Chronic hepatitis B virus infection affects about 16 million people in the United States and Western Europe. US Centers for Prevention and Prevention of Illness show that in the United States 2011-2012. There are about 847,000 non-institutionalized persons with chronic hepatitis B virus infection. Standard treatment for hepatitis B chronic infection is nucleotide / nucleoside analogues (NUC) administered daily as an oral dose or interferon injection regimen.
RNAi uses its own DNA sequencing gene to exclude or "silencing" the gene. This process has shown a promise as a limited therapy for people with chronic hepatitis B infection because it is capable of silencing viral hepatitis B viral RNA (mRNAs), resulting in the reduction of viral products such as active or chronic hepatitis B surface antigen (HBsAg).
The use of RNAi in clinical practice is limited by the safety concerns and the intravenous delivery method. ARO-HBV containing 2 minor RNA (siRNA) disorders, each of which is directly conjugated to N-acetylgalactosamine for delivery of hepatocytes and is designed to impress all mRNAs from covalently closed circular DNA (cccDNA) and the host of integrated viral DNA, without the need for additional delivery elements is delivered subcutaneously.
As such, investigators led by Edward Gane, MBChB, MD, FRACP, MNZM, a professor of medicine at Auckland University in New Zealand conducted phase 1 study, which "assesses the safety, tolerability and pharmacokinetic effects of single ascending ARO-HBV administration in normal healthy adult volunteers as well as the safety, tolerability and pharmacodynamic effects of multiple ascending doses of ARO-HBV in patients with chronic hepatitis B virus infection, according to clinical trials.
A total of 6 cohorts of normal healthy volunteers (4 active and 2 placebo) will receive subcutaneous doses of either 35 mg, 100 mg, 200 mg, 300 mg or 400 mg. "Chronic hepatitis B cohorts 2b-5b (n = 4, HBeAg pos or neg, NUC-treated or non-NUC) receive monthly doses of x 3 of 100 mg, 200 mg, 300 mg or 400 mg. Chorts of HBeAg pos, NUC – Naive and experienced chronic hepatitis B (groups of 8, 9 and n = 4) receive 300 mg monthly x 3. NUC-untreated receive NUC from the first day, "according to the study summary.
Preliminary data from the study showed that in healthy volunteers who received a single dose of ARO-HBV or placebo (n = 30) and patients with chronic hepatitis B who received 3 monthly doses of ARO-HBV in combination with entecavir or tenofovir over 6 weeks available HBsAg data (n = 24), single or multiple doses up to 400 mg were well tolerated. Furthermore, all patients with chronic hepatitis B infection had severe HBsAg responses (mean NADIR -1.9 Log10 [-98.7%], range -1.3 [-95.0%] to -3.8 Log10 [-99.98%]). In addition, patients in NUC (Group 8) and NUC-experienced patients (Group 9) had similar reductions in HBsAg (mean HBsAg decrease on day 57 for cohort 8 [n = 4] -1.7 Log10; means reducing HBsAg on day 57 for group 9 [n = 4] -1.9 Log10).
About 12% of all subcutaneous injections resulted in mild reactions at the injection site.
Bruce Given, Chief Operating Officer and Head of Research and Development at Arrowhead, talked about preliminary results in a statement by a pharmaceutical company, saying: "ARO-HBV continues to achieve a high level of activity [hepatitis B virus] types of patients in the AROHBV1001 study, and additionally the ARO-HBV tolerance profile supports its continuous development. "
Study "The first results with RNA interference (RNAi) in chronic hepatitis B (CHB) using ARO-HBV" was presented at the American Liver Loss Disease Association (AASLD), a liver meeting, from 9 to 13 November 2018 San Francisco, California.