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.作者: StephenW 时间: 2020-11-18 19:42