Arbutus宣布與AB-729一起在慢性乙型肝炎受試者中提供其他可靠

StephenW

Arbutus Announces Additional Robust HBsAg Decline Data with AB-729 in Chronic Hepatitis B Subjects
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November 16, 2020 07:00 ET | Source: Arbutus Biopharma Corporation

Data released today expands on November 15, 2020 AASLD presentation

Repeat dosing of 60 mg AB-729 every 4 weeks resulted in robust and continuous mean declines in HBsAg decline at week 20 (-1.71 log10IU/mL, N=7) and further reductions continued beyond week 20 (-1.84 log10 IU/mL, N=3)

In HBV DNA positive subjects, a single 90 mg AB-729 dose resulted in robust mean declines in HBsAg (-1.02 log10 IU/mL), HBV DNA (-1.53 log10 IU/mL), HBV RNA and HBcrAg at week 12

Results support advancement into Phase 2 combination clinical trials with AB-729 dosing as infrequently as every 8 or 12 weeks

Conference Call and Webcast Scheduled Today at 8:00 am ET

WARMINSTER, Pa., Nov. 16, 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 announced additional clinical data from an ongoing Phase 1a/1b clinical trial (AB-729-001) with AB-729, its proprietary GalNAc delivered RNAi compound.

The new data described today expands on the presentation entitled Safety and pharmacodynamics of the GalNAc-siRNA AB-729 in subjects with chronic hepatitis B infection, recorded on October 14, 2020 and presented on November 15, 2020 by Professor Man-Fung Yuen, D.Sc., M.D., Ph.D., from the University of Hong Kong at The Liver Meeting Digital ExperienceTM, The American Association for the Study of Liver Diseases (AASLD) Meeting.

The new data summarized below include HBsAg data for the complete 60 mg every 4 weeks multi-dose cohort (N=7) at week 20, and the first results for the AB-729 90 mg single-dose cohort of HBV DNA positive subjects (N=5).

William Collier, President and Chief Executive Officer of Arbutus, stated, “The positive data described today, together with the strong safety and efficacy results presented by Professor Yuen at AASLD yesterday, are encouraging and continue to support our confidence in the therapeutic value of AB-729 as we plan to move into Phase 2 clinical trials.”

Summary of new data

Repeat dosing of AB-729 60 mg every 4 weeks results in continuous declines in mean HBsAg through week 20 (Cohort E)
        Mean (SE) Week 16
N=7        Mean (SE) Week 20
N=7        Mean (SE) Week 24
N=3
Δlog10 HBsAg (IU/mL)        -1.44 (0.18)        -1.71 (0.18)        -1.84 (0.10)

Dr. Gaston Picchio, Chief Development Officer at Arbutus stated, “Further follow up of the 60 mg every 4 weeks multi-dose cohort confirmed continuous reductions in mean HBsAg at week 20 (N=7), and in a subset of subjects (N=3) beyond this time point, while being generally safe and well tolerated. Additionally, the mean HBsAg declines and slopes of declines are similar between single doses and repeat doses of AB-729 up to week 12. Importantly, this suggests that dosing AB-729 as frequently as every 4 weeks may not be necessary, and that AB-729 has the potential to be dosed every 8 weeks or even every 12 weeks. This dosing strategy is being investigated in other cohorts of the trial with results from the 60 mg every 8 week cohort expected before the end of 2020.”

AB-729 90 mg single-dose reduces HBsAg and HBV DNA in HBV DNA positive chronic Hepatitis B (CHB) subjects with mean HBsAg declines similar to those seen in HBV DNA negative subjects (Cohort D)
        Mean (SE) Week 12
N=5         
Δlog10 HBsAg (IU/mL)        -1.02 (0.13)         
Δlog10 HBV DNA (IU/mL)        -1.53 (0.24)         

Dr. Picchio added, “It is also encouraging to observe that a single 90 mg dose of AB-729 is capable of reducing HBsAg in HBV DNA positive subjects to the same extent achieved in other single-dose HBV DNA negative cohorts. Further, a single 90 mg AB-729 dose substantially reduced HBV DNA as well as HBV RNA and HBcrAg.”

AB-729 was safe and well tolerated after single and repeat doses

    No serious adverse events or discontinuations due to adverse events
    No treatment-related Grade 3 or 4 adverse events

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宣布與AB-729一起在慢性乙型肝炎受試者中提供其他可靠的HBsAg下降數據
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東部時間2020年11月16日07:00 |資料來源：楊梅生物製藥公司

今天發布的數據將於2020年11月15日AASLD演示文稿擴展

每4週重複給藥60 mg AB-729，導致第20週HBsAg下降持續且穩定的平均下降（-1.71 log10IU / mL，N = 7），並且進一步下降持續到第20週（-1.84 log10 IU / mL N = 3）

在HBV DNA陽性受試者中，在第12週，單次90 mg AB-729劑量導致HBsAg（-1.02 log10 IU / mL），HBV DNA（-1.53​​ log10 IU / mL），HBV RNA和HBcrAg均值平均下降

結果支持每隔8或12週就很少使用AB-729劑量進行2期聯合臨床試驗

美國東部時間今天上午8:00安排電話會議和網絡廣播

賓夕法尼亞州沃明斯特，2020年11月16日（全球新聞）-臨床階段生物製藥公司Arbutus Biopharma Corporation（Nasdaq：ABUS），也是一家臨床階段的生物製藥公司，主要致力於為慢性乙肝病毒（HBV）感染者開發治療方法作為治療冠狀病毒（包括COVID-19）的療法，今天宣布了正在進行的1a / 1b階段臨床試驗（AB-729-001）的其他臨床數據，其中包括其專有的GalNAc交付的RNAi化合物AB-729。

今天描述的新數據擴展了2020年10月14日記錄並於2020年11月15日發表的題為GalNAc-siRNA AB-729在患有慢性乙型肝炎感染的受試者中的安全性和藥效學的演示文稿香港大學.Sc。，MD。Ph.D.，美國肝臟疾病研究協會（AASLD）會議，The Liver Meeting Digital ExperienceTM。

以下總結的新數據包括第20週每4週完整劑量60 mg每4週（N = 7）的HBsAg數據，以及AB-729 90 mg單劑量HBV DNA陽性受試者的第一個結果（ N = 5）。

Arbutus總裁兼首席執行官William Collier表示：“今天描述的積極數據以及Yuen教授昨天在AASLD上發表的強勁安全性和有效性結果令人鼓舞，並將繼續支持我們對AB的治療價值的信心-729，因為我們計劃進入2期臨床試驗。”

新數據匯總

每4週重複服用AB-729 60 mg，導致第20週的平均HBsAg持續下降（組E）
平均（東南）第16週
N = 7平均（SE）第20週
N = 7平均（SE）第24週
N = 3
Δlog10HBsAg（IU / mL）-1.44（0.18）-1.71（0.18）-1.84（0.10）

Arbutus首席開發官Gaston Picchio博士說：“每4週多劑量隊列進一步隨訪60 mg，證實在第20週（部分= 7），平均HBsAg持續降低（N = 7）。 = 3）超出此時間點，同時通常是安全的並且具有良好的耐受性。此外，直到第12週為止，單次劑量和重複劑量的AB-729之間的平均HBsAg下降和下降斜率相似。重要的是，這表明不需要每4週一次頻繁地給藥AB-729，並且AB -729有可能每8週甚至每12週給藥一次。該劑量策略正在其他試驗組中進行研究，預期在2020年底之前每8週組60 mg的結果。”

AB-729 90 mg單劑量可降低HBV DNA陽性慢性乙型肝炎（CHB）受試者的HBsAg和HBV DNA，其平均HBsAg下降與HBV DNA陰性受試者相似（組D）
平均（SE）第12週
N = 5
Δlog10HBsAg（IU / mL）-1.02（0.13）
Δlog10HBV DNA（IU / mL）-1.53​​（0.24）

Picchio博士補充說：“觀察到90毫克的AB-729劑量能夠降低HBV DNA陽性受試者的HBsAg，達到與其他單劑量HBV DNA陰性隊列相同的程度，這也令人鼓舞。此外，單次90 mg AB-729劑量可大大降低HBV DNA以及HBV RNA和HBcrAg。”

單次和重複劑量後，AB-729安全且耐受性良好

    無嚴重不良事件或因不良事件而終止
    沒有與治療有關的3或4級不良事件

臨床試驗設計總結

AB-729-001是一項正在進行的首次人體臨床試驗，由三個部分組成：

在第1部分中，將三組健康受試者以4：2隨機分配，以接受單劑量（60 mg，180 mg或360 mg）的AB-729或安慰劑。

在第2部分中，接受低於定量限的HBV DNA核苷酸治療的非肝硬化，HBeAg陽性或陰性的慢性HBV受試者（N = 6）接受單劑量（60 mg至180 mg） AB-729。第2部分中的另一個隊列包括在HBV DNA陽性慢性HBV受試者中90 mg單劑量的AB-729。

在第3部分中，慢性HBV受試者首先接受HBV DNA陰性，然後接受HBV DNA陽性，最多可接受六個月的多劑量AB-729。

關於AB-729
AB-729是一種利用Arbutus的新型共價結合N-乙酰半乳糖胺（GalNAc）輸送技術靶向肝細胞的RNA干擾（RNAi）治療劑，可實現皮下輸送。 在臨床前模型中，AB-729抑制病毒複製並減少所有HBV抗原，包括乙肝表面抗原。 減少乙型肝炎表面抗原被認為是重新喚醒患者免疫系統以應對病毒的關鍵前提。 在一項正在進行的單劑量和多劑量1a / 1b期臨床試驗中，AB-729證實了積極的安全性和耐受性數據，並有效降低了乙型肝炎表面抗原。

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Robust HBsAg Decline