JNJ-3989三联用药48周结果在AASLD发布

sir

Background: JNJ-3989 is an siRNA designed to target all hepatitis B virus (HBV) RNAs, thereby reducing all viral
proteins. JNJ-6379 is a CAM that inhibits viral replication by inducing the formation of viral capsids devoid of
genomic material. The REEF-1 study assessed the efficacy and safety of monthly (Q4W) s.c. injections of JNJ-
3989 (3 dose levels of 40, 100, and 200mg) and/or 250mg QD oral JNJ-6379 in combination with QD oral NA in
currently not treated (CNT) or virally suppressed (VS) patients with HBeAg positive or negative CHB.
Methods: In this Phase 2b, multicenter, active-controlled study, CHB patients (N=470) were randomized (2:2:2:2:1:1)
to 6 arms (see Figure) and dosed for a 48-week double-blind PBO-controlled treatment period and 48 weeks of
follow up (FU). The primary endpoint was the proportion of patients meeting NA stopping criteria (ALT <3x ULN, HBV
DNA <LLOQ, HBeAg-negative [<LLOQ], and HBsAg <10 IU/mL) at Week 48. Week 48 data are shown here; Week
72 data (FU Week 24) will be presented.
Results: Patients in REEF-1 were 66% male, 52% White, 41% Asian, 70% HBeAg negative, and 63% VS at
baseline (BL). The proportions of patients achieving primary endpoint are depicted in the Figure, with the highest
proportion (19.1%) in the JNJ-3989 200mg + NA arm. The JNJ-3989 200mg + NA arm had the highest proportion patients (33%) achieving HBsAg levels <10 IU/mL by Week 44, and 72% reached <100 IU/mL. Significant mean
log10 reductions from baseline to end of treatment in HBsAg were observed with JNJ-3989 200, 100, and 40mg +
NA (with dose-response pattern), and JNJ-3989 + JNJ-6379 + NA (–2.58, –2.09, – 1.50, and –1.76 log10 IU/mL),
but not with PBO or JNJ-6379 + NA (–0.22 and –0.07 log10IU/mL); <3% of patients achieved HBsAg loss. Levels
of hepatitis B core-related antigen (HBcrAg), HBV RNA, and HBV DNA (in patients not currently treated at BL), and
HBeAg (in HBeAg-positive patients) were reduced on treatment; <1% of patients achieved HBeAg loss. All
regimens within this long-term, triple therapy study were generally well tolerated and safe; 2 of 10 reported SAEs
(ALT flare and rhabdomyolysis) were considered related to study drug. Treatment discontinuation rates were low
(≤6.3% in all arms).
Conclusion: JNJ-3989 showed a dose dependent response with up to 19.1% meeting the primary endpoint.JNJ-3989 showed a dose dependent response with up to 19.1% meeting the primary endpoint at
Week 48 compared to 0% in the JNJ-6379 + NA and 2.2% in the PBO + NA arm. Reduction of HBsAg levels was
greatest with JNJ-3989 200mg.


结果:jnj3989+jnj6379+NA三联用药48周降低1.7log,不及jnj3989+NA降低2.6log,33%的人群hbsag低于10，但离转阴还差的远，没有干扰素的方案是没戏了，目前强生后面进行的几个临床实验都是包含干扰素的联合用药方案，vir2218联合干扰素24周降低3log,RNAi没有干扰素是不行了，单独用药会出现平台期，延长时间降低2.5log算是极限了，明年看gsk836的结果，应该会好很多

齐欢畅

光jiang病毒效果不好，因为免疫系统已经放弃抵抗了，所以没有再发起斗争的勇气。需要干扰素唤醒免疫系统

newchinabok

齐欢畅 发表于 2021-11-7 17:41
光jiang病毒效果不好，因为免疫系统已经放弃抵抗了，所以没有再发起斗争的勇气。需要干扰素唤醒免疫系统 ...

正解，北京佑安医院陈新月教授最看重的是用干挠素，肝功能发生不正常，这是良好的免疫系统激活表现

齐欢畅

newchinabok 发表于 2021-11-7 19:35
正解，北京佑安医院陈新月教授最看重的是用干挠素，肝功能发生不正常，这是良好的免疫系统激活表现 ...

古巴新药，就有这么一个过程，我觉得有戏。