Positive interim data have been reported for CMX157 (ContraVir Pharmaceuticals), a prodrug of tenofovir, from an ongoing phase 2a multiple-ascending-dose clinical trial. The head-to-head study is directly comparing CMX157 with tenofovir disoproxil fumarate (TDF) (Viread, Gilead) in patients chronically infected with hepatitis B virus (HBV).
The trial is designed to enroll 60 treatment-naïve patients. The sequential dose- escalation format consists of 10 patients per cohort receiving four weeks of a once-daily dose of 5, 10, 25, 50, and 100 mg of CMX157, respectively, plus two patients per cohort receiving 300 mg of TDF, the standard therapeutic dose of Viread.
The patients have successfully completed the 5-mg and 10-mg cohorts. The new interim data were derived from 10 HBV-infected patients who completed 14 days of once-daily oral dosing of 25 mg of CMX157, and two HBV patients treated for 14 days of oral dosing with 300 mg TDF. The CMX157-treated patients showed an average 99% reduction in the HBV viral load compared with baseline. Significantly, the observed antiviral activity for CMX157 was comparable with that observed in TDF-treated patients, but at one-twelfth the dose (25 mg of CMX157 versus the standard 300 mg of TDF).
A key goal of the study was to monitor levels of active tenofovir in the blood. After oral dosing, levels of CMX157 and active tenofovir in the bloodstream were approximately dose-proportional and similar in chronic HBV patients as well as in an earlier study of healthy volunteers. Notably, CMX157 did not appear to break down readily into active tenofovir in the blood (tenofovir: peak concentration = 2.8 ng/mL; area under the curve = 34 ng•h/mL) in contrast to patients taking Viread (tenofovir: peak concentration = 340 ng/mL; area under the curve = 1,910 ng•h/mL). The high levels of circulating tenofovir in subjects taking Viread were consistent with results from earlier clinical studies of the Viread in patients with human immunodeficiency virus or HBV infection.
CMX157 is an analogue of the antiviral drug tenofovir. Its liver-targeting structure results in decreased circulating levels of tenofovir, which reduce systemic exposure and the potential for renal adverse effects. CMX157 previously completed a phase 1b dose-escalation study in healthy volunteers.
Source: ContraVir Pharmaceuticals; October 13, 2016.