Medicine - Xagena

A Phase Ib clinical trial showed that the oral hepatitis C virus ( HCV ) protease inhibitor, VX-950, for 5 and 14 days was well-tolerated in both healthy volunteers and in patients with chronic HCV infection.

In addition, patients treated with 750 mg of VX-950 every eight hours achieved a median reduction of HCV-RNA of 4.4 log10, equivalent to a 25,000-fold reduction in viral levels, at the end of 14 days of treatment.

At the end of 14 days of treatment, 4 of 8 patients in the 750 mg dose group tested HCV-RNA negative in the quantitative Roche COBAS TaqMan assay ( <30 IU/mL ); 2 of these 4 patients tested undetectable in the qualitative Roche TaqMan assay ( limit of detection 10 IU/mL ).
A patient in another VX-950 dose group also achieved plasma HCV-RNA below the limit of quantitation by the end of treatment.

All patients in the clinical trial had genotype 1 HCV infection, the most difficult strain to treat, and were either non-responsive to prior treatment or treatment-naïve.

“ Preliminary results from this early Phase Ib clinical study suggest that the investigational drug VX-950 produces a rapid and profound reduction in HCV-RNA as a single agent,” said Henk W. Reesink, at Academic Medical Center in Amsterdam.. “ In the best dose group in the Phase Ib clinical study, VX-950 reduced HCV viral load in some patients to below the limit of detection of the most sensitive assays in two weeks. VX-950 was also well-tolerated in this study. These data further support the view that HCV protease is the most potent single mechanism for suppressing hepatitis C viral replication.”

VX-950 is an oral inhibitor of hepatitis C virus protease, an enzyme essential for viral replication. Vertex completed a Phase Ia clinical study of VX-950 in healthy volunteers in 2004, which indicated that VX-950 was well-tolerated in ascending single doses up to 1250 mg.
Pharmacokinetic results from the Phase Ia study suggested that VX-950 can achieve liver concentrations substantially greater than IC50 and IC90 observed in non-clinical studies.
Preclinical studies, presented at various medical conferences in 2003 and 2004, demonstrated that VX-950 significantly reduces levels of HCV RNA in both an in vitro replicon system and infectious virus assays.

Source: Digestive Disease Week, 2005


XagenaMedicine2005