
BILN 2061 could mark the beginning of the end for HCV
This is a duplicate post for those who do not frequent
alt.hepatitis-c. Sorry for the redundancy for those who do, and
aren't interested.
I've been following this exciting story since 1996 when I first read
that vertex had mapped the structure of the HCV NS3 protease, an
enzyme essential for HVC replication.
Last year the NATAP reported a breakthrough potential treatment of
Hepatitis C, called BILN 2061 which "stunned" the scientific
community. Scientist had been attempting to create similar {*filter*}
without success since 1996 when the structure of the NS3 protease was
first discovered. This new orally available drug focuses on the
NS3/4A protease, which is essential for HCV replication. BILN
inhibits the NS3 enzyme and thus inhibits replication of the virus.
The drug can reduce (3 log or 1000-fold decrease) the virus in "ALL"
subjects in an astonishing 48 hours, something that can take up to 24
weeks to occur in those taking the conventional pegalys or
pegintron-and only about 50% of the population will respond to these
treatments at all). If you don't know, 3 log is the same as 10 raised
to the power of 3 (10^3 or 1000). So, if your viral load is 1
million-10^6 and you had a 3 log (10^3) decrease, your viral load
would drop to 1000. With most test, less than 100 copies is
considered undetectable. Again, this decrease occurs in just 48 hours
with BILN. At this preliminary time there have been no published
trials lasting over 48 hours.
Not only do these protease inhibitors work fast and are orally
available, but the great news for those who have suffered through the
intolerable misery of interferon there have been no observed side
effects from BILN.
The best news about BILN may have come in April 2003 when researchers
discovered that the NS3 protease had a far greater roll than just
viral replication. They found that the NS3 protease was the reason
that people contracting HCV could not fight the virus off themselves,
similar to how the body eliminates a flu virus. The NS3 protease
effectively interferes with the body's immune system, preventing the
body from clearing the virus on its own. With BILN's ability to
reduce the NS3 protease the body's immune system is effectively
restored and able to fight the remaining virus
So, BILN works on two fronts to eliminate the HCV. It prevents
replication of the virus and it re-instates the body's own defense
mechanism by preventing interference of the NS3 on the immune system
and allowing the body to clear the virus on its own.
Also, the implications of the discovery of BILN are far reaching in
the competitive pharmaceutical industry. If nothing else BILN has
jump started a race that nearly did not happen, given that some
scientist were fearful as early as last year that such a medication
might be impossible to produce. BILN was the shot heard around the
pharmaceutical world, leaving companies scrambling to come up with
similar medications.
The optimism about BILN is a little tempered when it is realized that
it is only in phase II of its development and will probably not be
available for several years. There is also a chance that the drug may
never come to market at all, given all the things that can go wrong
during a trial (the good news about this is that there are several
other candidate {*filter*}, by this company as well as other companies,
that are currently in the pipeline. Also, since viruses mutate so
quickly, there is always a chance of drug resistance, but the good
news here is the drug works so quickly that resistance might not be
much of a problem. This drug will probably be combined with other
{*filter*} to produce a timely and optimal response.
Timeline:
Discover of the HCV NS3 protease:
http://www.***.com/
Discovery of BILN 2061 which interferes with NS3:
http://www.***.com/
Discover of NS3 interference with immune system and HCV persistence:
http://www.***.com/
BTW, this is my first (and probably last) post. Reading slanderous
posts and negative talk about HCV are not my favorite pastimes.
Best wishes to all,
Bret