgang Goethe University Medical Centre, Frankfurt am Main, Germany, speaking here on March 31.

Around 60% of patients with chronic HCV GT1 infection experience treatment failures with standard PegIFN/rbv, requiring further treatment options for these patients.

The so-called REALIZE trial was a multicentre, randomised, double-blind, placebo-controlled trial. "The primary objective," explained Dr. Zeuzem, "was to evaluate the proportion of patients who achieved a sustained virological response, and compare this to the standard of care."

The secondary objectives were to evaluate the PegIFN/rbv lead-in and to assess safety and tolerability.

Subjects were initially stratified according to viral load and previous treatment failure. Randomisation was to standard PegIFN/rbv therapy plus placebo for 16 weeks (PBO/PR48; n = 132), or plus telaprevir for 12 weeks (T12/PR48; n = 266), or plus placebo for 4 weeks lead-in followed by plus telaprevir to 16 weeks (LI-T12/PR48; n = 264). All of these treatments then included standard PegIFN/rbv therapy to 48 weeks, with a further 24 weeks follow-up.

Baseline characteristics were similar across these treatment groups for all 662 subjects.

Sustained virological response for PBO/PR48 (24%) was significantly improved with both T12/PR48 (83%; P <.001) and LI-T12/PR48 (88%; P <.001) for the prior relapsers. Similar, but less beneficial, significant effects were seen in the prior nonresponders (combined partial/null responders; 9% vs 41%, and 41%; P <.001 for both). This last category was also divided into prior partial responders (15% vs 54%, and 59%; P <.001 for both) and prior null responders (5% vs 29%, and 33%; P <.001 for both).

"There was no consistent trend favouring the prior lead-in phase," Dr. Zeuzem noted. Thus the T12/PR48 and LI-T12/PR48 groups were combined to create a new group (T12pool/PR48).

According to HCV subtype (1a and 1b, respectively), in prior relapsers, sustained virological responses for PBO/PR48 (29%, 19%) were again improved for T12pool/PR48 (84%, 88%). Similarly, lower effects were again seen for prior partial responders (19% vs 47%; 10% vs 68%) and prior null responders (6% vs 27%; 5% vs 37%).

Dr Zeuzem also indicated these patterns for sustained virological responses according to baseline fibrosis stage (minimal or portal; bridging; cirrhosis) and prior responses, with cirrhotic patients faring worse in the prior partial and null responders.

Finally, in the safety analysis, looking at discontinuations of either telaprevir or placebo due to any adverse events during the telaprevir treatment phase, these were more frequent in the telaprevir arms: PBO/PR48, 3%; T12/PR48, 15%; LI-T12/PR48, 11%, and mainly seen as rash (0%, 5%, 4%) and anaemia (0%, 2%, 3%). Overall, however, the safety data were comparable with previous telaprevir studies.

Funding for this study was provided by Tibotec Inc.

[Presentation title: REALIZE Trial Final Results: Telaprevir-Based Regimen for Genotype 1 Hepatitis C Virus Infection in Patients With Prior Null Response, Partial Response or Relapse to Peginterferon/Ribavirin. Abstract 5]