Potential treatment without Interferon

[DragonSlayer45]

This is a report that came out of the AASLD today. Some of you had heard of this before where they did a first of a kind trial using only a polymerase inhibitor and a protease inhibitor. There was no interferon or ribavarin in htis trial. It seems to have some promise. It is way early to say anything conclusive about this but encouraging just the same. This may be a glimpse of the future. below is the news bulletin.

Presented: Tuesday, November 3, 2009, 8:00 am Eastern Time in Boston, MA




ALEXANDRIA, Va. and BOSTON, Nov. 2 /PRNewswire/ -- All approved therapy
regimens to treat patients with hepatitis C are based on interferon, which
must be injected. In this clinical trial to be presented at the annual meeting
of the American Association for the Study of Liver Diseases, researchers
treated patients - both treatment naive and experienced patients - with a
twice daily oral combination therapy of a nucleoside polymerase and protease
inhibitor. The results were significant antiviral potency and sustained viral
reductions. In addition, the therapy appeared safe and well-tolerated. "The
expected better tolerability of these IFN-free combination DAA regimens may
make treatment easier for patients and also allow for patients to be treated
who are unable to take interferon based therapy," said Edward Gane, MD, lead
investigator on this study. "The greater numbers treated and better success
rates should eventually help reduce the future projected burden of end-stage
liver disease for chronic HCV."

The INFORM-1 trial is randomized, double-blind, and placebo controlled. The
oral therapy was administered over a 14-day period, and the antiviral
responses were impressive among all groups. It was reported that the
combination is undergoing further development for treatment of chronic
hepatitis C. "This is the first study to demonstrate that an IFN-free, twice
daily, combination DAA regimen produces similar antiviral activity compared to
triple therapy (SOC plus protease) over 2 weeks of treatment," said Dr. Gane.
"This combination may represent the first IFN-free treatment regimen for both
treatment-naive and previously treated patients with HCV Genotype 1
infection."

These results are very promising in regards of antiviral potency and lack of
resistance development. "From here we will need to explore in a stepwise
fashion if longer treatment will result in persistent viral suppression, clear
all HCV-infected hepatocytes and ultimately lead to a sustained virologic
response (SVR)," said Dr. Gane. He concluded by saying, "as we explore this
new treatment paradigm, we hope to gain a better understanding of the virus
host interaction in HCV, as DAA induced viral suppression in the absence of
extrinsic interferon allows us to study intrinsic interferon responses and
associated biomarkers."

Abstract title:
Combination therapy with a nucleoside polymerase (R7128) and protease
(R7227/ITMN-191) inhibitor in HCV: Safety, pharmacokinetics, and virologic
results from INFORM-1

[Rockerforlife]

R7128 is the one to keep your eyes on,boceprevir and teleprevir are also very powerful but this R7128 is amazing,i can see this drug getting tons of attention.

[epiphiny]

Ed Gane is/was my Doc when I was on the trial and when I was treating.  He was talking to me about this trial and it's result when I saw him on 22nd October.  He believes these non INF treatments are not as far away as people may imagine.  He's very excited about the results and believes this will be the way of the future for those people not succesful with SOC.

I am not sure why they are not getting as much press, perhaps because they were originally discovered by a little known pharmaceutical company which has since sold them to Roche which has the money to get more trials up and going.  I do know the FDA have fast tracked R7128 as it is clear it has the potential to cover a much needed gap in treatment options for the hard to treat HCV population.

As to targetting the trial at Geno 1 i believe it is simply that because there are more Geno 1 in the world, particularily in The States where other Genotypes only make up about 2% of the HCV population.  Therefore most of the resources are aimed there and will undoubtedly gain faster approval.  Ed seemed to think that non INF treatments for other Genos were about 10 years away, and about 5 years or less for Geno 1s.

The factor that R7128 has going for it above other PIs is that it works across ALL the geno's whereas Teleprevir and Boceprevir are working well for the 1's but not the 3's. I can't believe how fortunate I was to have Ed as my doctor, and how fortunate I was to get R7128 esp being a G3 relapser which muct be a pretty small percentage worldwide!

Big ups to Ed and his study team. They rock!

[mike716]

It may be a long time yet before such non-SOC Tx is approved. It looks like the polymerase inhibitors themselves, though, have been in trials for a while, maybe even for as long as the protease inhibitors. Is there a good reason why they (the polymerase inhibitors) are getting so much less press than the protease inhibitors?

Thanks.

Mike

[annieCinMD]

I'm way interested in watching this one. I had an awful time on interferon, and still having sides. Only will do ifn again if I have to!

[DragonSlayer45]

Thanks for that info. Yes Epi did treat and clear. She was the only other from the trials that I knew of that posts here regularly.

[Kristina538]

A G1 friend of mine had this tx mentioned to her.  I thought, that because we were in New Zealand, we would be later to receive it.  

Thanks DragonSlayer - I have sent her the link.   Dr Ed Gane is the top guy in New Zealand so, if he is in Boston discussing it, I would hope we'll be trialling it here.  She finished 48week SOC a few months back.    Excellent news - I was hoping to hear something about this 2 week non-SOC tx trials soon!!  

BelB64 - I believe Epiphany (G3) used the R7128 with SOC for her second tx and cleared.   I'm thinking that the G1's may have tabs on the first tx's, and look forward to hearing whether it may be of use to the other G types also.

[DragonSlayer45]

BelB64

Can't comment on it as I really know as much as you. Just thought it was interesting article. I would assume because it is so early that they tried this on geno 1 since it is the hardest to treat or the most prevalent. As with all these drugs they take baby steps first. As I mentioned it is way to early to get too excited but I thought it sounded interesting to say the say the least.

Robo,

yeah it would be great if they could lose the SOC portion of care. For now and the foreseeable future it is going to part of the mix.

[BelB64]

I'm surprised that since R7128 was SO successful with SOC in trials for genotypes 2 and 3 Dr Gane only mentions Genotype 1. Wouldn't you think this will be as effective against all genotypes as that is what Pharmassett has always said about R7128.

[robo229]

DS,

Great news!

This is exactly the news we need.  Treatment options without the "SOC" side effects.

As you know,  I contacted you some time ago about the INFORM trial.  I'm glad more positive news is out there.  

This cocktail treatment design is result of what was learned in designing HIV tx options and shows real forward thinking as it is applied to HCV.

Robo