First Hepatitis B Patients Treated in Study of New Therapy at Lower Doses Than Standard

First Hepatitis B Patients Treated in Study of New Therapy at Lower Doses Than Standard

ContraVir Pharmaceuticals announced the dosing of the first patients with chronic hepatitis B enrolled in its head-to-head Phase 2a clinical trial comparing multiple doses of the company’s lead candidate CMX157 to tenofovir disoproxil fumarate (TDF), a standard therapy. Specifically, the trial will compare a lower dose of CMX157 to the commonly used dose of TDF (Viread, Gilead Sciences).

CMX157 is a novel lipid acyclic nucleoside phosphonate that delivers high intracellular concentrations of the active antiviral agent tenofovir. The trial will evaluate the potential for CMX157, which the company considers more potent than TDF, to be more effective at lower dose levels, decreasing the circulating levels of tenofovir, lowering systemic exposure, and so reducing the renal side effects associated with the drug. ContraVir plans to conclude the trial, taking place in Thailand, toward the year’s end.

A sequential dose escalation safety and tolerability study, the trial (NCT02710604) will enroll 60 treatment-naïve patients chronically infected with hepatitis B virus (HBV). Ten patients per cohort will be given a once-daily dose of either 5, 10, 25, 50 or 100 mg of CMX157 for 28 days, and two patients per cohort will receive 300 mg of TDF, the standard dose for Viread, for 28 days.

CMX157 has completed a Phase 1 clinical trial in healthy volunteers demonstrating a favorable safety, tolerability, and drug distribution profile.

“This marks the first time CMX157 will be dosed in HBV patients,” said James Sapirstein, CEO of ContraVir, in a press release. “We anticipate that this study will reflect the positive findings from our animal and in vitro studies, which demonstrated superior potency against HBV and significant liver targeting, allowing the potential for CMX157 to reduce the risk of kidney and bone toxicities by being more effective at lower doses.

“We expect the current study will validate CMX157’s potential to be dosed lower than Viread, and at the same or lower dose than Gilead’s tenofovir alafenamide, or TAF,” he said. “In addition, we’re happy to report that the Phase 1b study continues to advance smoothly and in line with our expectations into the final 100 mg dosing group, without any safety or tolerability concerns.”

An estimated 240 million people are chronically infected with HBV (defined as hepatitis B surface antigen positive for at least 6 months). More than 780,000 die every year due to HBV complications, including cirrhosis and liver cancer. The primary goal in chronic hepatitis B treatment is to suppress HBV replication and induce liver disease remission prior to the onset of complications.

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