R7128-Polymerase Inhibitor

These are results of the phase 1 trails,i am trying to get my brother into the phase 2 trials right now,this looke very exciting:

In a 4-week Phase I combination study conducted in 81 treatment-naive patients with chronic HCV, R7128 demonstrated significant short-term antiviral activity with safety and tolerability comparable to placebo with standard of care. Up to 88 percent of patients achieved undetectable levels of HCV (<15 IU/ml) after only 4 weeks of treatment with R7128 1000mg bid and the standard of care, compared to 18.75 percent treated with the standard of care alone.   -- In the harder to treat populations of genotype 2 or 3 patients who had not responded to previous therapy, results with R7127 1500mg twice-daily in combination with the standard of care showed that 90 percent of patients achieved undetectable levels of HCV(<15 IU/ml) after 4 weeks, compared to 60 percent in the standard of care arm.    



http://www.news-medical.net/news/2009/04/26/48859.aspx

[Isobella]

Thanks for the link.  My hepa thought this drug showed lots of promise.  

[Rockerforlife]

Yes,this drug works a bit different on the cells in the body from the PI drugs,im still reading up on it but i thing it works on the nucleus of the cell rather than the enzyme inside the cell,its very interesting.But look at the VL reductions by week 4,,almost 90% RVR`ed.

[Rockerforlife]

This is how the Polymerase Inhibitor(Nucleoside Analog) works on the virus:

Definition: An artificial copy of a nucleoside. When incorporated into a virus DNA or RNA during viral replication, the nucleoside analog acts to prevent production of new virus. Nucleoside analogs may take the place of natural nucleosides, blocking the completion of a viral DNA chain during infection of a new cell by HIV. The HIV enzyme reverse transcriptase is more likely to incorporate the nucleoside analogs into the DNA it is constructing than is the DNA polymerase normally used for DNA creation in cell nuclei. There are currently ten nucleoside analogs approved for marketing in the United States

http://findarticles.com/p/articles/mi_m0EIN/is_2007_Nov_19/ai_n27450686/

[Rockerforlife]

I know the above article is referring to the HIV virus but it also works the same with the HCV.

[Rockerforlife]

The licensed compounds include a series of nucleoside analogs that inhibit NS5b, an RNA-dependent RNA polymerase that is a critical enzyme in the lifecycle of HCV. In vitro studies using a HCV genotype 1b subgenomic replicon system demonstrate that these nucleoside analogues are among the most potent HCV polymerase inhibitors in development.

[Rockerforlife]

I find this interesting:

The present invention provides nucleic acid based polymerase inhibitors and methods for reducing non-specific polymerase extension and amplification in nucleic acid amplification reactions. The polymerase inhibitors provide a double stranded nucleic acid portion that is recognized by a polymerase enzyme as a template for extension but is incapable of being extended by the polymerase enzyme. The polymerase binds to the polymerase inhibitor which sequesters the enzyme until the temperature achieves a level that denatures the double stranded portion of the inhibitor after which the polymerase is released and can then catalyze nucleic acid extension.

[DragonSlayer45]

Rocker,

I wish your brother luck if he gets in the Phase II trial. This is a very promising drug. I participated in the Phase I as a geno 1 and cleared in 4 weeks. The phase II will  shorten the Peg and Riba part to 24 weeks. I felt all along this was the way it was going and that 24 weeks will be effective. 48 weeks with peg and riba was not a picnic. I am curious to see what comes out of this weekend AASLD about it.

I had my 6 month post tests and I am just awaiting the results. I am confident they are good. This is a great drug.  

[Rockerforlife]

Thanks Dragon:
This is good news,im grateful you told me this as this may get him to particpate,as i think hes scared.I gave him all the info and i even set him up.I called the main guys Roche and i ha a fine talk with them.Ill be praying for your SVR.Yes ,this POLY looks even better tan the Boceprevir.How were your sides,not bad i take it.?If you RVR`ed....ill bet you are done.

[DragonSlayer45]

Rock,

The R7128 in itself had no sides, it was the peg and riba that kicked my a$$ (mostly the interferon). Interferon in particular is nasty stuff. I had a lot of sides from that. This trial from what I see will give you R7128 (unless in placebo arm) for 12 weeks with Peg and Riba. That is followed by another 12 weeks of Peg and Riba alone. Each arm gets a different dosage of the drug and one arm gets a placebo. All arms get the Peg and Riba. Tell your brother if he decides that he is going to participate tell him to keep in mind that trials are just that "trials". While this is a promising drug there is no guarantees that he will clear. That is not the purpose of these trials per se. They are investigating dosages and the pharmacokinetics etc. The phase II also will incorporate a larger Number of patients (400). the Phase I was only 81 patients. So this is far from being an approved drug. There have been many drugs farther along than this that have been shelved before. Having said that I personally do not think that will be the case with this drug. While I am excited about the prospects of this drug I am just trying to keep it in perspective.

The Phase I trial we were given R7128 for 4 weeks with Peg and Riba. We then took Peg and Riba for an additional 4 weeks. At that time you were given the option of continuing with Peg and Riba for another 40 weeks (which I did). As I mentioned earlier I cleared in less than 4 weeks and stayed there. I felt all along that this treatment would be tried as a 24 week therapy and that is what this trial is. Now you get the R7128 for 12 weeks instead of 4.

Good luck to your brother in his decision. Don't push him let him though. This is a personal decision each and every one of us has to wrestle with. Only the person treating can make that decision.  All anyone can do is arm themselves with as much information as they can and then make an educated decision based on each one of our own circumstances and comfort levels. Participating in trials is not for everyone. We are the human guinea pigs, no one should ever lose site of that. Now is when they try and discover more about the drugs and how they interact with our bodies and other drugs. If all goes well they eventually become approved by the FDA. It is a long road to approval. Good luck!