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Novel Therapeutic Approaches

Current therapies for chronic hepatitis B can suppress HBV replication, but long-term therapy is required in most patients. It is therefore imperative that we continue the search for alternative methods of viral eradication.

HBV core (capsid) protein plays a role in HBV persistence. NVR 3-778 is an HBV core inhibitor that can potentially inhibit viral assembly, HBV genome replication, cccDNA replenishment, and hepatic reinfection cycles.

Yuen and colleagues[18] reported clinical proof-of-concept data from a multicenter phase 1b trial in HBeAg-positive patients randomly assigned to receive NVR 3-778 capsules for 28 days in various doses (100, 200, or 400 mg once daily or 600 mg twice daily). The safety and tolerability of NVR 3-778 were satisfactory for all cohorts, with no treatment-related discontinuations or serious adverse events. Small HBV DNA reductions were apparent following the 200-mg and 400-mg once-daily dose. Of note, tripling of the daily dose to 1200 mg (600 mg twice daily) increased the mean 28-day reduction in serum HBV DNA levels. Pharmacokinetic data indicated multimicromolar concentrations of NVR 3-778 that supported once-daily or twice-daily dosing, with dose-related increases in drug levels.

When used alone or in combination with current HBV antivirals, NVR 3-778 may offer an additive antiviral effect via unique core-related mechanisms and advance clinical care closer to the desired goal of increased durable response rates in patients with chronic hepatitis B.


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