Repeat dosing of targeted interfering RNA shows reduction in HBV burden
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Extending dosing of a novel GalNAc-small interfering RNA brought most patients’ surface antigen levels of hepatitis B virus under control, according to a presenter at the International Liver Congress.
“Repeat dosing of AB-729 [Arbutus Biopharma] ... results in similar mean surface antigen declines with 75% of [patients] achieving surface antigen less than 100 IU/mL,” Man-Fung Yuen, DSc, MD, PhD, chief of the division of gastroenterology and hepatology at the University of Hong Kong, said during his Late Breaker presentation. “These data support the continued evaluation of AB-729 as the cornerstone of combination treatment to achieve functional cure of chronic hepatitis B virus.”
Yuen presented data from part three of the AB-729-001 study in which participants opted into a 6-month extension after their initial 6-month dosing of AB-729 for chronic HBV. Two of the three cohorts analyzed included 60 mg dosing (every 4 weeks, n = 7; every 8 weeks, n = 7) and the third included 90 mg dosing (n = 6). Participants had at least 6 months of stable nucleos(t)ide analogue therapy prior to screening and did not have cirrhosis.
This repeat dosing of AB-729 resulted in comparable HBsAg decline profiles with a plateau around week 20 in each cohort. In both 60-mg groups, five of the seven participants had HBsAg less than 100 IU/mL and five of the six in the 90-mg had the same result.
“The kinetics of surface antigen decline with repeat dosing of 729 were similar across the dosing and dosing intervals assessed today. Notably, there appears to be control of surface antigen response around week 20 despite continued dosing of 729,” Yuen said. “Nevertheless, 15 out of 20 [patients] across the three cohorts achieved surface antigen levels less than 100 IU/mL.”
He showed that in those with quantifiable levels at baseline, modest reductions in hepatitis B core antigen and E antigen were seen, with three of the 12 patients reaching unquantifiable levels.
Yuen also reported that the repeat dosing was safe and well tolerated with no serious adverse events or discontinuation due to adverse events.
“This sustained decline appears to be associated with the immune reawakening in some patients as measured by specific HBV DNA responses and interferon gamma production,” Yuen said.
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Yuen MF. LBO-264. Presented at The International Liver Congress; June 23-26, 2021 (virtual meeting).
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