ARTICLE | Clinical News

TMC435: Additional Phase IIb data

November 8, 2010 8:00 AM UTC

Additional data from the ongoing, double-blind, placebo-controlled, international Phase IIb PILLAR (TMC435-C205) trial in 386 treatment-naïve patients with chronic HCV genotype 1 infection showed that 79-86% of patients receiving oral TMC435 were able to stop all therapy at week 24 after meeting predefined response criteria of achieving undetectable HCV RNA levels (<25 IU/mL) at week 4 and at weeks 12, 16 and 20. Specifically, the proportion of patients with undetectable HCV RNA levels at week 4 was 77%, 68%, 76% and 79% for the 4 TMC435 regimens - 75 mg TMC435 for 12 weeks, 75 mg TMC435 for 24 weeks, 150 mg TMC435 for 12 weeks and 150 mg TMC435 for 24 weeks -, respectively, vs. 5% for placebo (p<=0.001 for all). At week 12, 91%, 96%, 94% and 97% of patients receiving each respective TMC435 regimen had undetectable HCV RNA levels vs. 58% for placebo (p<=0.001 for all). The viral breakthrough rate was 4.9% for TMC435.

The most common adverse events were headache and fatigue, with no significant differences in the frequency of rash, anemia or gastrointestinal events between treatment groups. Furthermore, significant reductions in alanine and aspartate transaminases were observed in all treatment groups, while small and transient elevations in bilirubin levels were observed in the 150 mg TMC435 arm. Patients received 75 or 150 mg once-daily TMC435 for 12 or 24 weeks in combination with standard of care (SOC; Pegasys peginterferon alfa-2a and Copegus ribavirin) for 24 weeks, or placebo plus SOC for 24 weeks followed by SOC for an additional 24 weeks. TMC435-treated patients who did not meet the predefined stopping criteria at week 24 continued with SOC for an additional 24 weeks. Data were presented at the American Association for the Study of Liver Diseases meeting in Boston. ...