Chronic hepatitis B virus infection affects around 16 million people in the United States and Western Europe. The US Center for Disease Control and Prevention estimates show that there were around 847,000 people who were not internalized with chronic hepatitis B virus infection in the United States in 2011-2012. The standard treatment for chronic hepatitis B virus infection is a nucleotide / nucleoside (NUC) analogue that is given daily as an oral dose, or an interferon injection regimen.
RNAi uses its own gene DNA sequence to turn off or "silence" genes. This process has shown promise as limited therapy for individuals with chronic hepatitis B virus infection because it is able to silence the virus carrying the hepatitis B virus (mRNA), resulting in a reduction in viral products, such as active or chronic hepatitis B surface antigens (HBsAg).
The use of RNAi in clinical practice has been limited by safety problems and intravenous delivery methods. ARO-HBV, which consists of 2 small mixed RNAs (siRNAs), each of which is directly conjugated to N-acetyl galactosamine to encourage the delivery of hepatocytes and is designed to silence all mRNAs from closed covalent circular DNA (cccDNA) and host-integrated DNA virus , without the need for additional shipping elements sent subcutaneously.
Thus, researchers led by Edward Gane, MBChB, MD, FRACP, MNZM, a professor of medicine at the University of Auckland, in New Zealand, led a phase 1/2 study, which "evaluates the safety, tolerability, and single pharmacokinetic effects of increased ARO-HBV doses in normal healthy adult volunteers, as well as the safety, tolerability, and pharmacodynamic effects of some elevated ARO-HBV in patients with chronic hepatitis B virus infection, "according to clinical trial information.
A total of 6 normal healthy volunteer cohorts (4 active and 2 placebo) will receive subcutaneous doses of either 35mg, 100mg, 200mg, 300mg, or 400mg. "Chronic hepatitis B cohort 2b-5b (n = 4, HBeAg postal or neg, NUC-treated or not on NUCs) received a monthly dose of x 3 from 100 mg, 200 mg, 300 mg or 400 mg. Cohort of HBeAg post, NUC-naïve and having chronic hepatitis B (cohort 8, 9 each, n = 4 each) received 300 mg per month x 3. The untreated NUC received NUC from day 1, "according to an abstract study.
Preliminary data from this study show 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 with greater than 6 weeks of available HBsAg data (n = 24), single or multiple doses up to 400 mg can be well tolerated. Furthermore, all patients with chronic hepatitis B virus infection had strong HBsAg responses (average NADIR -1.9 Log10 [-98.7%], range -1.3 [-95.0%] to -3.8 Log10 [-99.98%]) In addition, NUC-naïve patients (cohort 8) and patients who experienced NUC (cohort 9) saw the same HBsAg reduction (mean HBsAg reduction on day 57 for cohort 8). [n = 4] -1.7 Log10; HBsAg reduction at 57 days for cohort 9 [n = 4] -1.9 Log10).
About 12% of total subcutaneous injections produce a mild injection site reaction.
Bruce Given, MD, chief operating officer and head of research & development at Arrowhead talked about preliminary results in a statement by a pharmaceutical company, said, "ARO-HBV continues to achieve high levels of activity in all [hepatitis B virus] type of patient in the AROHBV1001 study and, additionally, the tolerability profile of ARO-HBV supports its ongoing development. "
Research, "First Results with RNA Interference (RNAi) in Chronic Hepatitis B (CHB) Using ARO-HBV," was presented at the Liver Liver Health Association (AASLD) in 2018, November 9-13, 2018, in San Francisco, California .