Chronic hepatitis B virus infection affects approximately 16 million people in the United States and Western Europe.American centers for disease control and prevention estimate that in 2011-2012 about 847,000 non- institutionalized individuals with chronic hepatitis B infection in the United States The standard treatment for chronic hepatitis B virus infection is nucleotide / nucleoside analogues (NUCs) administered daily as an oral dose or as an interferon injection regimen. 19659002] RNAi uses the gene's own DNA sequence to disable or "silen" the gene. proved promising as a limited therapy for individuals with chronic hepatitis B virus infection because it is capable of silencing hepatitis B virus messenger RNA (mRNA), 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 safety concerns and the intravenous administration method. ARO-HBV, which includes 2 small interfering RNAs (siRNAs), each directly conjugated with N-acetyl galactosamine to release hepatocytes and designed to remove all mRNA from covalently closed circular DNA (cccDNA) and extinguishing host-integrated viral DNA without the need for additional delivery elements is delivered subcutaneously.
As such, researchers led by Edward Gane, MBChB, MD, FRACP, MNZM, a professor of medicine at the University of Auckland, in New Zealand, lead a phase 1/2 study, "evaluating safety , tolerability and pharmacokinetic effects of single ARO-HBV doses in normal healthy adult volunteers, as well as the safety, tolerability and pharmacodynamic effects of multiple escalating doses of ARO-HBV in patients with chronic hepatitis B virus infection, "according to the clinical study information .
A total of 6 cohorts of normal healthy volunteers (4 active and 2 placebo) receive a subcutaneous dose 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 not on NUCs) receive monthly doses x 3 of 100 mg, 200 mg, 300 mg or 400 mg. of HBeAg pos, NUC-naïve and experienced chronic hepatitis B (cohorts 8, 9, n = 4 each, respectively) received 300 mg per month x 3. NUC-untreated NUCs received from day 1, "according to the study resume.
Preliminary data from the study indicate that in healthy volunteers receiving a single dose of ARO-HBV or placebo (n = 30) and patients with chronic hepatitis B receiving 3 monthly doses of ARO-HBV in combination with entecavir or tenofovir with more than 6 weeks of available HBsAg data (n = 24), the single or multiple doses up to 400 mg were well tolerated. In addition, all patients with chronic hepatitis B virus infection had strong HBsAg responses (mean 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 NUC-experienced patients (cohort 9) saw similar HBsAg reductions (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).
Approximately 12% of all total subcutaneous injections resulted in mild reactions at the injection site.
Bruce Given, MD, chief operating officer and chief research & development at Arrowhead spoke about the preliminary results in a statement from the pharmaceutical company, saying: "ARO-HBV continues to achieve high levels of activity in all [hepatitis B virus] patient types in the AROHBV1001 study and in addition the tolerability profile of ARO-HBV supports its continuation development. "
The study," First results with RNA interference (RNAi) in chronic hepatitis B (CHB) using ARO-HBV "was presented at the 2018 American Association for the Study of Liver Diseases ( AASLD ) Liver Meeting, November 9-13, 2018, in San Francisco, California.