AASLD5012 siRNA JNJ-73763989 和 CAPSID 联合治疗的疗效和安全性 HBEAG

StephenW

5012
siRNA JNJ-73763989 和 CAPSID 联合治疗的疗效和安全性
HBEAG 负极中的组装调节剂 JNJ-56136379 (BERSACAPAVIR)
病毒学抑制慢性乙型肝炎患者：随访第 48 周结束
来自 REEF-2 的研究结果
Kosh Agarwal1, Maria Buti Sr.2, Florian Van Bömmel3, Pietro Lampertico4,5, Ewa Janczewska6, Marc Bourliere7,
Thomas Vanwolleghem8,9、Oliver Lenz10、Thierry Verbinnen10、Thomas N. Kakuda11、Cristiana Mayer11、John
Jezorwski11、Daniel Muenz12、Maria Beumont10、Ronald Kalmeijer11、Michael Biermer10 和 Isabelle Lonjon-Domanec10，
(1)国王学院医院肝脏研究所，(2)瓦莱德赫布伦大学医院，(3)大学医院
莱比锡，（4）胃肠病学和肝病学部，Irccs Ca' Granda 基金会，Ospedale Maggiore Policlinico，
(5)CRC“a. M. and a. Migliavacca”肝病中心病理生理学和移植科，
米兰大学，米兰，意大利，（6）西里西亚医科大学健康科学学院，（7）HÃ ́pital Saint Joseph，
（8）安特卫普大学医院（UZA），（9）病毒性肝炎研究组，实验医学实验室和
安特卫普大学儿科，(10)Janssen Pharmaceutica NV，(11)Janssen Research & Development, LLC，
(12)伊克维亚
背景：REEF-2 (NCT04129554) 评估了 JNJ-3989、JNJ-6379 和核苷（酸）的有效性和安全性
在病毒学抑制的乙型肝炎 e 抗原阴性 (HBeAg-) 慢性乙型肝炎 (CHB) 患者中使用类似物 (NA)。
方法：在这项 2b 期、双盲、多中心、安慰剂对照研究中，HBeAg-CHB 乙型肝炎患者
表面抗原 (HBsAg) >100 IU/mL NA 治疗≥2 年被随机 (2:1) 接受附加 JNJ-
3989 + JNJ-6379（活性）或安慰剂（对照）。 48 周后停止所有治疗，包括 NA
通过 48 周的随访（FU；总研究持续时间：96 周）。在这里，我们报告研究结束（EOS；FU 第 48 周 [FU
W48]) 结果。结果：随机分配的 130 名患者（85 名活动患者，45 名对照）中，121 名（81 名活动患者，40 名对照）完成了
学习。在第 48 周（第 48 周；
治疗结束； -1.89 [0.06] 与 -0.06 [0.01] log10 IU/mL）和 FU W48（EOS；-1.46 [0.07] 和 -0.49 [0.12] log10 IU/mL）。
71.1% 和 46.9% 的患者在第 48 周和第 48 周 FU 分别达到 HBsAg <100 IU/mL，
对照组分别为 2.4% 和 15.0%。 19.7% 和 14.8% 的积极组患者达到 HBsAg
W48 和 FU W48 分别 <10 IU/mL，而对照组分别为 0% 和 7.5%。研究中没有患者达到
在 FU 第 24 周（主要终点）或 FU W48 时没有重新开始 NA 的 HBsAg 消失（<0.05 IU/mL）。那些停下来的人
NA，与对照组相比，主动组中较少的患者重新开始 NA（6/77 [7.8%] vs 12/41 [29.3%]）。未使用 NA 的患者
在 FU W48 时，与对照组相比，在 HBV DNA <2000 IU/mL 且 HBsAg <100 IU/mL (31/71 [43.7%]
与 3/28 [10.7%]) 和 HBV DNA < HBsAg <100 IU/mL (12/71 [16.9%] 和 0/28 [0%]) 的定量下限。
更频繁和更明显的非治疗 ALT 耀斑（ALT ≥ 3 × 正常上限和≥ 3 × 最低点）和
在 FU 期间，对照组与活动组中观察到病毒学复发（HBV DNA >2000 IU/mL）。频率
在 FU 期间，主动组和对照组之间的不良事件发生率相似（65.5% 对 68.3%），并且没有
死亡人数。结论：使用 JNJ-3989 + JNJ-6379 + NA 治疗 48 周通常是安全的且耐受性良好。
在第 48 周停止所有治疗（包括 NA）后，没有患者达到主要终点，但 HBsAg 水平降低
并且在 FU 48 周后观察到活动臂患者的 HBV DNA 抑制更大。
披露：
发布时未提供的披露信息：Maria Beumont

StephenW

5012
EFFICACY AND SAFETY OF COMBINATION TREATMENT WITH siRNA JNJ-73763989 AND CAPSID
ASSEMBLY MODULATOR JNJ-56136379 (BERSACAPAVIR) IN HBEAG NEGATIVE
VIROLOGICALLY SUPPRESSED CHRONIC HEPATITIS B PATIENTS: FOLLOW-UP WEEK 48 END
OF STUDY RESULTS FROM REEF-2
Kosh Agarwal1, Maria Buti Sr.2, Florian Van Bömmel3, Pietro Lampertico4,5, Ewa Janczewska6, Marc Bourliere7,
Thomas Vanwolleghem8,9, Oliver Lenz10, Thierry Verbinnen10, Thomas N. Kakuda11, Cristiana Mayer11, John
Jezorwski11, Daniel Muenz12, Maria Beumont10, Ronald Kalmeijer11, Michael Biermer10 and Isabelle Lonjon-Domanec10,
(1)Institute of Liver Studies, King's College Hospital, (2)Hospital Universitario Valle De Hebrón, (3)University Hospital
Leipzig, (4)Division of Gastroenterology and Hepatology, Foundation Irccs Ca' Granda, Ospedale Maggiore Policlinico,
(5)CRC "a. M. and a. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation,
University of Milan, Milan, Italy, (6)Faculty of Health Sciences, Medical University of Silesia, (7)HÃ ́pital Saint Joseph,
(8)Antwerp University Hospital (UZA), (9)Viral Hepatitis Research Group, Laboratory of Experimental Medicine and
Pediatrics, University of Antwerp, (10)Janssen Pharmaceutica NV, (11)Janssen Research & Development, LLC,
(12)Iqvia
Background: REEF-2 (NCT04129554) assessed the efficacy and safety of JNJ-3989, JNJ-6379, and nucleos(t)ide
analogs (NA) in virologically suppressed hepatitis B e antigen negative (HBeAg-) chronic hepatitis B (CHB) patients.
Methods: In this phase 2b, double-blind, multicenter, placebo-controlled study, HBeAg- CHB patients with hepatitis B
surface antigen (HBsAg) >100 IU/mL on NA treatment for ≥2 years were randomized (2:1) to receive add-on JNJ-
3989 + JNJ-6379 (active) or placebos (control). All treatments, including NA, were discontinued after 48 weeks followed
by 48 weeks of follow-up (FU; total study duration: 96 weeks). Here, we report end of study (EOS; FU Week 48 [FU
W48]) results. Results: Of 130 patients randomized (85 active, 45 control), 121 (81 active, 40 control) completed the
study. Mean (SE) changes in HBsAg from baseline were greater in the active versus control arm at Week 48 (W48;
end of treatment; -1.89 [0.06] vs -0.06 [0.01] log10 IU/mL) and FU W48 (EOS; -1.46 [0.07] and -0.49 [0.12] log10 IU/mL).
71.1% and 46.9% of patients in the active arm achieved HBsAg <100 IU/mL at W48 and FU W48, respectively,
compared with 2.4% and 15.0% in the control arm. 19.7% and 14.8% of patients in the active arm achieved HBsAg
<10 IU/mL at W48 and FU W48, respectively, versus 0% and 7.5% in the control arm. No patients in the study achieved
HBsAg loss (<0.05 IU/mL) without restarting NA at FU Week 24 (primary endpoint) or at FU W48. Of those who stopped
NA, fewer patients in the active versus control arm restarted NA (6/77 [7.8%] vs 12/41 [29.3%]). Of patients not on NA
at FU W48, more in the active versus control arm had HBV DNA <2000 IU/mL with HBsAg <100 IU/mL (31/71 [43.7%]
vs 3/28 [10.7%]) and HBV DNA <lower limit of quantitation with HBsAg <100 IU/mL (12/71 [16.9%] and 0/28 [0%]).
More frequent and pronounced off-treatment ALT flares (ALT ≥3× upper limit of normal and ≥3× nadir) and
virologic relapses (HBV DNA >2000 IU/mL) were observed in the control versus active arm during FU. The frequency
of adverse events was similar between the active and control arms during FU (65.5% vs 68.3%), and there were no
deaths. Conclusion: Treatment with JNJ-3989 + JNJ-6379 + NA for 48 weeks was generally safe and well tolerated.
After stopping all treatments, including NA, at W48, no patient achieved the primary endpoint, but lower HBsAg levels
and greater HBV DNA suppression were observed for patients in the active arm after 48 weeks of FU.
Disclosures:
Disclosure information not available at the time of publication: Maria Beumont