AASLD5047 在 HBEAG 的延长随访期间维持乙型肝炎病毒控制- 停止

StephenW

5047
在 HBEAG 的延长随访期间维持乙型肝炎病毒控制-
停止使用 NUCLEOS(T)IDE 类似物的慢性乙型肝炎 (CHB) 受试者
(NA) 完成 AB-729 治疗后和 HBEAG+ 受试者的治疗
NA 疗法
Man-Fung Yuen1, Jacinta A. Holmes2, Simone I. Strasser3, Apinya Leerapun4, Wattana Sukeepaisarnjaroen5, Pisit
Tangkijvanich6、Varun Sharma7、Elina Medvedeva7、Emily P Thi8、Gaston R. Picchio7、Timothy Eley7 和 Karen Sims7，
(1)香港大学医学系，(2)墨尔本圣文森特医院消化内科，
澳大利亚，(3)A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney NSW, Australia,
(4)清迈大学，泰国清迈，(5)泰国孔敬大学斯利那加林医院，(6)中心
卓越的肝炎和肝癌，朱拉隆功大学医学院，曼谷，泰国，(7)临床
Development, Arbutus Biopharma, Warminster, PA USA, (8)Research/Discovery, Arbutus Biopharma, Warminster, PA
美国
背景：AB-729 是一种结合 GalNAc 的单触发 siRNA 治疗剂，靶向所有 HBV RNA 转录物，
导致病毒复制和所有病毒抗原的抑制。 AB-729目前处于2期临床开发中
与其他药物联合治疗慢性乙型肝炎。研究 AB-729-001 评估了 AB-729 的不同方案
48 周 (W) 与正在进行的 NA 治疗相结合。在这里，我们报告来自所有受试者的早期随访 (FU) 数据
专用 HBeAg+ Cohort K（均已完成 AB-729 治疗期），以及 9
来自其他研究队列的受试者，他们选择在最后一剂 AB-729 后至少 6 个月停止 NA 治疗
可选的 NA 中止 (d/c) 期的一部分。方法：队列 K 是一个专门的 HBeAg+ 队列 (N=7)
AB-729 90mg 每 8W 为 48W。由于药物供应，7 名受试者中有 2 名接受了计划的 6 剂 AB-729 中的 5 剂，并且
现在所有科目都在FU期。 AB-729-001 研究中接受 AB-729 治疗 48W 的所有受试者均接受评估
在最后一剂 AB-729 后至少 24W 有资格获得 NA d/c。 NA d/c 标准包括 ALT <2×ULN、HBeAg-、
连续 2 次就诊时检测不到 HBV DNA，且 HBsAg <100 IU/mL。安全性和病毒学评估（包括
在 Cohort K 给药和治疗后，每 4W 评估一次 HBV DNA、HBsAg、HBV RNA、HBcrAg、HBeAg）
FU，并且在 NA d/c 之后每 2-4W。结果：在队列 K 中，HBsAg 相对于基线的平均 (SE) log10 变化为 -2.51
第 48 周为 (0.57) IU/mL，第 12 周为 -2.26 (0.68) IU/mL（每个 N=5），其中 2 名受试者达到 HBsAg 水平
第 44 周和第 12 周的 FU 低于定量限 (BLQ)（治疗前 HBsAg 水平分别为 600.1 IU/mL 和 545.2
IU/mL）。迄今为止，没有 Cohort K 受试者符合 NA d/c 标准。来自队列 E、F、G 和 I 的九个科目
选择停止 NA；这些受试者的基线特征以前已经报道过。迄今为止，所有 9 个科目
已完成 16W 至 40W 的 FU 关闭所有 HBV 治疗。关键的 HBV DNA 和 HBsAg 值显示在
桌子。当 HBV DNA 达到 4670 时，一名受试者在 NA d/c FU W20 访问后根据研究者的请求重新开始 NA
国际单位/毫升；受试者无症状，ALT保持正常。没有受试者符合协议定义的 NA 重启
标准。在最后一个可用时间点，所有 HBV DNA 水平均 <1000 IU/mL，HBsAg 水平仍远低于上市前
所有科目的学习水平。结论：AB-729 治疗导致 HBeAg+ 受试者的 HBsAg 显着下降，
2 名受试者达到 HBsAg BLQ。 HBeAg- HBsAg <100 的受试者在 NA+AB-729 治疗后的 NA d/c
IU/mL 耐受性良好，可在所有治疗后 40 周内持续保持低 HBV DNA 和 HBsAg 水平，
通过免疫控制提示新的病毒设定点

StephenW

5047
HEPATITIS B VIRAL CONTROL MAINTAINED DURING EXTENDED FOLLOW UP OF HBEAG-
CHRONIC HEPATITIS B (CHB) SUBJECTS WHO DISCONTINUED NUCLEOS(T)IDE ANALOGUE
(NA) THERAPY AFTER COMPLETION OF AB-729 TREATMENT, AND IN HBEAG+ SUBJECTS STILL
ON NA THERAPY
Man-Fung Yuen1, Jacinta A. Holmes2, Simone I. Strasser3, Apinya Leerapun4, Wattana Sukeepaisarnjaroen5, Pisit
Tangkijvanich6, Varun Sharma7, Elina Medvedeva7, Emily P Thi8, Gaston R. Picchio7, Timothy Eley7 and Karen Sims7,
(1)Department of Medicine, The University of Hong Kong, (2)Gastroenterology, St. Vincent's Hospital, Melbourne,
Australia, (3)A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney NSW, Australia,
(4)Chiang Mai University, Chiang Mai, Thailand, (5)Srinagarind Hospital, Khon Kaen University, Thailand, (6)Center of
Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, (7)Clinical
Development, Arbutus Biopharma, Warminster, PA USA, (8)Research/Discovery, Arbutus Biopharma, Warminster, PA
USA
Background: AB-729 is a GalNAc-conjugated single trigger siRNA therapeutic that targets all HBV RNA transcripts,
resulting in suppression of viral replication and all viral antigens. AB-729 is currently in Phase 2 clinical development in
combination with other agents for the treatment of CHB. Study AB-729-001 assessed different regimens of AB-729 for
48 weeks (W) in combination with ongoing NA therapy. Here we report early follow-up (FU) data for all subjects from
the dedicated HBeAg+ Cohort K (all have completed the AB-729 treatment period), and extended FU data for the 9
subjects from other study Cohorts who elected to stop NA therapy at least 6 months after their last dose of AB-729 as
part of an optional NA discontinuation (d/c) period. Methods: Cohort K is a dedicated HBeAg+ cohort (N=7) dosed with
AB-729 90mg every 8W for 48W. Two of 7 subjects received 5 of the planned 6 AB-729 doses due to drug supply, and
all subjects are now in the FU period. All subjects in the AB-729-001 study who received AB-729 for 48W are assessed
for eligibility for NA d/c at least 24W after their last dose of AB-729. NA d/c criteria include ALT <2×ULN, HBeAg-,
HBV DNA undetectable, and HBsAg <100 IU/mL on 2 consecutive visits. Safety and virologic assessments (including
HBV DNA, HBsAg, HBV RNA, HBcrAg, HBeAg) are assessed every 4W during Cohort K dosing and post-treatment
FU, and every 2-4W after NA d/c. Results: In Cohort K, the mean (SE) log10 change from baseline in HBsAg was -2.51
(0.57) IU/mL at W48 and -2.26 (0.68) IU/mL at FU W12 (N=5 each), with 2 of these subjects achieving HBsAg levels
below the limit of quantitation (BLQ) at W44 and at FU W12 (pre-treatment HBsAg levels were 600.1 IU/mL and 545.2
IU/mL, respectively). No Cohort K subjects have met NA d/c criteria to date. Nine subjects from Cohorts E, F, G, and I
elected to stop NAs; baseline characteristics of these subjects have been reported previously. To date, all 9 subjects
have completed between 16W and 40W of FU off all HBV therapy. Key HBV DNA and HBsAg values are shown in the
Table. One subject restarted NA per Investigator request after the NA d/c FU W20 visit when HBV DNA reached 4670
IU/mL; the subject was asymptomatic and ALT remained normal. No subjects have met the protocol-defined NA restart
criteria. At the last available timepoint, all HBV DNA levels are <1000 IU/mL and HBsAg levels remain well below pre-
study levels for all subjects. Conclusion: AB-729 treatment leads to marked HBsAg declines in HBeAg+ subjects, with
2 subjects achieving HBsAg BLQ. NA d/c after NA+AB-729 treatment in HBeAg- subjects who achieve HBsAg <100
IU/mL is well-tolerated and results in sustained low HBV DNA and HBsAg levels up to 40 weeks off all therapy,
suggestive of new viral set points via immune control

newchinabok

目前新药数据都大白于天下了，就看联合，治愈一部分人，这个十年可能就这样了