AASLD5035 siRNA JNJ-73763989、衣壳组装调节剂 JNJ- 的功效和安全性

StephenW

5035
siRNA JNJ-73763989、衣壳组装调节剂 JNJ- 的功效和安全性
56136379, NUCLEOS(T)IDE ANALOG (NA) 和聚乙二醇化干扰素 ALPHA-2a (PEGIFN-
α2a) 治疗慢性乙型肝炎 (CHB)：第 24 周的阶段结果
2 企鹅研究
Edward John Gane1、Ewa Janczewska2、Tetsuo Takehara3、Wan-Long Chuang4、Cheng-Yuan Peng5、Maria
Hlebowicz6、Yasuhiro Asahina7、Ting-Tsung Chang8、Ronald Kalmeijer9、John Jezorwski9、Oliver Lenz10、Thomas N.
Kakuda9、Thierry Verbinnen10、Nonko Pehlivanov9、Zacharias Anastasiou11 和 Michael Biermer10，(1)新西兰
奥克兰大学肝移植科，(2)西里西亚医科大学健康科学学院，(3)大阪
大学医学院，（4）高雄医科大学附属医院，台湾高雄，（5）中心
中国医科大学附属医院消化内科，（6）家庭医学与传染病科，
奥尔什丁瓦尔米亚和马祖里大学，(7)东京医学牙科胃肠病学和肝病学系
大学，（8）国立成功大学医学院内科，（9）杨森研究
& Development, LLC, (10)Janssen Pharmaceutica NV, (11)Janssen-Cilag Pharmaceutical
背景：2 期、开放标签、单臂、多中心 PENGUIN 研究 (NCT04667104) 评估了疗效
JNJ-3989、JNJ-6379、NA 和 PegIFN-α2a 在病毒学抑制 (VS)、乙型肝炎 e 中治疗的安全性和安全性
抗原阳性 (HBeAg+) 或阴性 (HBeAg-) 乙型肝炎表面抗原 (HBsAg) >100 IU/mL 的 CHB 患者。
在这里，我们展示了直至治疗结束（第 24 周 [W24]）的结果。方法：NA 患者接受 JNJ-3989
和 JNJ-6379（由于协议修订，一些没有开始/停止）24 周，添加了 PegIFN-α2a
在最后 12 周的治疗期间。主要终点是 HBsAg 降低的患者比例
W24 时基线 (BL) ≥ 2 log10 IU/mL。来自 BL 的病毒标志物变化和满足的患者比例
NA 停止标准（HBsAg <10 IU/mL、HBeAg-、HBV DNA < 定量下限 [LLOQ] 和丙氨酸
还评估了 W24 的转氨酶 <3× 正常上限）。结果：共有 48 个 HBeAg+ (n=11) 和
入组 HBeAg- (n=37) VS CHB 患者。 31 名 (64.6%) 患者达到 HBsAg 的主要终点
W24 时减少≥2 log10 IU/mL，1 (2.1%) 患者实现血清清除 (HBsAg <0.05 IU/mL)。 JNJ-
3989±JNJ-6379+NA 导致平均 (SE) HBsAg 从 BL (3.27 [0.09] log10 IU/mL) 变化为 -1.43 (0.07) log10
第 12 周时的 IU/mL 和第 24 周时的 -2.18 (0.08) log10 IU/mL（图）。 44 名 (91.7%) 和 23 名 (47.9%) 患者出现 HBsAg
第 24 周时分别​​ <100 和 <10 IU/mL。对于 HBeAg+ 患者，HBeAg 的平均 (SE) 变化为 -0.68 (0.09) log10
第 12 周时 IU/mL，第 24 周时为 -0.72 (0.11) log10 IU/mL。在 11 名 HBeAg+ 患者中，4 名 (36.4%) 和 3 名 (27.3%) 达到 HBeAg
分别在第 12 周和第 24 周血清清除。在第 24 周，15 名 (31.3%) 患者符合预定义的 NA 停止标准。在所有
不符合 NA 标准的患者，76.0% 未能达到 HBsAg <10 IU/mL； HBeAg+ 患者的 HBeAg 缺失
血清清除是主要原因（72.7%）。所有治疗均安全且耐受性良好；不良事件 (AE) 和
从 W12 到 W24 的实验室异常符合 PegIFN-α2a 的已知安全性。没有
严重的 AE，只有 1 例 AE（4 级中性粒细胞减少）导致 PegIFN-α2a 停药。结论：添加 JNJ-
3989±JNJ-6379 和 PegIFN-α2a 到 NA 通常是安全的，并且在 PENGUIN 中耐受性良好，并导致了深刻的
HBsAg 降低和高比例的患者在 W24 达到 HBsAg <100 IU/mL。额外的抗病毒作用
该方案中的 PegIFN-α2a 需要进一步评估。
披露：
发布时未提供的披露信息：Tetsuo Takehara

StephenW

5035
EFFICACY AND SAFETY OF siRNA JNJ-73763989, CAPSID ASSEMBLY MODULATOR JNJ-
56136379, NUCLEOS(T)IDE ANALOG (NA), AND PEGYLATED INTERFERON ALPHA-2a (PEGIFN-
α2a) FOR TREATMENT OF CHRONIC HEPATITIS B (CHB): WEEK 24 RESULTS FROM THE PHASE
2 PENGUIN STUDY
Edward John Gane1, Ewa Janczewska2, Tetsuo Takehara3, Wan-Long Chuang4, Cheng-Yuan Peng5, Maria
Hlebowicz6, Yasuhiro Asahina7, Ting-Tsung Chang8, Ronald Kalmeijer9, John Jezorwski9, Oliver Lenz10, Thomas N.
Kakuda9, Thierry Verbinnen10, Nonko Pehlivanov9, Zacharias Anastasiou11 and Michael Biermer10, (1)New Zealand
Liver Transplant Unit, University of Auckland, (2)Faculty of Health Sciences, Medical University of Silesia, (3)Osaka
University Graduate School of Medicine, (4)Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, (5)Center for
Digestive Medicine, China Medical University Hospital, (6)Department of Family Medicine and Infectious Diseases,
University of Warmia and Mazury in Olsztyn, (7)Department of Gastroenterology and Hepatology, Tokyo Medical Dental
University, (8)Department of Internal Medicine, National Cheng Kung University Medical College, (9)Janssen Research
& Development, LLC, (10)Janssen Pharmaceutica NV, (11)Janssen-Cilag Pharmaceutical
Background: The phase 2, open-label, single-arm, multicenter PENGUIN study (NCT04667104) assessed the efficacy
and safety of treatment with JNJ-3989, JNJ-6379, NA, and PegIFN-α2a in virologically suppressed (VS), hepatitis B e
antigen positive (HBeAg+) or negative (HBeAg-) CHB patients with hepatitis B surface antigen (HBsAg) >100 IU/mL.
Here, we present the results up to end of treatment (Week 24 [W24]). Methods: Patients on NA received JNJ-3989
and JNJ-6379 (some did not start/discontinued due to protocol amendment) for 24 weeks with PegIFN-α2a added
during the final 12 weeks of treatment. The primary endpoint was the proportion of patients with HBsAg reduction from
baseline (BL) of ≥2 log10 IU/mL at W24. Changes in viral markers from BL and the proportion of patients meeting
NA stopping criteria (HBsAg <10 IU/mL, HBeAg-, HBV DNA <lower limit of quantitation [LLOQ], and alanine
transaminase <3× upper limit of normal) at W24 were also assessed. Results: A total of 48 HBeAg+ (n=11) and
HBeAg- (n=37) VS CHB patients were enrolled. Thirty-one (64.6%) patients met the primary endpoint of HBsAg
reduction ≥2 log10 IU/mL at W24, and 1 (2.1%) patient achieved seroclearance (HBsAg <0.05 IU/mL). JNJ-
3989±JNJ-6379+NA resulted in mean (SE) HBsAg changes from BL (3.27 [0.09] log10 IU/mL) of -1.43 (0.07) log10
IU/mL at W12 and -2.18 (0.08) log10 IU/mL at W24 (Figure). Forty-four (91.7%) and 23 (47.9%) patients had HBsAg
<100 and <10 IU/mL at W24, respectively. For HBeAg+ patients, mean (SE) changes in HBeAg were -0.68 (0.09) log10
IU/mL at W12 and -0.72 (0.11) log10 IU/mL at W24. Of 11 HBeAg+ patients, 4 (36.4%) and 3 (27.3%) reached HBeAg
seroclearance at W12 and W24, respectively. At W24, 15 (31.3%) patients met predefined NA stopping criteria. Of all
patients not meeting NA criteria, 76.0% failed to attain HBsAg <10 IU/mL; of HBeAg+ patients, missing HBeAg
seroclearance was the leading reason (72.7%). All treatments were safe and well tolerated; adverse events (AEs) and
laboratory abnormalities from W12 to W24 were in line with the known safety profile of PegIFN-α2a. There were no
serious AEs, and only 1 AE (grade 4 neutropenia) led to discontinuation of PegIFN-α2a. Conclusion: Addition of JNJ-
3989±JNJ-6379 and PegIFN-α2a to NA was generally safe and well tolerated in PENGUIN and resulted in profound
HBsAg reduction and a high proportion of patients achieving HBsAg <100 IU/mL at W24. The additional antiviral effect
of PegIFN-α2a in this regimen needs further evaluation.
Disclosures:
Disclosure information not available at the time of publication: Tetsuo Takehara