Arbutus Biopharma has reported positive preliminary data from a Phase Ia/Ib clinical trial of AB-729 in healthy volunteers and patients with chronic hepatitis B on nucleos(t)ide antiviral treatment.
AB-729 is an RNA interference (RNAi) drug designed to target hepatocytes. The drug was found to block viral replication and decrease all HBV antigens in preclinical models.
The Phase Ia/Ib AB-729-001 study comprises three parts. Part I includes three cohorts of healthy subjects who received 60mg, 180mg or 360mg of AB-729 or placebo.
Part II enrolled non-cirrhotic, HBeAg positive or negative, chronic hepatitis B patients who received 60mg or 180mg of AB-729.
In Part III, chronic hepatitis B subjects will be treated with different AB-729 doses for up to six months.
Safety analysis revealed no serious adverse events, with the majority of mild and unrelated adverse events occurring in healthy participants who received the 60mg, 180mg and 360mg doses.
In HBV patients, HBsAg decrease was found in all subjects in the 180mg cohort. The maximum decline was observed at week four.
The HBsAg decrease in six patients on the 60mg dose was observed at day 29. Participants in this cohort will be followed for 12 weeks.
Arbutus Biopharma chief development officer Dr Gaston Picchio said: “AB-729 dosed at either 60mg or 180mg in chronic hepatitis B subjects was generally safe and well tolerated and resulted in meaningful reductions in HBsAg levels.
“Additionally, after a single 180mg dose, HBsAg levels continued to decline well beyond week 12, suggesting that AB-729 has the potential to be dosed less frequently than every four weeks.”
The company intends to assess the multiple dose portion of the trial with the 60mg dose, along with additional single dose cohorts starting with the 90mg dose.