Arbutus Reports Interim Multi-Dose Results from Phase II Clinical Trial of ARB-1467

[StephenCastlecrag]

Single Dose Data Demonstrate Significant Reduction in Serum HBsAg
Additive Reductions in Serum HBsAg Observed with Repeat Dosing over 3 Months
5 of 6 Patients in Cohort 1 Had Serum HBsAg Reductions of Greater Than 0.5 log10 After 3 Doses
Additional Multi-Dose ARB-1467 Data Expected in 4Q16
Company to Host Conference Call Today at 5 pm ET to Discuss Results

VANCOUVER, British Columbia and DOYLESTOWN, Pa., Sept. 29, 2016 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (ABUS), an industry-leading hepatitis B virus (HBV) therapeutic solutions company, today reported interim results from the first two cohorts of the ongoing ARB-1467 Phase II multi-dose clinical trial in chronically infected HBV patients.  The first two cohorts enrolled patients with hepatitis B e-antigen (HBeAg) negative chronic HBV infection. At this time, serum HBsAg data are available following single doses for both Cohort 1 and Cohort 2 and following multiple doses for Cohort 1.

Single dose ARB-1467 results for Cohorts 1 and 2 demonstrate significant reductions in serum HBsAg levels. Importantly, multiple dose results from Cohort 1 show a step-wise, additive reduction in serum HBsAg. These multiple dose results are the first of their kind for an RNAi product candidate in patients with chronic HBV infection. Treatment with ARB-1467 has been generally well tolerated to date.
         Single Dose HBsAg Reduction
(log10 IU/mL) Multiple Dose HBsAg Reduction
(log10 IU/mL)
Cohort N ARB-1467  
(mg/kg) Meana   Mean Maximumb   Maximumc   Meana   Mean Maximumb   Maximumc
1 6 0.2 -0.3 -0.4 -1.0 -0.6 -0.7 -1.3
2 6 0.4 -0.2 -0.3 -0.8 NA NA NA
Placebo   4d      0.0 0.0 -0.1 0.0 0.0 -0.1

aThe mean serum HBsAg reduction is the nadir value of the arithmetic mean of all values observed at each time point.
bThe mean maximum HBsAg reduction is the mean of each patient’s maximum reduction in serum HBsAg.
cMaximum HBsAg reduction is the best single reduction among all patients in a cohort.
dSingle dose placebo results are based on four subjects (two from each cohort). Multiple dose placebo results are based on the two placebo subjects in Cohort 1.

“The interim ARB-1467 data demonstrate significant serum HBsAg reduction following the first dose, which is enhanced with repeat dosing. This is a very important finding because it suggests that even greater reductions in serum HBsAg levels may be observed with continued dosing of ARB-1467,” said Dr. Douglas T. Dieterich, Professor of Medicine in the Division of Liver Disease at Icahn School of Medicine at Mount Sinai Medical Center. “These exciting data demonstrate the antiviral effect of ARB-1467 and the potential to include this agent as a component of a combination therapy regimen for the treatment of chronic HBV infection.”

“We are excited about these HBV efficacy data from our ongoing ARB-1467 Phase II trial demonstrating substantial reductions in serum HBsAg, which is an important first step towards one day curing chronic HBV infection. We believe that further study of ARB-1467 will help determine the optimal protocol to produce maximal reductions in serum HBsAg,” said Dr. Mark J. Murray, Arbutus’ President and CEO. “We plan to release additional multi-dose data later this year. We believe that ultimately curing HBV will require combination therapy and we are developing a portfolio of HBV assets with complementary mechanisms of action to accomplish this goal.”

ARB-1467 Phase 2 Trial Design
The Phase II trial is a multi-dose study in chronic HBV patients who are also receiving stable nucleot(s)ide analog therapy. The trial consists of three cohorts, each enrolling eight subjects; six receiving three monthly doses of ARB-1467, and two receiving placebo. The first two cohorts include HBeAg- patients, followed by a third cohort in HBeAg+ patients.

About ARB-1467
Arbutus’ RNAi candidate ARB-1467 comprises three RNAi triggers that target all four HBV transcripts, and has been shown in preclinical studies to reduce all viral antigen levels as well as cccDNA and HBV DNA.  ARB-1467 utilizes Arbutus’ proprietary lipid nanoparticle (LNP) platform, a clinically validated delivery technology which has been tested in hundreds of patients.

http://finance.yahoo.com/news/arbutus-reports-interim-multi-dose-200100353.html

[Liverpatient]

Very happy to recieve this good news folks. Encouraging, indeed, 0,5 log10 reduction of hbsag only after three months of low doses is encouraging. Can't wait to learn their next multi-dose, eventually elevated dose results before the end of this year:))

[StephenCastlecrag]

I understand that their RNAi again targeted the 4 viral antigens, very much like ARC 520. I still wish they can designed RNAi that targets the core and X protein.

[studyforhope]

Do you mean iRNA contructs that have higher efficacy against core and x transcription than the current iRNAs?

the problem with inhibiting core synthesis is that very little core is needed to synthesize virions. The x protein is already synthesized in minute amounts only.
It is not possible to measure these viral antigens in human subjects as a result of the iRNA treatment. One can measure hbsag and in e ag pos the e antigen.

[studyforhope]

They used only e neg patients. Their hbsag reduction results are similar to the arrowhead 520 results, multiple dosing was a little better.
they are at least fully aware that this interference treatment can only be expected to work as a component in a combo therapy.
arrowhead 521 will be very interesting, will they indeed be able to reach 2 log reductions with it as was the case with the chimps?

[sorte]

studyforhope: how that combo gonna look ? nucs than + arc 520/521 than peginf ? Or sth else ?

[studyforhope]

Arbutus has their own core assembly inhibitor and are preparing combo trials with that. See the Arbutus aasld abstract. Other than that they will envision combos with nucs and ifn.