Arrowhead Pharmaceuticals Presents Late-Breaking Preliminary Clinical Data on ARO-HBV at Liver Meeting® 2018
- Mean HBsAg reduction of -1.9 Log10 (-98.7%) with a range of -1.3 Log10 (-95.0%) to -3.8 Log10 (-99.98%)
- ARO-HBV appears to be well-tolerated at monthly doses up to 400 mg
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Initial results from normal healthy volunteers (NHV) who received a single dose of ARO-HBV or placebo (n=30) and chronic hepatitis B patients who received three monthly doses of ARO-HBV in combination with entecavir or tenofovir (NUC) with greater than six weeks of available hepatitis B surface antigen (HBsAg) data (n=24) include the following:
ARO-HBV administered subcutaneously appears to be well-tolerated at
single or multiple monthly doses up to 400 mg
- Mild injection site reactions were observed with approximately 12% of subcutaneous injections
Strong HBsAg responses were observed in all HBV patients
- Mean NADIR -1.9 Log10 (-98.7%)
- Range -1.3 (-95.0%) to -3.8 Log10 (-99.98%)
HBsAg reductions were similar in hepatitis B e-antigen (HBeAg)
positive and HBeAg negative patients
- Mean HBsAg NADIR in HBeAg positive (n=11) -2.1 Log10
- Mean HBsAg NADIR in HBeAg negative (n=13) -1.8 Log10
HBsAg reductions were similar for NUC naïve patients (cohort 8) and
NUC experienced patients (cohort 9)
- Mean HBsAg reduction on day 57 for cohort 8 (n=4) -1.7 Log10
- Mean HBsAg reduction on day 57 for cohort 9 (n=4) -1.9 Log10
- This study highlighted an improvement over results with Arrowhead’s first-generation compound ARC-520, which targeted only HBV transcripts derived from cccDNA (Wooddell, 2017)
- HBsAg responses observed with ARO-HBV are consistent with the ability of ARO-HBV to silence HBV mRNA from cccDNA and host-integrated viral DNA, a major source of HBsAg in certain patient populations (Wooddell, 2018)
- Responses were also observed in all other virologic parameters (HBV DNA, HBV RNA, HBeAg, HBcrAg)
“ARO-HBV continues to achieve high levels of activity across all HBV
patient types in the AROHBV1001 study and, additionally, ARO-HBV’s
tolerability profile supports its continued development,” said
First Results with RNA interference (RNAi) in Chronic Hepatitis B (CHB) Using ARO-HBV
- Publication Number: LB-25
- Session: Late-Breaking Poster Session
Session Date and Time:
November 12, 2018from 8:00 AM to 5:30 PM PT
Moscone Center North/South Building, Hall C
Edward J. Gane, et al.
A copy of the poster may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.
AROHBV1001 (NCT03365947) is a Phase 1/2 clinical study evaluating the safety, tolerability, and pharmacokinetic effects of single-ascending doses (SAD) of ARO-HBV in healthy adult volunteers, as well as the safety, tolerability, and pharmacodynamic effects of multiple-ascending doses (MAD) of ARO-HBV in patients with chronic HBV.
Dosing in the SAD portion of the study is complete and included five cohorts at dose levels of 35, 100, 200, 300, and 400 mg. Dosing in the MAD portion of the study is ongoing and includes cohorts receiving three monthly subcutaneous injections of ARO-HBV at doses of 25, 50, 100, 200, 300, and 400 mg. The 25 and 50 mg dose cohorts were recently added, and cohort sizes were increased to n=8 in the dose escalation HBV patient cohorts to better characterize ARO-HBV dose response. The study is also evaluating whether there is added effect with weekly or bi-weekly loading doses. AROHBV1001 is designed to enroll 30 healthy volunteers and up to 72 HBV patients.
This interim analysis reports on all single dose NHV cohorts and initial
CHB cohorts that received monthly doses of ARO-HBV and had greater than
6 weeks of HBsAg assay results. For CHB, viral DNA (Roche Cobas, LLOQ 20
IU/mL), viral RNA (Abbott m2000, LLOQ 1.65 Log U/mL, Butler 2018) and
antigens (qHBsAg (Roche Elecsys, LLOQ 0.05 IU/mL), qHBeAg (
Here we report on safety and tolerability in all NHV and safety, tolerability and virologic assessments in CHB cohorts 2b-5b, 8 and 9. Cohorts 2b-5b were HBeAg positive or negative, NUC naïve or NUC experienced at baseline, and cohorts 8 and 9 were HBeAg positive, treatment naïve or NUC experienced, respectively. NUC experienced patients continued their daily NUC throughout the study and NUC naïve CHB patients started daily NUC on day 1.
Single dose PK in NHV will be reported elsewhere. Virologic results reported are through 56 days after 3rd dose (day 113) when available or most recent.
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Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
Investors and Media:
LifeSci Advisors, LLC