Arbutus宣布在慢性乙型肝炎患者中显示AB-729 90毫克单剂量第12

StephenW

Arbutus Announces AB-729 90 mg Single-Dose Week 12 Data in Chronic Hepatitis B Subjects Demonstrating Significant and Continuous Reductions in HBsAg
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September 15, 2020 07:30 ET | Source: Arbutus Biopharma Corporation

Mean HBsAg reduction of 1.23 log10 IU/mL at week 12 with a favorable safety and tolerability profile

WARMINSTER, Pa., Sept. 15, 2020 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company primarily focused on developing a cure for people with chronic hepatitis B virus (HBV) infection as well as therapies to treat coronaviruses (including COVID-19), today reports continued positive data from an ongoing Phase 1a/1b clinical trial (AB-729-001) with AB-729, its proprietary GalNAc delivered RNAi compound. These new data demonstrate that in chronic HBV subjects, a single subcutaneous injection of 90 mg of AB-729 resulted in a mean HBsAg reduction of 1.23 log10 IU/mL at week 12.

William Collier, President and Chief Executive Officer of Arbutus, stated, “The 90 mg single-dose 12-week data coupled with our previously disclosed 60 mg single-dose 12-week data mean that we now have two doses which have demonstrated meaningful reductions in HBsAg with a favorable safety and tolerability profile. We are currently dosing chronic HBV subjects in four multi-dose cohorts using both the 60 mg (every 4- and 8-weeks) and 90 mg (every 8- and 12-weeks) doses to determine the optimal dosing regimen for AB-729. We believe AB-729 will potentially offer people with chronic HBV a well-tolerated low dose treatment with a minimum of injections.”

Arbutus expects to present initial results from its ongoing Phase 1a/1b clinical trial for the 60 mg multi-dose cohorts, the 90 mg single-dose cohort in HBV DNA positive subjects, as well as longer-term follow up of the 60 and 90 mg single-dose cohorts, at an upcoming scientific meeting later this year. In addition to the ongoing 60 mg multi-dose cohorts with subjects dosed at 4- and 8-weeks, the Company has also initiated 90 mg multi-dose cohorts with subjects dosed at 8- and 12-week intervals.

Mean HBsAg changes from baseline:
60 mg Single-Dose Cohort (B) (N=6)    90 mg Single-Dose Cohort (C) (N=6)
Week 12 (day 84) mean log10 IU/mL
(Standard Error of the Mean)    -0.99 (0.24)    -1.23 (0.18)

Dr. Gaston Picchio, Chief Development Officer of Arbutus, stated, “The mean HBsAg decline seen in the 90 mg single-dose cohort is consistent with that seen in prior single-dose cohorts. Importantly, the data demonstrate consistent efficacy and a favorable safety profile at this intermediate dose. These findings support the continued evaluation of the 90 mg dose in the multi-dose portion of our ongoing clinical trial.”

Summary of clinical trial design

AB-729-001 is an ongoing first-in-human clinical trial consisting of three parts:
In Part 1, three cohorts of healthy subjects were randomized 4:2 to receive single-doses (60 mg, 180 mg or 360 mg) of AB-729 or placebo.

In Part 2, non-cirrhotic, HBeAg positive or negative, chronic HBV subjects (N=6) on a background of nucleos(t)ide therapy with HBV DNA below the limit of quantitation received single-doses (60 mg to 180 mg) of AB-729. An additional cohort in Part 2 included 90 mg single-dose of AB-729 in HBV DNA positive chronic HBV subjects.

In Part 3, chronic HBV subjects, HBV DNA negative first and HBV DNA positive later, are receiving multi-doses of AB-729 for up to six months.

About AB-729

AB-729 is an RNA interference (RNAi) therapeutic targeted to hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. AB-729 inhibits viral replication and reduces all HBV antigens, including hepatitis B surface antigen in preclinical models. Reducing hepatitis B surface antigen is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. In an ongoing single- and multi-dose Phase 1a/1b clinical trial, AB-729 demonstrated positive safety and tolerability data and meaningful reductions in hepatitis B surface antigen.

StephenW

Arbutus宣布在慢性乙型肝炎患者中显示AB-729 90毫克单剂量第12周数据，证明其HBsAg显着且持续降低
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东部时间2020年9月15日07:30 |资料来源：杨梅生物制药公司

第12周的HBsAg平均减少量为1.23 log10 IU / mL，具有良好的安全性和耐受性

宾夕法尼亚州沃明斯特，2020年9月15日（全球新闻）-临床阶段生物制药公司Arbutus Biopharma Corporation（纳斯达克股票代码：ABUS），主要致力于为慢性乙型肝炎病毒（HBV）感染者以及其他人开发治疗方法治疗冠状病毒（包括COVID-19）的疗法，今天报道了一项正在进行的1a / 1b阶段临床试验（AB-729-001）的积极数据，该试验使用其专有的GalNAc传递的RNAi化合物AB-729。这些新数据表明，在慢性HBV受试者中，单次皮下注射90 mg AB-729导致第12周的HBsAg平均降低1.23 log10 IU / mL。

Arbutus总裁兼首席执行官William Collier表示：“ 90毫克单剂量12周数据加上我们之前披露的60毫克单剂量12周数据意味着我们现在有两剂已证明可有效减少剂量在HBsAg中具有良好的安全性和耐受性。我们目前正在以60毫克（每4周和8周）和90毫克（每8周和12周）的剂量分四个多剂量组对慢性HBV受试者进行给药，以确定AB-729的最佳给药方案。我们相信AB-729将有可能以最少的注射量为慢性HBV患者提供耐受性良好的低剂量治疗。”

Arbutus希望从正在进行的1a / 1b阶段临床试验中获得初步结果，该试验针对60毫克多剂量队列，HBV DNA阳性受试者的90毫克单剂量队列以及60和90的长期随访mg单剂量研究组，在今年晚些时候即将举行的科学会议上。除了正在进行的60 mg多剂量研究组（在4周和8周时给予受试者）之外，公司还发起了90 mg多剂量研究组，其受试者在8周和12周时给予给药。

HBsAg从基线的平均变化：
60 mg单剂量组（B）（N = 6）90 mg单剂量组（C）（N = 6）
第12周（第84天）平均log10 IU / mL
（平均值的标准误）-0.99（0.24）-1.23（0.18）

Arbutus首席开发官Gaston Picchio博士说：“在90 mg单剂量组中发现的HBsAg平均下降与以前的单剂量组中发现的一致。重要的是，数据证明在该中间剂量下具有一致的疗效和良好的安全性。这些发现支持在我们正在进行的临床试验的多剂量部分中继续评估90 mg剂量。”

临床试验设计总结

AB-729-001是一项正在进行的首次在人体中进行的临床试验，包括三个部分：
在第1部分中，将三组健康受试者以4：2随机分配，以接受单剂量（60 mg，180 mg或360 mg）的AB-729或安慰剂。

在第2部分中，接受低于定量限的HBV DNA核苷酸治疗的非肝硬化，HBeAg阳性或阴性，慢性HBV受试者（N = 6）接受单剂量（60 mg至180 mg） AB-729。第2部分中的另一个队列包括在HBV DNA阳性的慢性HBV受试者中90 mg单剂量的AB-729。

在第3部分中，慢性HBV受试者首先接受HBV DNA阴性，然后接受HBV DNA阳性，最多可接受六个月的多剂量AB-729。

关于AB-729

AB-729是使用Arbutus的新型共价结合N-乙酰半乳糖胺（GalNAc）递送技术靶向肝细胞的RNA干扰（RNAi）治疗剂，可实现皮下递送。在临床前模型中，AB-729抑制病毒复制并减少所有HBV抗原，包括乙肝表面抗原。减少乙型肝炎表面抗原被认为是重新唤醒患者免疫系统以应对病毒的关键前提。在一项正在进行的单剂量和多剂量1a / 1b期临床试验中，AB-729表现出积极的安全性和耐受性数据，并有效减少了乙型肝炎表面抗原。

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