Medivir presents OPERA-1 Phase IIa trial data at the AASLD meeting

Nov 4 2009

Data were presented from the phase IIa trial (OPERA-1) for TMC435 at the ongoing 60th annual meeting of the American Association for the Study of Liver Diseases in Boston, USA.

TMC435 is an investigational protease inhibitor, being developed by Tibotec in collaboration with Medivir, for the treatment of hepatitis C virus (HCV).

Data for TMC435 in patients with genotype-1 HCV infection who failed previous IFN-based therapy were presented in a poster titled “Antiviral Activity And Safety Of TMC435 Combined With Pegylated Interferon And Ribavirin In Hepatitis C Patients With Genotype-1 Who Had Previous Exposure To TMC435” by H. Reesink et al.

The data being presented are the week-4 interim results from patients in Cohort 5 of the OPERA-1 (TMC435-C201), a phase IIa study. This is an open-label cohort of five patients who had previous participated in a 5-day phase Ib mono therapy study on TMC435 (TMC435-C101).

Results At week 4, TMC435 given 200 mg once daily, QD, in combination with SoC displayed potent antiviral activity in HCV genotype-1 patients who failed prior IFN-based therapy and had previously been exposed to TMC435. Each of the four patients who completed treatment with TMC435 achieved HCV RNA levels below the lower limit of quantification (25 IU/mL) at Day 28 with three out of four patients having HCV RNA levels below the lower limit of detection (10 IU/mL). No viral breakthroughs were observed to Day 28.

Safety and tolerability The overall safety profile of TMC435 was similar to that having been observed previously; TMC435 is generally safe and well-tolerated. There were no serious adverse events (AEs) and most AEs were mild to moderate in severity and not related to TMC435. The most common AE was influenza-like illness reported in four patients. Four out of five patients completed triple therapy to Day 28, where one patient discontinued treatment after 14 days due to an increase in serum bilirubin (grade 4). This patient already had elevated bilirubin (direct and indirect) levels at study entry. Bilirubin levels decreased after treatment discontinuation and there were no increases in alanine aminotransferase or aspartate aminotransferase.

About TMC435 clinical trial programs The global phase IIb study ASPIRE (TMC435-C205) in genotype 1 HCV treatment- naïve patients have completed enrolment of 400 patients from study sites in North America, Europe and Australia/New Zealand. The primary endpoint is the proportion of patients with undetectable HCV RNA (< 10 IU/mL) 24 weeks after the planned end of treatment (SVR). Patients, in 5 study arms, will receive either 75mg or 150mg of TMC435 or placebo for 12 or 24 weeks.

In the US the second global phase IIb study PILLAR (TMC435-C206) in genotype-1 HCV treatment failure patients have started enrolling patients. The study design is similar to ASPIRE except that there are additional 2 study arms in which patients will receive either 100mg or 150mg TMC435 QD (in combination with SoC) for 48 weeks; the total number of patients to be recruited is 455. In addition a 7-day proof-of-concept monotherapy (phase II) study is ongoing in non genotype-1 treatment-naïve HCV patients (TMC435-C202 or OPERA-2) and furthermore a phase IIb study is ongoing in Japan in treatment naïve genotype-1 HCV patients.