WARMINSTER, Pa., March 26, 2020 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS), a Hepatitis B Virus (HBV) therapeutic solutions company, today announced positive preliminary results from a Phase 1a/1b clinical trial (AB-729-001) in healthy subjects and two cohorts of chronic hepatitis B subjects on nucleos(t)ide antiviral therapy, all of whom received a single subcutaneous injection of AB-729. AB-729-001 is an ongoing Phase 1a/1b clinical trial designed to determine the most effective dose and dosing interval for use in future Phase 2 combination clinical trials.
William Collier, President and Chief Executive Officer of Arbutus, stated, “These encouraging preliminary results demonstrate that AB-729 is a potent RNAi agent capable of reducing HBsAg plasma levels and support its further development as a treatment for people living with chronic hepatitis B. Our plan is to move forward into the multiple dose portion of the clinical trial with the 60 mg dose and, in parallel, to explore additional single dose cohorts beginning with the 90 mg dose. We intend to initiate these cohorts as soon as possible; however, at this point, it is not possible to predict if the COVID-19 pandemic will negatively impact our plans and timelines. Provided we can execute our clinical trials as planned, we continue to expect these data sets in the second half of the year.”
Mean HBsAg changes from baseline:
60 mg Cohort (N=6) 180 mg Cohort (N=4)
Day 29 mean log10 IU/mL (SE) -0.24# (0.13) -0.81* (0.38)
Week 12 mean log10 IU/mL (SE) NA -0.98 (0.22)
#In the 60 mg cohort, the maximum Day 29 decline was -0.62 log10.
*In the 180 mg cohort, excluding one subject with a HBsAg decline of -1.94 log10, the mean (SE) reduction for the remaining 3 subjects was -0.44 log10 (0.07) at Day 29 and -0.77 log10 (0.06) at Week 12.
Dr. Gaston Picchio, Chief Development Officer of Arbutus, stated, “AB-729 dosed at either 60 mg or 180 mg in chronic hepatitis B subjects was generally safe and well tolerated and resulted in meaningful reductions in HBsAg levels. Additionally, after a single 180 mg dose, HBsAg levels continued to decline well beyond Week 12, suggesting that AB-729 has the potential to be dosed less frequently than every four weeks.”
Dr. Picchio added, “The subject receiving the 180 mg dose who experienced the highest HBsAg decline also experienced a Grade 3 ALT/AST flare. While the flare may have been related to an acute gastroenteritis and self-medication, we believe evaluating at least one additional single dose cohort starting at 90 mg is appropriate and should allow us to determine if a mid-dose would provide the greatest benefit in terms of safety, efficacy and dosing interval.”
Preliminary safety summary in healthy subjects
In the 60 mg, 180 mg and 360 mg cohorts, no serious adverse events (SAEs) were observed; most adverse events (AEs) were mild (13/15) and considered unrelated (12/15) to AB-729.
Two subjects in the 360 mg cohort had asymptomatic, reversible Grade 3 ALT elevations assessed as related to AB-729. Neither subject had meaningful changes in any other laboratory parameter excepting Grade 1 or 2 AST elevation.
There were no other clinically relevant abnormalities in laboratory tests, ECGs, or vital signs.
Preliminary safety and efficacy summary in chronic HBV subjects
HBsAg declines were observed in all 4 subjects (3 HBeAg negative, 1 HBeAg positive) in the 180 mg cohort, with a mean HBsAg (SE) log10 reduction of -0.81 (0.38) at Week 4 and -0.98 (0.22) at Week 12.
In the 180 mg cohort, maximum HBsAg decline of -1.94 log10 occurred at Week 4 in one subject (HBeAg negative). HBsAg declines continued beyond Week 12 for 2/3 subjects in the 180 mg cohort with available data, exceeding -1.00 log10 in both subjects. A 4th subject in the 180 mg cohort had continuous HBsAg decline up to 12 weeks post-dose, with a maximum decline of -0.73 log10 at Week 12 (the last available time point).
Mean log10 (SE) HBsAg decline in the 6 subjects in the 60 mg cohort (all HBeAg negative) was -0.24 (0.13) at Day 29. The maximum HBsAg decline in this cohort was -0.62 log10 at Day 29. Subjects in the 60 mg cohort will continue to be followed for twelve weeks. At this time only the four week data are available for the 60 mg cohort.
In chronic hepatitis B subjects administered 180 mg (N=4) or 60 mg (N=6) of AB-729 there were no SAEs. In the 180 mg cohort, 8 AEs were observed and included asymptomatic, transient Grade 1 ALT/AST in 1 subject, Grade 1 ALT only in 1 subject, and 1 subject with Grade 1 ALT /AST at baseline who experienced unrelated gastroenteritis and self-medicated associated with transient Grade 3 ALT/AST elevations. In the 60 mg cohort, 2 AEs were observed, and all subjects had normal ALT/AST levels.
Summary of clinical trial design
Study AB-729-001 is an ongoing first-in-human clinical trial of AB-729 consisting of three parts:
In Part 1, 3 cohorts of healthy subjects were randomized 4:2 to receive single doses (60mg, 180mg or 360mg) of AB-729 or placebo.
In Part 2, non-cirrhotic, HBeAg positive or negative, chronic hepatitis B subjects (N=6) currently taking nucleos(t)ide antiviral therapy with HBV DNA below the limit of quantitation received single doses (60mg or 180mg) of AB-729. All subjects continued their nucleos(t)ide antiviral therapy throughout the trial. Part 2 is designed to include dosing of AB-729 in HBV DNA positive chronic hepatitis B subjects.
In Part 3, chronic hepatitis B subjects, HBV DNA negative first and HBV DNA positive later, will receive multiple doses of AB-729 for up to six months.