R7128 new trial

[dointime]

http://www.hcvadvocate.org/news/newsRev/2009/NewsRev-292.html#_Pharmasset_and_Roche

Pharmasset and Roche Obtain FDA Consent to Start a Phase 2b Study With R7128 in Treatment Naive HCV Patients
http://www.pharmalive.com

PRINCETON, N.J., Jan. 12 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (NASDAQ:VRUS) announced today that they and their development partner, Roche, have agreed with the FDA on the final design for a phase 2b trial with R7128, a nucleoside inhibitor of hepatitis C (HCV), slated to initiate in the first quarter of this year.

"We are pleased that R7128 is advancing into a large phase 2b trial," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "R7128 is the most advanced nucleoside polymerase inhibitor in development and we believe this class of drug brings a number of advantages to HCV-infected patients. R7128's higher barrier to resistance and activity across multiple viral genotypes, as well as the promising short-term safety and tolerability, may bring patients a new option for therapy. We look for this trial to better define the optimal treatment duration with R7128 in combination with the standard of care."

The phase 2b trial is anticipated to enroll about 400 treatment naive, genotype-1 or genotype 4 HCV-infected patients. The trial will evaluate the dose and duration of treatment of R7128 in combination with Pegasys(R) plus Copegus(R). The primary efficacy endpoint of the trial will be the proportion of patients that achieve a sustained virologic response (SVR), defined as undetectable (measured by Roche TaqMan assay) HCV RNA 24 weeks after completion of treatment. Patients will be enrolled into one of 5 arms:

    * 24 weeks of total treatment, with R7128 500mg bid in combination with pegylated interferon and ribavirin for 12 weeks, followed by 12 weeks of pegylated interferon and ribavirin
    * 24 weeks of total treatment, with R7128 1000mg bid in combination with pegylated interferon and ribavirin for 12 weeks, followed by 12 weeks of pegylated interferon and ribavirin
    * 24 weeks of total treatment, with R7128 1000mg bid in combination with pegylated interferon and ribavirin for 8 weeks, followed by a further 16 weeks of pegylated interferon and ribavirin
    * 48 weeks of total treatment, with R7128 1000mg bid in combination with pegylated interferon and ribavirin for 12 weeks, followed by a further 36 weeks of pegylated interferon and ribavirin.
    * A control arm with pegylated interferon and ribavirin for 48 weeks.

Patients in the 24 week arms will discontinue treatment at week 24 if they achieved a rapid virological response (RVR), defined as undetectable level of HCV RNA at week 4 ("RVR-guided"). Patients that do not achieve an RVR will continue on the standard of care until week 48.

According to the current study design, patients will be enrolled as two cohorts, with randomization of the second larger cohort being initiated based on 12 week safety data of the first cohort.

During 2009, we expect to provide updates on the progress of the trial.

[epiphiny]

Hey, thank you so much for posting this info.  It's really great and encouraging news as I am in the SOC stage of the Phase 1 trials that started in May 2008.  

I was a previous non-responder to SOC treatment and was on R7128 for 28 days plus SOC and I was UND at week 4.  I have 11 weeks of my 48 weeks to go, still UND and feel a great deal of hope for achieving SVR.  

Because this is such a new drug and there's only been a few small trials so far there is not much info out there and not many people have been enrolled on the trials.  I have only met one other person on MedHelp.

I know feelings have no place in science BUT I feel this drug could be a winner, based on my experience with it.  Fingers crossed.

If anyone gets the opportunity to get on this trial I would highly recommend it.

Epi.

[dointime]

This is wonderful news and very important for us to know that you were a previous non-responder.  There's a big question mark hanging over SOC non-responders concerning whether the new drugs will be able to get them to SVR.  I personally did get to UND on my previous attempts but then got viral breakthrough.

So please keep us posted on how it works out for you.  As you say, there are not many people out there with experience of R7128.  I have hopes for it to be my first choice for my next tx.

Fingers crossed for you.  
Best of luck

dointime    

[DragonSlayer45]

This is going to be another great trial. I am the other person Epiphany is referring too. I am also still currently enrolled in the phase 1 trail. I am in week 33 of 48. I am a geno 1a and had a beginning VL of 8 million and it dropped to UND by week 4 and has stayed there since.

The phase 1 trial gave me 1000mg./day R7128 for 4 weeks along with Peg and Riba (triple therapy). Then just peg and riba only for 4 weeks bringing the total to 8 weeks. You then had the option of rolling over into an omnibus study and continue the peg and riba for another 40 weeks (free from Roche) to make it a 48 week treatment. You could also have just stopped, or gone to your insurance to pay for it (why anyone would do either of the last 2 I do not know).

The success rate was over 85% clearance rates for genotype 1 non-responders and  90% for geno 2 and 3 non-responders. Very impressive results. Keep in mind that it is still too early for any SVR data, but I am willinng to bet that if you clear at week 4 and stay clear all the way through your chances of SVR are excellent.

The only side effects from this treatment are from the peg and riba. There have been no adverse effects found the R7128. This is one of the better drugs to come down the drug pipeline in a while.

I know there have been a lot of people who love the telaprevir trials, and they are also having tremendous success. I almost enrolled myself in that one but frankly it has some adverse sides and showed some early viral mutations that kept me away. None of that has been found with the R7128 trials. If anyone is looking for a trial to go into this is worth looking at closely. I truly believe it is going to surpass the others.

I am curious to see how this trail does with the 24 week regimen. If I was to have any knock on these trials is the fact that they all still have to be used with peg and riba. As many of us have treatted before or are treating now know. That treatment is not an easy one.

I would also recommend that anyone who is thinking about trials DO YOUR HOMEWORK and educate completely about what they entail and know ahead of time what all the possible sides from the new drugs and old grugs are going in. Enter anny treatment with your "eyes wide open" Do nnot blindly follow someones advice whether it be someone here onthe forum or even your doctor. Educate yourself.

Also as a side note I read a report that pharmasett, Roche, and Intermune are conducting a study in Australia and New Zealand that will for the first time combine a these newer drugs polymerase and protease inhibitors in a treatment with NO interferon. THAT is going to be exciting to watch.

If they can develop treatment without the use of peg and riba it is major victory for all hep C suffers.

[dointime]

Hey dragon, good to hear from you!

I take it you tx'd previously and were a non-responder?  

The more I hear about R7128 the more I like it.  Very effective, no sides, no resistant mutations.  Sounds too good to be true, but I'll take it!  

What is really surprising me is that both you and epiphany are remaining UND on SOC alone even although you are SOC non-responders.  That must mean either -

1.  The R7128 finished the virus off totally in 4 weeks, job done.
or
2.  Non-responders start to respond when viral load goes below the level of    detection.  Because if there are any survivors after the R7128 then it is the SOC that is keeping them in check and hopefully finishing them off.  

This is an entirely new idea for me.  I've never heard of it anywhere before.

dointime          

[DragonSlayer45]

Actually after just rereading my original post that was a typo. I was  Genotype 1 treatment Naive. The other leg was for non-responders geno 2 and 3. Sorry for the mis-communication. but yes UND since week 4. Just remember the SOC totally is no picnic.

[DragonSlayer45]

Also, I thought I just might add that the R7128 is not effective as a monotherapy. When combined with SOC it raised 42% to 85 % (for type 1's). I also find that a 6 log drop (for me) in 4 weeks as impressive. I definitely would consider trying it. Hopefully you don't get on the placebo arm. I have no stake in Pharmasett, I just think this is another potent future weapon against this disease. So far it looks very promising.

[Mary4now]

Thank you for the information, it is very hopeful for me.  I am treatment naive genotype 1, but i'm 59 yrs. old and have probably had it for over 30 yrs. But who knows for sure?  My at risk behavior stopped about 25 yrs. ago.  
The new drug sounds good.  good news.  

[zazza]

Do you have any PCR readings from your first tx? Would be interesting to know more about your response/non-response that tx.

[epiphiny]

The first time I treated it was still in the dark ages here in NZ and they only did qualitative testing not quantitative (due to costs and public health protocols).  It was only 2003/2004.  They may not seem like the dark ages but when it comes to treating Hep C the NZ health system is definitely behind the times.

I think my Riba was under dosed as against being a non-responder but we will never know....