—Christine. M. Kukka, Project Manager, HBV Advocate
A ground-breaking approach to hepatitis B treatment,
which manipulates RNA messengers to halt viral replication, has begun
its first human clinical trial. If successful, this approach would be a
paradigm shift in treatment, possibly replacing interferon and
antivirals.
In animal trials, reported in the May 2013 journal Molecular Therapy,
RNA interference (RNAi) treatment reduced hepatitis B surface antigen
(HBsAg) levels to undetectable within 24 hours in mice and the antigen
remained undetectable for nearly a month.
RNAi treatment works by
destroying or "silenc-ing" the molecular messengers that carry
important genetic information to the hepatitis B virus (HBV)
antigen/protein factories. Without the critical information that
messenger RNA molecules carry, these antigen factories shut down and
HBV reproduction declines dramatically.
Early RNAi research found that
RNA silencing worked extremely well in the liver, but the challenge has
been to create a formula and delivery system to target hepatitis B
antigens in liver cells without affecting other important cells.
Arrowhead Research Corp. found
that when the small RNA interrupters are linked to cholesterol, they
target liver cells extremely well, and the addition of special polymers
helps the gene-silencing process. Arrowhead designed an intravenous
formula, called ARC-520, that is utilized in its Phase 1 trial.
The hope is that when the viral
load is dramatically reduced, the body's immune system can gain the
upper hand and eradicate the infection on its own.
In addition to its mouse trial, a
similar trial involving an HBV-infected chimp with an extremely high
viral load also led to rapid reduction in HBV DNA and a 90% reduction
in another hepatitis B antigen—the hepatitis B "e" antigen (HBeAg).
The clinical trial of ARC-520
(which uses a Dynamic Polyconjugate delivery platform and includes two
distinct RNA silencing agents that should shut down hepatitis B antigen
reproduction) in humans is taking place in Melbourne, Australia. It is
a randomized, double-blind, placebo-controlled trial. Each group of
six healthy volunteers will receive either a placebo intravenous
injection or a single dose of ARC-520.
The study, which concludes this
fall, assesses the treatment's dosing safety and effectiveness. A
Phase 2 trial involving people infected with HBV is scheduled to start
in 2014 IN HONG KONG.
Labels: ARC-520, drugs in development, RNAi