2 log drop

[roscoe1]

hey, its roscoe. my friend just called, yall know her by diane04. she had a over 2 log drop in 1 day. went from over 11 mil to 46 thousand from first shot. she is hoping to be undetectable right now. any way she is currently indisposed but will be posting soon, wanted me to touch base. oh yea she is on the roche r7128 niave trial. whats her chances of svr? i am hoping to get on the next trial, she is a trooper. in good health roscoe

[epiphiny]

I was on the Phase 1 (Part 3) R7128 trial which started May 2008 and as far as I know was the first trial on humans.  It was reported that 95% of the patients achieved UND by week 4 but as to how many people have gone on to achieve to SVR is too early to tell.  

I was one of the first to to start the trial and my 6 month post PCR is not due until October 2009.  I am not sure about any of the 24 week arms (if there were any) as they would have just passed the 6 months post mark. I did 48 weeks as I was Gen 3 nonresponder.  As far as I know all Gen 3's on my arm went for 48 weeks.

I had a 6 log drop by week 4 which is considered Rapid Viral Response (RVR), I'm not sure what they call a Super RVR such as you describe Diane has had but I would call it fantastic!

I had my 3 month post PCR about 3 weeks ago and I still remain undetetctable.  If I am still undetectable in October they will consider me SVR.

Following is an excerpt from the reports from the studies so far:

Part 3 is a 4-week study of R7128 in combination with Pegasys (pegylated-interferon) plus Copegus (ribavirin) in up to 75 treatment-naïve patients chronically infected with HCV genotype 1, and additionally, in up to 25 prior treatment non-responders, or patients who did not achieve an SVR with previous interferon-based therapy, who are chronically infected with HCV genotypes 2 or 3. The primary objective of this study is to assess the safety, tolerability, and pharmacokinetics of R7128 in the clinically-relevant setting of combination therapy with the current standard of care for chronic HCV infection. The secondary objective is to evaluate the short-term change in HCV RNA. The study will include three oral dose regimens of R7128 (500 mg, 1000 mg and 1500 mg) in patients chronically infected with HCV genotype 1 and one oral dose regimen of R7128 (1500 mg) in patients chronically infected with HCV genotypes 2 or 3. All four dose regimens are being administered twice-daily with Pegasys plus Copegus for 4 weeks. There will be 25 patients in each dose cohort with 20 patients randomized to receive R7128 and five patients randomized to receive placebo, all administered in combination with the standard of care. After completing 4 weeks of the triple combination regimen and a follow-up period of four weeks of Pegasys plus Copegus, all patients will then receive 40 weeks of open-label standard of care dosing under a separate protocol. Results from the 500mg and 1500mg dose cohorts in 50 treatment-naïve patients chronically infected with HCV genotype 1 indicated:

    * Following 4 weeks of treatment with R7128 1500mg BID with Pegasys plus Copegus, patients achieved a mean 5.1 log10 IU/mL decrease in HCV RNA and 85% (17 of 20) achieved undetectable levels of HCV RNA (<15 IU/ml), or rapid virologic response (“RVR”).

    * Following 4 weeks of treatment with R7128 500mg BID with Pegasys plus Copegus, patients achieved a mean 3.8 log10 IU/mL decrease in HCV RNA and 30% (6 of 20) achieved RVR.

    * Following 4 weeks of treatment with placebo with Pegasys plus Copegus, patients achieved a mean 2.9 log10 IU/mL decrease in HCV RNA and 10% (1 of 10) achieved RVR.

    * Safety and tolerability for the 4-week treatment period were similar for R7128 with Pegasys plus Copegus compared to placebo with Pegasys plus Copegus. There were no serious adverse events reported during the 4-week treatment period, and most of the adverse events reported were of mild to moderate intensity. The most common adverse events, reported in 15% or greater of patients in any treatment group during the 4-week treatment period, were headache, injection site reaction, myalgia, fatigue, chills, rash, nausea, diarrhea, arthralgia, pyrexia, dizziness, dyspepsia and pruritis. The frequency and severity of these adverse events, as well as any general body system observations, were generally similar to clinical experience with the standard of care for HCV, pegylated interferon plus ribavarin. Grade 3/4 neutropenia was observed in 30% of the placebo patients and in 10% to 15% of the R7128 patients in each active dosing cohort. Grade 3 changes in hemoglobin were observed in 10% of the placebo patients and in 15% of the R7128 patients. There were no clinically significant changes in other hepatic, renal, or other safety laboratory parameters, vital signs, or electrocardiograms. Overall, there was no clinical evidence of any major organ toxicities related to R7128. One patient in the active treatment group discontinued the study during the 4 week treatment period due to lower-gastrointestinal adverse events. At the time of study discontinuation, this patient had undetectable HCV RNA. R7128 was generally safe and well-tolerated when administered for 4 weeks in combinations with Pegasus plus Copegus in patients with HCV genotype 1.

Here's the web link for further info:

http://www.pharmasset.com/pipeline/R7128.asp

And this is all the publications and presentations that have been presented to medical community at conferences etc.

http://www.pharmasset.com/pipeline/R7128-publications.asp

Tell Diane she is doing great and she has a high chance of success.  Important to follow all protocols and make sure she takes all the drugs, every day, twice a day, approximately 12 hours apart WITH FOOD, esp some fatty food to help the riba stay in her system as long as poss and increase absorption...

Annie:  I have heard most of the virus slaughter takes place in the first few days, the added SOC and extra time after that is to make sure any mutations that are hiding at a cellular level are also destroyed...

All the best
Epi :)

[banarep]

which protease inhibitor were you on?

[annieCinMD]

I've never heard of getting tested after one day, but it sounds like one heck of a way to start! If r7128 is a protease inhibitor, and she's on that as well as SOC, then I'm not overly surprised. I cleared within 2 weeks of adding a protease inhibitor to my treatment. Now, I don't know exactly WHEN in that 2 week period it happened, but those protease inhibitors can plant a foot firmly in the backside of the virus. Lot's of posts on here to back that up. The virus needs protease to make copies of itself. If you take protease out of the picture, it can't replicate, plain and simple.