Monotherapy in Phase 2

Question

Does anyone know of a new Hep C drug that is in Phase 2?  Supposedly this drug is highly effective (100%) and is a monotherapy drug.

My case manager was talking with me today and she said a GI doctor from Texas said that there is currently a monotherapy drug at Phase 2 and supposedly the drug is 100% effective at attaining SVR.

gonnabhepcfree · Answer

3 is my genotype..

curiouslady1 · Answer

Sorry, it doesn't come up from that link.

Hepatitis C PSI-7977 -Pharmasset Announces 91% SVR12 From the PROTON Trial -Naive Genotype 1 
0
Tuesday, September 6, 2011
Posted by New HCV Drugs
File Under geno1, PSI-7977 
Pharmasset Announces 91% SVR12 From the PROTON Trial in Subjects With Hepatitis C Genotype 1
Tue September 6, 2011 6:45 AM

PRINCETON, N.J., Sept. 6, 2011 /PRNewswire/ -- Pharmasset, Inc. (VRUS), announced today sustained virologic response (SVR) results from its phase 2b PROTON study with PSI-7977 400 mg dosed once daily in combination with peginterferon alfa 2a and ribavirin (Peg-IFN/RBV) in subjects with hepatitis C virus (HCV) genotype 1 who have not been treated previously. 43 out of 44 (98%) evaluable subjects achieved an SVR12, defined as HCV RNA below the limit of detection (<15 IU/mL) 12 weeks after the completion of treatment. All enrolled subjects will be followed to determine SVR24, the primary efficacy endpoint of the study.

Ninety five treatment-naive patients with HCV genotype 1 were enrolled into two open-label arms of the PROTON trial, receiving either PSI-7977 200 mg QD (N=48) or 400 mg QD (N=47) for 12 weeks. Individuals in both arms received Peg-IFN/RBV for 24 weeks and were followed post-treatment to assess SVR12. Twenty-six subjects were enrolled in a placebo control arm and are receiving 48 weeks of Peg-IFN/RBV. Results from this study through the SVR12 endpoint are scheduled to be presented as part of a Presidential Plenary Session at the American Association for the Study of Liver Diseases (AASLD) meeting on Tuesday, November 8, 2011.
"I am very pleased with the results of this study which clearly demonstrate the benefit of the 400 mg dose of PSI-7977 with only 24 weeks of interferon for all subjects," stated Dr. Eric Lawitz, the study's principal investigator. "HCV therapy is becoming overly complex, and the elimination of 24 weeks of interferon and ribavirin as well as all response guided criteria for patients with HCV genotype 1 would be a welcomed simplification."

At the European Association for the Study of the Liver (EASL) in April 2011, Dr. David Nelson presented interim results from the PROTON trial showing that 43 out of 47 subjects receiving the 400 mg dose of PSI-7977 achieved an eRVR, defined as HCV RNA below the limit of detection (<15 IU/ml) at week 4 through week 12. Of those not achieving eRVR, 3 discontinued therapy early due to unrelated adverse events and 1 was lost to follow-up, as previously reported. Notably, one of these individuals went on to achieve an SVR12 in spite of the shortened course of therapy. The combination of PSI-7977, pegylated interferon and ribavirin was generally safe and well tolerated.

About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Our research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates advancing in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered uracil nucleotide analog, is currently under study in four Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the Pharmasset purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in three Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.

Contact Richard E. T. Smith, Ph.D. VP, Investor Relations and Corporate Communications Office +1 (609) 865-0693

curiouslady1 · Answer

Bill,  don't know too much yet.  But here is something interesting.  Note that if they didn't have the drop outs due to unrelated events, it would have been closer to 100%

http://hepatitiscnewdrugs.blogspot.com/2011/09/hepatitis-c-psi-7977-pharmasset.html

Bill200 · Answer

Gonnabfree, what is your genotype?

Curiouslady, is there any data out on PSI for GT 1?

curiouslady1 · Answer

You really need to change your name gonnab; maybe to "been there, done that":) The study coordinator at my site said basically the same thing.  They are advising more people to wait.   She actually came out and said that they thought the triple was worse than the SOC.  I am not keen on the Gilead drugs as all orals as there have been a number of failures on this forum alone.  However, with SOC I suppose they are doing ok.  

I am done dosing with BMS/PSI on February 7 with two other study mates but I think attagrl and her mom are finishing at the same time you are.  Somebody back channeled me that a group is ending within the next week or two though I hadn't heard that anyone was that far ahead of us.  

I am fatigued a lot due to poor diabetic diet control and failure to wear my CPAP which has nothing to do with the trial.    However, I did have to give up my proton inhibitor for the duration of the trial because it could interfere with absorption of the BMS drug and so my heartburn is bad.  But there hasn't really been anything related the the trial medication.

PS I haven't heard from attagrl since she ran the half marathon about a month after we started the dosing.  She was never a big one on keeping up with this forum though.

christinaf28 · Answer

It's brilliant news !! They seem to be very effective .. It gives us hope

gonnabhepcfree · Answer

I am not really sure how many in my study location. I know that my usually reserved Dr is visisble excited about the all oral regimes((he has several Gilead etc all orals) and said that he's sees in the not so distant future (don't know how far out that is) people not even needing specialist but just going to there Primary for treatment of Hep C. He also said that it's just finiding the best combo with the least side effects.. My study coordinator said that he is not starting anyone that can wait for treatment on interferon.. I am going to confirm that with him next time I see him. I will be done on Feb 1 with medication and then once a month labs for 48 weeks. I thought it was only for 24 but she told me on my last visit it's 48. How have you been feeling? Anymore fatique?

sejmiig · Answer

I just recently learned the same thing, AND it does not have all the horrible side effects that incivek and all the other crap has.  while I'm glad I did all this and it appears to have worked, having had it for probably 15 years (they just figured it out last year) I think I could've waited....

curiouslady1 · Answer

Hey gonnab, how many people at your study location?  I know of 9 people including you and me that are still UND since the early weeks of the BMS/PSI study.

pooh55811 · Answer

Thanks for all of the responses and links.

gonnabhepcfree · Answer

I am in the PSI 7977 and BMS 790052 so I started in July and was und in seven days and that hasn't changed for myself of ANYONE else at my study location.  No side effects except mild fatigue in the beginning.  (mild meaning instead of walking four miles a day I walked two.  Google search Hep C new driugs there are some great information about all the trials that are easier to read than the Gov site and then go there for locations.  Good luck..

curiouslady1 · Answer

These are the ways that people use to find out about these trials.  They go to clinicaltrials.gov and type in the search box PSI 7977 AND (name of state).  When you find a likely trial, you go down the page and you will see locations with contact numbers.  Sometimes there is a drop down box that you will need to click on.  You can also go to pharmasset.com and look around the site for more information particularly about trials coming up which may not be listed at the government web site yet.  If you cannot find a contact number for your own state, you try a nearby state.  Some people travel hours to get into the right trial.   Some research sites will give a stipend that enables study subjects to travel.  You also check anything that may have news of a trial. I have even gone into their stock market page and there are sometimes brief articles that have info of a new trial coming up.  Then you check any research center that might have information that you want.  I have posted a number of these resources on my journal page for this particular group of drugs because I feel they are better than the average under study.

jerialice · Answer

any info on WHO to talk to about getting on a trial of the
PSI 7977????
thx!

pooh55811 · Answer

It would be interesting to know. Too bad my case manager did not ask that doctor what the name of the drug is (or maybe it cannot be disclosed).

curiouslady1 · Answer

Yes both PSI 7977 and PSI 938 are both being tried as monotherapies.  But it will be a long time before our trials are done dosing and have achieved SVR (6 months later).  How are you doing Susie?  Are you in Quantum?

SusieS2010 · Answer

One of the arms of the pharmasset trial I am in is with 7977 and ribavirin or placebo for ribavirin. That may be what you ar talking about.

pooh55811 · Answer

Thanks, it is all very interesting. It would su8re be great if they can develop some drugs that have a lot fewer side effects.

curiouslady1 · Answer

PSI 7977 was effective 100% with a small group of  GT2 and 3 and the study was presented at the AASLD.  I am not sure if it was alone or with Ribaviron. But one must be cautious in how to interpret these findings.  GT 2 and 3 are usually easier to treat and the group was small.  The trials on GT 1a and 1b and others are being done now but with two oral drugs 7977 and others in combination.  Many people are getting rapid responses with a minimum of side effects.  However, I spoke with my PI re this issue as we are about 3 to 5 months in on these trials.  She indicated that it is not expected that there will be 100% SVR when all is said and done.  When you think of having a large number of people involved and their own idiosyncratic pill taking behavior and other vicissitudes of physical condition and genetics you might imagine that such a result is unlikely.