- ARB-1467 Reduces Serum HBsAg in Both HBeAg Negative and HBeAg Positive Patients
- Results of Biweekly Dosing from Cohort 4 Expected in 3Q17
- Additional Study Starting in 2H17 to Evaluate Longer Term Dosing with Immune Modulatory Agents
VANCOUVER, Canada and WARMINSTER, PA, USA I April 22, 2017 I Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading Hepatitis B Virus (HBV) therapeutic solutions company, presented results of the first three cohorts of a Phase II study of its RNAi agent, ARB-1467, at the European Association for the Study of the Liver (EASL) in Amsterdam, The Netherlands.
“We are very pleased to present updated Phase II results for ARB-1467 that show a consistent reduction in HBsAg in HBV patients regardless of HBeAg status with a favorable safety profile. We look forward to a 3Q17 announcement of the results of Cohort 4, which is evaluating five bi-weekly doses of ARB-1467 with extended monthly dosing out to one year for patients who meet predefined response criteria,” said Dr. Mark J. Murray, Arbutus’ President and CEO. “Furthermore, we are planning to initiate a new study of ARB-1467 in 2H17 to evaluate longer dosing of ARB-1467 combined with immunomodulatory agent. We believe that this study could pave the way for Phase IIb studies while we continue to advance the rest of our pipeline to enable new treatment regimens for further improvement in clinical outcomes.”
The presentation is titled “A Phase 2a Study Evaluating the Multi-Dose Activity of ARB-1467 in HBeAg Positive and Negative Virally Suppressed Subjects with Hepatitis B”, and a copy of the poster can be accessed by visiting the Investor section of www.arbutusbio.com and selecting ‘Events and Presentations.’
| Cohort | ARB-1467 (mg/kg) |
HBeAg | Single Dose HBsAg Reduction (log10 IU/mL) |
Multiple Dose HBsAg Reduction (log10 IU/mL) |
||||||||
| N | Meana | Mean Maxb |
Maxc | N | Meana | Mean Maxb |
Maxc | >0.5 logd | >1.0 logd | |||
| 1 | 0.2 | Neg | 6 | -0.3 | -0.4 | -1.0 | 6 | -0.6 | -0.7 | -1.3 | 5 | 1 |
| 2 | 0.4 | Neg | 6 | -0.2 | -0.3 | -0.8 | 5e | -0.8 | -0.9 | -1.1 | 4 | 3 |
| 3 | 0.4 | Pos | 6 | -0.2 | -0.3 | -0.6 | 6 | -0.7 | -0.8 | -1.6 | 4 | 2 |
| Placebo | All | 6f | 0.0 | 0.0 | -0.1 | 6 | 0.0 | -0.1 | -0.1 | 0 | 0 | |
a The mean serum HBsAg reduction is the nadir value of the arithmetic mean of all values observed at each time point.
b The mean maximum HBsAg reduction is the mean of each patient’s maximum reduction in serum HBsAg.
c Maximum HBsAg reduction is the best single reduction among all patients in a cohort.
d Number of patients reaching this threshold
e Multiple dose results in Cohort 2 exclude one patient that discounted at day 36 due to an acute hepatitis E virus (HEV) super-infection
f Placebo results are based on six subjects (two from each cohort).
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 four cohorts, the first three of which enrolled eight subjects each (six receiving three monthly doses of ARB-1467 and two receiving placebo) and the fourth is enrolling twelve patients (all of whom will receive 5 bi-weekly doses of ARB-1467). Cohorts 1, 2, and 4 include HBeAg- patients and Cohort 3 included HBeAg+ patients. The protocol for Cohort 4 allows for dosing to be extended to up to one year of ARB-1467 dosing for patients who meet predefined response criteria.
Next Steps for ARB-1467
In addition to the ongoing Phase 2 Cohort 4, Arbutus will initiate a new study in 2H17 to study longer term dosing of ARB-1467 in combination with nucleot(s)ide analog therapy as well as pegylated interferon or another immune modulator. This study will explore the possibility of driving HBsAg to very low, if not undetectable, levels with ARB-1467 along with an immune modulating mechanism. While this study may include pegylated interferon as the immune boosting component that could lead to later stage development, Arbutus also plans to evaluate other immunomodulatory approaches, such as its proprietary checkpoint inhibitor program, in future combination studies. Arbutus’ core protein/capsid inhibitor AB-423, which is being evaluated for monotherapy safety and activity in 2017, will be ready to be included in studies with RNAi and approved agents in 2018. ARB-1740, a next generation RNAi agent, is being evaluated in an ongoing multi-dosing study in HBV patients, the results of which will be announced in 2H17 to enable a potency comparison between ARB-1467 and ARB-1740.
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.
About Arbutus
Arbutus Biopharma Corporation is a biopharmaceutical company dedicated to discovering, developing and commercializing a cure for patients suffering from chronic HBV infection. Arbutus is headquartered in Vancouver, BC, and has facilities in Warminster, PA. For more information, visit www.arbutusbio.com.
SOURCE: Arbutus Biopharma
