Results from a sub-analysis of the REALIZE phase 3 study showed that Telaprevir, ( Incivo; Incivek ) in combination with Peginterferon alfa and Ribavirin, was associated with cure rates ( defined as a sustained virologic response [ SVR ] ) significantly higher than Peginterferon alfa and Ribavirin alone in patients with genotype-1 chronic HCV and cirrhosis ( 47% vs 10%, respectively ).

Results showed that cirrhotic patients experienced significantly higher cure rates following treatment with a Telaprevir-based regimen compared with Peginterferon alfa and Ribavirin alone. Overall, cirrhotic patients had lower cure rates than those without cirrhosis ( except previous treatment relapsers ), however, treatment with a Telaprevir-based regimen cured nearly half of all patients with cirrhosis.

REALIZE was a randomised, double-blind, placebo-controlled trial to compare the efficacy, safety and tolerability of Telaprevir in 662 patients with chronic genotype-1 HCV who failed prior treatment with Peginterferon alfa and Ribavirin.
Patients received 48 weeks total treatment with Peginterferon alfa and Ribavirin alone or one of two Telaprevir-based regimens ( T/PR ): 12 weeks T/PR plus 36 weeks Peginterferon alfa and Ribavirin alone, or 4 weeks Peginterferon alfa and Ribavirin alone followed by 12 weeks T/PR and 32 weeks Peginterferon alfa and Ribavirin alone.
In this sub-analysis, efficacy and safety variables were reanalysed for 662 patients with and without baseline cirrhosis.

Adverse events were consistent with those reported in the phase 3 studies. Rash, pruritus and anemia ( Hb less than 10 g/dL ) were more frequent in cirrhotic patients receiving Telaprevir ( 42%, 53% and 39% respectively ) than Peginterferon alfa and Ribavirin alone.
Adverse events led to discontinuation of Telaprevir in 15% of cirrhotic and 12% of non-cirrhotic patients.

Telaprevir was approved by the European Commission for the treatment of genotype-1 chronic HCV in previously untreated and treatment-experienced patients in combination with Peginterferon alfa and Ribavirin in September 2011. The approval was based on the results of three phase 3 studies in 2,290 patients: ADVANCE, ILLUMINATE and REALIZE.

Further analysis of the REALIZE study confirms that prior response to treatment may be a more accurate predictor of achieving a cure with Telaprevir than response to a 4 week lead in. Prior relapsers or partial responders who had a poor response after 4-week lead-in phase with Peginterferon alfa and Ribavirin achieved substantially higher cure rates in response to the Telaprevir based regimen than prior null responders, despite similar responses at this time point.

An interim analysis of the EXTEND study highlighted that 99% of patients who achieved a cure after receiving Telaprevir maintained undetectable HCV RNA at a median follow-up of 21 months. One patient had a late relapse 44 weeks after early study dosing discontinuation. Among patients not achieving a cure, variants associated with Telaprevir resistance were no longer observed in 83% of patients at a median follow up of 29 months.

Source: American Association for the Society of Liver Disease ( AASLD ) Annual Meeting, 2011

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