Since NM283 is very new, I don't believe anyone here has any experience
with it. But please keep us updated about your progress, it would be
great to get first-hand news.

The effects of interferon are well known to most here, though.
Once-weekly shots means Peg-Intron or Pegasys, with the usual sides of
flu-like symptoms, fatigue, and assorted other goodies. But without the
ribavirin, you may have a smoother sailing.

Thomas

From reading about Valo<whatever>, it seems to be a more focussed drug
in terms of HCV - Ribavirin is,  chemically, a more brute force method.

My experience with anti-HIV drugs is that they all have radically
different side-effects.  I'm sure that there are a lot of people here
who would be very interested in hearing about the side-effects that you
experience (hopefully less than Riba) and how it affects your blood
levels.

It's not clear why the interferon/riba combo works.  The assumption is
that the riba reduces the viral activity and ramping up the immune
system gets the rest.  The assumption is that the riba can be replaced
by other drugs that suppress the virus with fewer side-effects.  
Hopefully that's the case.

Please stick around and keep us up to date with how it works!

Gordo

Hey Mark, this is exciting news for us!  I'll spend some time tomorrow
searching for some no-too-technical info on valacitabine, and post links.

Best to you,
Kathy

No suggestions but good luck with the treatment. There are pro's and con's
too being part of a  "Trial"
pro is they are cheap (really cheap)
con is they are very regimented  hope you don't get the placebo!
pro is if we didn't have trials we would all lose out on what works and what
doesn't!

Ask Mags about regimented, she may be pulled off  a trial cause she cant
take procrit or neupogen. Most of in here know that sooner or later you'll
have to take one or both before treatment is over.

Kill the dragon   Buster

the place of ribavirin. >The trial is once a week interferon and twice

NM283...Any thoughts, concerns, >suggestions, or personal experiences you
would

Hi all:
Here is a news article (heavily edited by me) from last may.  Note that
this study is sponsored by Idenix (makers of NM 283 = valopicitabine) on
previously untreated genotype 1 heppers, using Pegintron, and their second
phase II study will be larger and use Pegasys.  It doesn't look like the
same study Mark will be in.  Also note that this next study will only run
24 weeks, and one of the 3 tx groups will be restricted to valopicitabine
monotherapy, one to NM283 plus Ifn combo, and one to the combo plus
ribavirin (ugh).  I don't see a classical ‘placebo' group that gets sugar
pills.  The entire article can be had here:
http://www.hepatitisneighborhood.com/

There are also a couple of relevant new (technical) summaries about NM283
at this site:
http://www.hcvadvocate.org/news/reports/AASLD_2005/TOC_AASLD_2005_HCV.htm

And recent articles on the status of experimental HCV treatments:
http://www.hivandhepatitis.com/hep_c/news/2005/ad/102605_a.html

http://www.ebar.com/news/article.php?sec=news&article=389

Q: to Mark: How long will your tx last?

Snowy here.
Kathy

Experimental Drug Combo Tested in Tough-to-Treat Patients
John C. Martin  04-27-05

..Doctors in an ongoing Phase 2 clinical trial are testing the
combination of valopicitabine (also known by its code name NM283—along
with peginterferon alfa-2b (PEG-Intron/Schering-Plough) in a group of
patients with the genotype 1 strain of the virus.

Valopicitabine is an oral nucleoside analog that works by inhibiting an
enzyme that HCV uses to make copies of itself.

Thirty patients were enrolled in the study, and thus far, nine of them
have completed 24 weeks of therapy [...] the patients taking combination
therapy have achieved an average reduction in blood levels of HCV RNA by
nearly 100 percent...The patients have never been treated before for
hepatitis C, and are infected with the genotype 1 strain of the virus.

"This is the first time that we are seeing 24-week data for an antiviral
drug directly targeting a specific enzyme of the hepatitis C virus," said
Afdhal, who is also chief of Hepatology at Beth Israel Deaconess Medical
Center in Boston. "These preliminary data are promising, and suggest that
direct antiviral drugs, such as valopicitabine, could set a new treatment
standard in hepatitis C by offering hepatitis C patients—particularly
patients infected with HCV genotype 1—potentially improved clinical
benefit with fewer side effects." No serious adverse events have surfaced
in the trial so far, according to Nefdhal's team.

The investigators have also found that those in the combination group had
better responses to treatment than those taking valopicitabine alone.
Those taking valopicitabine and peginterferon alfa-2b at 12 weeks had
reductions in viral load, on average, of 99.99% compared to an 86.5%
reduction in the group taking valopicitabine alone.

"We are very encouraged by the 24-week antiviral effect reported in
patients receiving the combination of valopicitabine and pegylated
interferon even though this trial was designed as a drug-drug interaction
trial and not to maximize the potential therapeutic response in
patients... "We have designed the phase 2b trials to optimize potential
outcomes of the combination treatment and we will be able to evaluate the
full potential of valopicitabine from these trials."

Idenix initially launched this trial with the smaller number of patients
to determine whether there were any drug-to-drug interactions between
valopicitabine and pegylated interferon. They didn't expect to see the
positive results that followed. "Subsequently, due to the encouraging
hepatitis C RNA reductions observed in most patients during the first
weeks of the trial in the combination arm," the study was extended, said
Jean-Pierre Sommadossi, PhD, Chairman and CEO of Idenix, in a recent
conference call to investors.

Idenix is sponsoring a second phase 2 trial to test the combination of
valopicitabine and peginterferon alfa-2a (Pegasys/Hoffman LaRoche)
compared to standard care in a group of 171 patients with the genotype 1
strain of HCV. There will be three treatment groups in this 24-week trial:
valopicitabine monotherapy, valopicitabine plus peginterferon alfa-2a, or
peginterferon alfa-2a plus the antiviral medication, ribavirin. Patient
enrollment is expected to conclude this summer.  

In the meantime, Brown said the next step will be to determine if the
patients achieve sustained virological responses (SVR), defined as
undetectable viral levels for a minimum of 6 months after treatment ends.

A thought came to mind immediately when reading your post.  Be carefull
that if you do get a side effect of vomiting that you do not dehydrate.
I can't remember (and maybe someone could help me) if it is the
ribavarin or the interferon that causes dehydration. If it is the
interferon and you have another drug that may dehydrate you I would be
careful. Always have a drink available (non alcoholic lol). I also used
pedialite for hydration.

best of luck to you,
Mary Ann

A bit more from the AASLD Conference:

"Valopicitabine Plus Peginterferon Alfa-2a Highly Effective at
Suppressing HCV in Peginterferon Plus Ribavirin Nonresponders

Interim results of randomized, open-label, multicenter, phase 2b trial
Summary of Key Conclusions
Valopicitabine plus peginterferon alfa-2a demonstrated significantly
greater anti-HCV activity than retreatment with peginterferon plus
ribavirin in nonresponders with chronic hepatitis C
Antiviral efficacy of valopicitabine plus peginterferon related to
valopicitabine dose
67% of patients receiving valopicitabine (800 mg/day) plus peginterferon
achieved > 2-log10 decline in HCV RNA after 12 weeks of treatment
Overall acceptable safety and tolerability
Gastrointestinal symptoms more common with valopicitabine treatment
No viral breakthrough or valopicitabine resistance detected"

A lot more data at
http://clinicaloptions.com/Hepatitis/Conference%20Coverage/San%20
Francisco%202005/Capsules/95.aspx?Track=HCV%20Management
%20Facing%20New%20Challenges
(note: you have to re-assemble all three lines for the complete URL)

Or go to http://clinicaloptions.com/Hepatitis.aspx and select "HCV
Management..." under "CCO Independent Conference Coverage", and look for
the Valopicitabine title above.

This site requires free registration.

Thomas