Chronic hepatitis B virus infection affects approximately 16 million people in the United States and Western Europe. The Centers for Disease Control and Prevention (CDC) shows that there are approximately 847,000 unregistered people with chronic hepatitis B virus infection in the United States in 2011-2012. The standard treatment for chronic hepatitis B virus infection is the administration of daily oral doses of nucleoside / nucleoside analogs (NUCs) or interferon injections.
RNAi uses the DNA sequence of the gene itself to turn off or "silence" the gene. This process is promulgated as a limited treatment for chronic hepatitis B virus infections because it can reduce viral products such as chronic hepatitis B surface antigen by inhibiting hepatitis B virus messenger RNA (mRNA).
The use of RNAi in clinical practice has been limited by safety concerns and intravenous delivery methods. (SiRNA) directly conjugated to N-acetylgalactosamine to induce hepatocyte delivery, and all mRNAs from covalently-closed circular DNA (cccDNA) and host-integrated virus DNA need to be silenced ARO-HBV Additional delivery elements designed to deliver are delivered subcutaneously.
Professor Edward Gane, MD, FRACP, MNZM of the University of Auckland, New Zealand said, "We evaluated safety and tolerability and found that the safety of multiple uptake of ARO-HBV in patients with chronic hepatitis B virus infection , A single rising dose of pharmacokinetic and pharmacokinetic effects as well as a single elevated dose of ARO-HBV in normal healthy adult volunteers.
A total of six healthy healthy volunteers (four active and two placebo) will receive a subcutaneous dose of 35 mg, 100 mg, 200 mg, 300 mg or 400 mg. "The chronic hepatitis B cohort 2b-5b (n = 4, HBeAg pos or neg, treated with NUC or excluded from NUC) receives a monthly dose of 100 mg, 200 mg, 300 mg or 400 mg x 3. HBeAg pos, According to the Abstract, chronic hepatitis B (8, 9, and n = 4, respectively), aged and experienced, is 300 mg x 3 per month. 3. People who do not receive NUC treatment receive NUC from day 1.
According to preliminary data from this study, patients with chronic hepatitis B who received ARO-HBV or placebo (n = 30) in a single dose and entecavir or tenofovir for three months with ARO- Six weeks (n = 24), up to 400 mg of single or multiple doses were well tolerated. In addition, all patients with chronic hepatitis B infection had a strong HBsAg response (mean NADIR -1.9 Log10 [-98.7%], Range -1.3 [-95.0%] ~ 3.8 Log10 [-99.98%]). In addition, patients without NUC compliance (cohort 8) and patients with NUC (cohort 9) showed similar HBsAg reductions (mean 57 days HBsAg reduction on day 8 of cohort [n = 4] -1.7 Log10; HBsAg reduction at day 57 on day 9 of cohort [n = 4] -1.9 Log10).
Approximately 12% of all total subcutaneous injections resulted in a mild injection site reaction.
Arrowhead's chief operating officer and research director Bruce Given said in a statement from the pharmaceutical company, "ARO-HBV continues to be a high-level activity for everyone. [hepatitis B virus] Patient types were included in the AROHBV1001 study, and the ARO-HBV tolerability profile supports continued development. "
The study is the first outcome of "Chronic Hepatitis B Hepatitis B RNAi Intervention (RNAi) using ARO-HBV" at the American Liver Disease Society (AASLD) meeting in 2018, November 9-13, 2018, San Francisco, California.