Arbutus Announces Robust HBsAg Decline Data with AB-729 Dosed at 60 mg Every 8 Weeks in Chronic Hepatitis B Subjects
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December 10, 2020 07:30 ET | Source: Arbutus Biopharma Corporation
Repeat dosing of 60 mg AB-729 every 8 weeks resulted in mean HBsAg declines of –1.37 log10 (N=6) comparable to AB-729 dosed every 4 weeks (–1.44 log10, N=7, p<0.7)
AB-729 remains generally safe and well tolerated with no SAEs or treatment discontinuations in any cohort
WARMINSTER, Pa., Dec. 10, 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.
William Collier, President and Chief Executive Officer of Arbutus, stated, “Throughout 2020, Arbutus has reported data that demonstrate the robust safety and efficacy of AB-729 in multiple patient cohorts. These data support advancing AB-729 into phase 2a clinical studies in 2021 and further support our confidence in its potential to become a cornerstone drug in future combination regimens to cure chronic hepatitis B.”
Summary of new data
Repeat dosing of AB-729 60 mg every 4 and 8 weeks results in comparable declines in mean HBsAg through week 16
Δlog10 HBsAg/(SE)
(IU/mL) Mean (SE) Week 12 Mean (SE) Week 16 Mean (SE) Week 24
Cohort E Q4W (N=7) -1.10 (0.15) -1.44 (0.18) -1.84 (0.16)
Cohort F Q8W (N=7) -1.02 (0.11) -1.37* (0.08) N/A**
*Mean determined based on N=6 since one subject has not reached week 16.
**Data not yet available since none of the subjects have reached week 24.
Dr. Gaston Picchio, Chief Development Officer of Arbutus, commented, “The mean reduction in HBsAg seen at week 16 in Cohort F suggests that AB-729 could offer patients the advantage of being dosed every 8 weeks versus every 4 weeks. Further dosing should allow us to confirm this finding.”
Dr. Picchio added, “Importantly, safety continues to be unremarkable. We have not seen any related Grade 3/4 AEs or treatment-related discontinuations in any cohorts to date. In Cohort F, two subjects had asymptomatic ALT elevations not considered AEs; one subject with Grade 1 ALT elevations prior to trial entry has had intermittent Grade 2 elevations, while another subject had a transient Grade 1 elevation which resolved with continued treatment.
Further, in Cohort E, the two subjects previously reported with Grade 2 and two subjects with Grade 1 ALT elevations have improved to Grade 1 and Grade 0, respectively, after week 24. All seven subjects in the cohort have consented to continue dosing with AB-729 for an additional 6 months.”
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: 2020-12-11 10:39
