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LBP30
Antiviral activity and safety of the hepatitis B core inhibitor ABIH0731
administered with a nucleos(t)ide reverse transcriptase
inhibitor in patients with HBeAg-positive chronic hepatitis B
infection in a long-term extension study
Man-Fung Yuen1, Kosh Agarwal2, Xiaoli Ma3, Tuan Nguyen4,
Eugene R. Schiff5, Hie-Won Hann6, Douglas Dieterich7,
Ronald Nahass8, James Park9, Sing Chan10, Steven-Huy Han11,
Edward Gane12, Michael Bennett13, Katia Alves14, Hany Zayed14,
Qi Huang14, Richard Colonno14, Steven Knox14, Luisa Stamm14,
Maurizio Bonacini15, Ira Jacobson9, Walid Ayoub16, Frank Weilert17,
Natarajan Ravendhran18, Alnoor Ramji19, Paul Kwo20,
Magdy Elkhashab21, Tarek Hassanein22, Ho Bae23, Jacob Lalezari15,
Scott Fung24, Mark Sulkowski25. 1The University of Hong Kong,
Department of Medicine, Hong Kong, China; 2Institute of Liver Studies,
King’s College Hospital, London, United Kingdom; 3Office of Xiaoli Ma,
Philadelphia, United States; 4T Nguyen Research and Education, Inc., San
Diego, United States; 5Schiff Center for Liver Diseases, University of
Miami School of Medicine, Miami, United States; 6Thomas Jefferson
University Hospital, Philadelphia, United States; 7Icahn School of
Medicine, Mount Sinai Hospital, Department of Medicine, Division of
Liver Diseases, New York, United States; 8Infectious Disease Care,
Hillsborough, United States; 9New York University Langone Medical
Center, New York, United States; 10Sing Chan MD, New York, United
States; 11Pfleger Liver Institute, University of California, Los Angeles,
United States; 12Auckland Clinical Studies Ltd, Auckland, New Zealand;
13Medical Associates Research Group, San Diego, United States;
14Assembly Biosciences Inc., South San Francisco, United States; 15Quest
Clinical Research, San Francisco, United States; 16Cedars-Sinai Medical
Center, Los Angeles, United States; 17Waikato Hospital, Hamilton, NewZealand; 18Digestive Disease Associates, Catonsville, United States;
19Providence Health Care Research Institute, Vancouver, Canada;
20Stanford University Medical Center, Stanford, United States; 21Toronto
Liver Centre, Toronto, Canada; 22Southern California Research Center,
Coronado, United States; 23Asian Pacific Liver Center, Los Angeles, United
States; 24University of Toronto, Toronto, Canada; 25Johns Hopkins
University School of Medicine, Baltimore, United States
Email: [email protected].
Background and aims: ABI-H0731 (731) is a first-generation HBV
core inhibitor in development for the treatment of chronic hepatitis B
infection (CHB). In the Phase 2a studies 202 and 201, treatment naïve
(TN) and virally suppressed (VS) HBeAg-positive patients (pts) with
CHB were randomized 1:1 to 731 or placebo (Pbo) with NrtI in a
blinded manner for 24 weeks. The combination of 731+NrtI was well
tolerated and demonstrated faster and greater reductions in HBV DNA
and pgRNA than NrtI alone. Following study completion, eligible pts
entering an open-label extension study 211 received 731+NrtI for up
to an additional 76 weeks. Here we report the updated data from
study 211 through the current last reported observation.
Method: For TN pts, HBV DNA was measured by COBAS TaqMan 2.0
(LLOQ = 20 IU/mL) and pgRNA by an in-house quantitative PCR assay
(LLOQ = 135 U/mL). For VS pts, HBV DNA was measured by an inhouse
semi-quantitative PCR assay (LLOD = 5 IU/mL) and pgRNA by
an in-house semi-quantitative RT-PCR assay (LLOD = 5 IU/mL). For all
pts, quantitative HBeAg and HBsAg were measured by Abbott
Architect (LLOQ = 0.11 IU/mL and 0.05 IU/mL, respectively) and
HBcrAg by Lumipulse G (LLOD = 1 kU/mL). Safety was assessed by
adverse events (AEs) and laboratory parameters.
Results: Of the 23 TN pts from study 202, median (range) treatment
duration 57 (36–83) weeks, 21 pts have DNA declines to <100 IU/mL
and 6 pts have pgRNA declines to <500 U/mL. Declines of ≥1 log or at
<LLOQ in HBeAg, HBcrAg and HBsAg have been observed in 6, 8 and 3
pts, respectively. Of the 43 VS pts from study 201, median (range)
treatment duration 58 (30–81) weeks, 34 and 21 pts have now
achieved DNA and pgRNA <5 IU/mL, respectively. In addition, 29 pts
have HBeAg <5 IU/mL, 27 pts have HBcrAg <500 kU/mL and 4 pts have
HBsAg <1000 IU/mL. During the first 24weeks of study 211, AEs were
reported by 47% (31/66) pts, most of which were Grade 1 or 2. There
were no SAEs or AEs leading to study drug discontinuation. The only
AE reported by >5% was upper respiratory tract infection (4 pts, 6%).
Most laboratory abnormalities were Grade 1 or 2. Transient or
intermittent Grade 3 elevations in ALT were observed in 2 pts (3%),
both of whom continue on study drug.
Conclusion: Results from the ongoing Phase 2a extension study
demonstrate continued declines in HBV DNA, pgRNA and viral
antigens in pts treated with 731+NrtI. 731 continues to exhibit a
favorable safety and tolerability profile in pts treated for over 1 year.
The data support the continued development of 731. |
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