Disappearing Resistance With Telaprevir: The Extend Study

In the Extend study, researchers enrolled volunteers from several previous studies of telaprevir into a multinational three-year study to evaluate the following issues:

• the durability of a sustained virologic response (SVR)
• changes in HCV resistance to telaprevir among people who did not achieve an SVR
• complications

In previous trials researchers detected HCV that was resistant to telaprevir in participants who did not achieve an SVR, specifically in the HCV NS3 protease gene. So research on HCV drug resistance is important in helping researchers understand how best to use telaprevir and other emerging therapies.

Participants in Extend were assessed at the start of the study (baseline) and six months later, and thereafter, once yearly for up to three years in some cases. For the interim analysis reported here, researchers focused on 123 participants who achieved an SVR and 79 others who did not.

Results -- SVR

After an average of two years in Extend, researchers found that SVRs were durable, with 122 out of 123 people (99.2%) continuing to have undetectable HCV. The lower limit of quantification of the assay used was 25 IU/ml.

Among participants with an SVR, no major clinical events occurred.

Results -- No SVR

Among 79 participants who did not have an SVR, 56 had blood samples available for analysis. Here are some of the complications that ensued among participants without an SVR:

• two people developed severe liver complications -- liver cancer in one person with severe pre-existing liver damage and the other person developed HCV-related buildup of waste materials in his blood, which severely affected his brain (HCV encephalopathy).

Initially, various mutations in the HCV protease gene (NS3) were detected in 7% to 45% of people (depending on the mutation). However, after about two years of monitoring, resistant virus could not be found in about 90% of participants.

Reference

1. Zeuzem S, Sulkowski MS, Zoulim F, et al. Long-term follow-up of patients with chronic hepatitis C treated with telaprevir in combination with peginterferon Alfa-2a and ribavirin: interim Analysis of the Extend study. In: Program and abstracts of the 61st Annual Meeting of the American Association for the Study of Liver Diseases, 29 October - 2 November 2010, Boston, MA. Abstract 227.