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    Home > Active Ingredient News > Infection > AAC: Hepatitis B in the study of the new drug ABI-H0731 can inhibit the formation of cccDNA, is expected to completely cure hepatitis B.

    AAC: Hepatitis B in the study of the new drug ABI-H0731 can inhibit the formation of cccDNA, is expected to completely cure hepatitis B.

    • Last Update: 2020-10-10
    • Source: Internet
    • Author: User
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    Nucleoside (acid) reverse transcriptase inhibitors (NrtI) are currently standard drugs for the treatment of chronic HBV (CHB) infections, and these drugs are resistant to the virus in most patients, but rarely receive a sustained response after discontinuation of treatment.
    ABI-H0731 (731) is the first generation of HBV core inhibitors developed by Assembly Biosciences to treat chronic hepatitis B (CHB) and is currently undergoing a joint drug evaluation with NrtI in Phase 2 clinical studies.
    ABI-H0731, a new drug, has been in the process of a number of Phase II clinical studies, ABI-H0731 has seven phase II clinical trials.
    phase II study is mainly based on the use of ABI-H0731 to strengthen the treatment of chronic hepatitis B.
    , the results of the new drug ABI-H0731 Ib were published in the top infectious disease journal Animicrobial Agents and Processy.
    phase IB trial, ABI-H0731 has been shown to have effective antiviral activity in patients with chronic hepatitis B (CHB) and is currently under further evaluation in Phase 2 clinical trials.
    In its clinical pre-insotroviral cell culture system, including HepG2 derived cell line: HepG2 derived cell line: HepAD38 and HepG2 NTCP and primary liver cells (PHH), ABI-H0731 exhibited selective inhibition of hepatitis B virus replication (EC50 from 173 nM to 307 nM).
    most importantly, ABI-H0731 is able to inhibit the formation of cccDNA (the template for hepatitis B virus replication) in two EC50S from 1.84 to 7.3 m of head-on infection models.
    in the mechanism of action (MOA), the results show that ABI-H0731 is a direct-acting antiviral drug that targets the core protein of HBV and prevents pre-genome RNA (pgRNA) enshrined and subsequent DNA replication of HBV.
    when used in a separate nucleotide analogue (NrtI), ABI-H0731, in association with Entekave (ETV), appears to be able to reduce HBV DNA more quickly and deeply (above, the research and development pipeline: ABI-H0731 is in Phase II).
    ABI-H0731 and has been granted fast-track status by the FDA since late July 2018.
    its drug mechanism is to interfere with the entry of the nuclear casing, causing rcDNA to be released prematurely before it is passed to the nucleation of the cell, effectively preventing the formation of new cccDNA.
    ABI-H0731 exhibits generic genotype activity and is a suitable synergistic additive when combined with nucleotide analogants (NrtI).
    addition to the new mechanism of effect of the drug-effect nuclear, ABI-H0731 also has drug-like properties, as well as preclinical pharmacological characteristics.
    researchers believe that hepatitis B in the study of the new drug ABI-H0731 (entering Phase II) can support chronic hepatitis B patients once a day.
    overall, these data support ABI-H0731 as a clinical advance in the treatment of patients with chronic hepatitis B.
    follows the recent unveiling of preliminary Phase 2 findings at the EASL 2020 meeting.
    ABI-H0731-201 is a double-blind, placebo (Pbo) controlled study in patients with slow hepatitis B who use nucleoside (acid) reverse transcriptase inhibitors (NrtI) to inhibit viral replication.
    patients were randomly divided into ABI-H0731 (300mg QD) plus NrtI or placebo plus NrtI for 24 weeks at a 3:2 scale.
    the criteria for eligible patients are HBV DNA≤ minimum detection threshold (LLOQ) of more than 6 months and more, HBsAg> 1000 IU / mL, ALT≤5x ULN and Metavir F0-F2.
    HBV DNA is measured by COBAS TaqMan 2.0 (LLOQ s 20 IU / mL) and indoor (ASMB) semi-quantitative PCR assays (LLOQ s 5 IU / mL).
    HBV pgRNA is measured by ASMB RT-qPCR assay (LLOQ s 35 IU / mL).
    to evaluate security by reporting adverse events (AEs) and lab exceptions.
    47 e-antigen-positive (Big Sanyang) and 26 e-antigen-negative (Small Sanyang) (those using ETV to suppress the virus) included in the 201 study observed that ABI-H was completed after 24 weeks of drug use The percentages of 0731 that cause HBV-DNA to be detected are ABI-H0731 plus ETV (69%), and single-drug ETV (0%).
    16 of the 26 HBeAg-negative patients included in the study received ABI-H0731 plus nucleoside (acid) reverse transcriptase inhibitors (NrtI) and 10 received Pbo plus NrtI.
    , the average age range was 48 (34-64) years, 16 (62%) for men and 21 (81%) in Asia.
    results are shown.
    ASMB HBV DNA test showed that patients treated with ABI-H0731 plus nucleoside (acid) reverse transcriptase inhibitors (NrtI) to achieve TND were higher than the Pbo-NrtI treatment group.
    pgRNA and HBcrAg levels were lower at baseline and throughout the study, but HBsAg levels were unchanged.
    in the 202 study, among 25 patients with chronic hepatitis B who had been treated, the average HBV-DNA and RNAlog10 decreased even more when comparing single-drug ETV with ABI-H0731 and ETV.
    , the safety and tolerance of ABI-H0731 are relatively good.
    , the drug inhibited the formation of the hepatitis B virus replication template cccDNA, and has been shown in a joint ETV program to promote HBV-DNA vulsion ratio to 69% of all subjects.
    the security of the ABI-H0731 and NrtI is similar to that of Pbo and NrtI.
    both treatments are well-umed, with no serious adverse events or interruptions due to adverse events.
    all adverse events and laboratory anomalies are mild or moderate in severity.
    only one patient who received ABI-H0731 plus NrtI reported a stage 1 rash, which was resolved in the study without interruption of treatment.
    did not observe an increase in level 3 ALT.
    the data, the study concluded that HBeAg negative patients who received ABI-H0731 and NrtI had a higher proportion of HBV DNA TND during the 24-week treatment than Pbo and NrtI.
    ABI-H0731 has good security and tolerance.
    these data show that ABI-H0731 contributes to traditional treatment standards in achieving deeper viral suppression and supports the continued use of ABI-H0731-NrtI in the open-label Phase 2 study ABI-H0731-211.
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