Safety, pharmacokinetics, and antiviral activity of the capsid inhibitor AB-506 from Phase 1 studies in healthy subjects and those with hepatitis B
Issued Date
2022-12-01
Resource Type
eISSN
2471254X
Scopus ID
2-s2.0-85139171097
Pubmed ID
36194181
Journal Title
Hepatology Communications
Volume
6
Issue
12
Start Page
3457
End Page
3472
Rights Holder(s)
SCOPUS
Bibliographic Citation
Hepatology Communications Vol.6 No.12 (2022) , 3457-3472
Suggested Citation
Yuen M.F., Berliba E., Sukeepaisarnjaroen W., Ahn S.H., Tanwandee T., Lim Y.S., Kim Y.J., Poovorawan K., Tangkijvanich P., Schwabe C., Eley T., Brown J., Lee A.C.H., Thi E.P., Paratala B., Mani N., Sofia M.J., Picchio G., Sims K.D., Gane E.J. Safety, pharmacokinetics, and antiviral activity of the capsid inhibitor AB-506 from Phase 1 studies in healthy subjects and those with hepatitis B. Hepatology Communications Vol.6 No.12 (2022) , 3457-3472. 3472. doi:10.1002/hep4.2095 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85249
Title
Safety, pharmacokinetics, and antiviral activity of the capsid inhibitor AB-506 from Phase 1 studies in healthy subjects and those with hepatitis B
Author's Affiliation
Siriraj Hospital
Severance Hospital
Asan Medical Center
Chulalongkorn University
Seoul National University Hospital
Hospital for Tropical Diseases, Bangkok
Khon Kaen University
The University of Hong Kong
The University of Auckland
Discovery
Clinical Development
F.C.E. ARENSIA Exploratory Medicine LLC
Brain Research New Zealand
Severance Hospital
Asan Medical Center
Chulalongkorn University
Seoul National University Hospital
Hospital for Tropical Diseases, Bangkok
Khon Kaen University
The University of Hong Kong
The University of Auckland
Discovery
Clinical Development
F.C.E. ARENSIA Exploratory Medicine LLC
Brain Research New Zealand
Other Contributor(s)
Abstract
AB-506 is a potent, pan-genotypic small molecule capsid inhibitor that inhibits hepatitis B virus (HBV) pregenomic RNA encapsidation. We assessed the safety, pharmacokinetics, and antiviral activity of AB-506 in two randomized, double-blinded Phase 1 studies in healthy subjects (HS) and subjects with chronic HBV infection (CHB). Single ascending and multiple doses of AB-506 or placebo (30–1000 mg or 400 mg daily for 10 days) were assessed in HS. AB-506 or placebo was assessed at either 160 mg or 400 mg daily for 28 days in subjects with CHB. A second follow-up study examined AB-506 or placebo at 400 mg daily for 28 days in 14 Caucasian and 14 East-Asian HS. Twenty-eight days of AB-506 at 160 mg and 400 mg produced mean HBV-DNA declines from baseline of 2.1 log10 IU/ml and 2.8 log10 IU/ml, respectively. Four subjects with CHB (all Asian) had Grade 4 alanine aminotransferase (ALT) elevations (2 at each dose) as HBV DNA was declining; three events led to treatment discontinuation. In the second follow-up study, 2 Asian HS had serious transaminitis events leading to treatment and study termination. No subjects had bilirubin elevations or signs of hepatic decompensation. Conclusion: AB-506 demonstrated mean HBV-DNA declines of >2 log10; however, transient but severe ALT flares were observed in 4 Asian subjects with CHB. In the follow-up study in HS, 2 additional Asian HS had Grade 4 flares, suggesting that AB-506 hepatotoxicity contributed to the ALT elevations. The AB-506 development program was terminated because of these findings.