— Christine M. Kukka, Project Manager, HBV Advocate
For months, the hepatitis B community has
been waiting for updates about the experimental drug REP 9AC that stops
production of hepatitis B surface antigen (HBsAg) within weeks. There
will be no news unveiled at this week's international Liver Conference
in Washington D.C., but a new clinical trial is about to begin that
combines REP 9AC with an immune stimulant and an antiviral.
REP 9AC, administered
intravenously, uses nucleic acid-based polymers to stop HBV-infected
liver cells from releasing HBsAg—an antigen critical to the production
of HBV. Early clinical trials in HBV-infected animals and humans showed
that within four weeks REP 9AC rapidly reduced or eliminated HBsAg in
The drug’s developers,
REPLICor Inc. based in Montreal, had hoped the dramatic decline in HBsAg
would enable the immune system to quickly gain the upper hand and
eradicate the infection. However, patients treated with just REP 9AC
didn’t clear the infection as anticipated. Despite the decline in HBsAg,
in many cases viral load remained detectable and the infection remained
entrenched in liver cells.
“In some patients, REP 9AC
(by itself) was enough to allow their immune systems to fully recover
during the course of about six months of treatment and these patients
have long-term control (after four years) of their infection,” Andrew
Vaillant, REPLICor’s chief scientific officer and director of
operations, wrote in an email to HBVAdvocate.org
. Next, developers
tweaked the drug to allow it to be absorbed more easily (the
second-generation drug is called REP 9AC’) and tried adding either
pegylated interferon (Pegasys) or another immune stimulator, thymalfasin
to the ongoing REP 9AC’ treatment to see if the drug combination would
knock out the infection.
At the July 2013 meeting of
the Asian Pacific Association for the Study of Liver Disease,
researchers reported that the number of surface antibodies did rise
rapidly in these patients and viral load continued to decline even after
treatment ended, but they still were not happy with the result.
In its latest clinical
trial, involving 20 patients, researchers will try a triple treatment of
REP 9AC’, the immune stimulant and an antiviral (either entecavir
(Baraclude) or tenofovir (Viread). “This triple combination will likely
provide the most potent response in patients,” Vaillant wrote.
Many patients have been
frustrated with the slow pace of REPLICor’s drug development. The
company is privately-held and its development pace is so far slower than
that of “big pharma companies” that are funded through publicly-traded
“We are aware that some
patients have been frustrated with the apparent ‘slow’ pace of progress
with this technology,” Vaillant told the HBVadvocate, “but we have had
to do many things with these initial proof of concept experiments,
including optimizing the dosing regimen and tolerability for REP 9AC/REP
9AC’ and understanding how best to use REP 9AC’ in a combination
regimen to achieve the best possible sustained viral response result in
patients with a defined course of therapy.
“We feel that we are
getting to the end of this process and we are hopeful that the European
study will be the last confirmatory piece of evidence we will need to
start the registration process for this treatment,” he wrote.
Labels: drugs in development, REP 9AC'