AASLD 09...let's talk results, lead ins, inovio, etc

ASSLD in boston coming up...I don't know about anyone else but I've got a wish list for things I'd prefer my clinic's team to focus on,

add your wish list to mine.

mine includes

A, the Inovio vaccine that wipes out 99% of the virus of those infected (would make chemo a mop up by comparison, and lessen tx times.

B. a comprehensive redress on tylenol toxicity...too many docs had it drummed into them to be thinking this drug safe, which for liver patients it is not.

C.Why is no one getting excited about the boceprevir trial results. They are the only ones who tried the "LEAD IN" approach which improved SVR to 93% in EVR which is huge. I hope some docs pick up on this.

D. Comprehensive stategies to allow stage 1 and 2 people to treat. Currently many insurances are refusing to treat early stage patients. The chances of SVR go down significantly with each stage progression, plus as the endocrine system is affected other diseases emerge. The effect of refusal to treat early means many are being condemned to far less chance of SVR, not to mention other serious health issues. Here an ounce of cure could become pounds of productive years and better health.

add your wish list to mine



merrybe

[merryBe]

Adding Boceprevir to PegIntron/Ribavirin Significantly Improves Sustained Virological Response in Chronic Hepatitis C Patients

By Liz Highleyman

Combination therapy using pegylated interferon (Pegasys or PegIntron) plus ribavirin -- the current standard of care for chronic hepatitis C virus (HCV) infection -- is associated with numerous side effects and about half the time does not produce a sustained response. In an attempt to improve outcomes, researchers are studying several oral agents that directly target various steps of the HCV lifecycle, an approach known as "STAT-C."

At the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last week in Copenhagen, investigators reported final results from the Phase 2 HCV SPRINT-1 study, which evaluated the safety and efficacy of Schering-Plough's investigational HCV protease inhibitor boceprevir in various combinations with pegylated interferon alfa-2b (PegIntron) plus ribavirin.
A three-dimensional modelof boceprevir, a potential next generation Hep C drug candidate.

SPRINT-1 included 595 treatment-naive patients with genotype 1 chronic hepatitis C in the U.S., Canada and Europe. Overall, 16% of participants were African-American, 7% had pre-existing liver cirrhosis, 56% had HCV genotype 1a, and 89% had high HCV viral load (> 600,000 IU/mL), all factors associated with poor response to interferon-based therapy.

Boceprevir (800 mg 3 times daily) was evaluated as part of 3 treatment regimens:

    Lead-in therapy with 1.5 mcg/kg once-weekly pegylated interferon plus 800-1400 mg daily weight-adjusted ribavirin for 4 weeks, followed by the addition of boceprevir for 24 or 44 more weeks (for a total of 28 or 48 weeks of treatment);

    Boceprevir in combination with the same doses of pegylated interferon plus ribavirin, with all 3 drugs taken together for 28 or 48 weeks.

    Boceprevir plus pegylated interferon plus low-dose 400-1000 mg daily weight-adjusted ribavirin for 48 weeks (Part II).

In Part I of the study, the boceprevir regimens were compared against the approved standard of care control regimen of 1.5 mcg/kg once-weekly pegylated interferon plus 800-1400 mg daily weight-adjusted ribavirin, without boceprevir, for 48 weeks.

In Part II, boceprevir plus pegylated interferon plus low-dose ribavirin for 48 weeks was compared against boceprevir plus pegylated interferon plus full-dose ribavirin for 48 weeks.

The rationale for the lead-in period was based on the fact that both pegylated interferon alfa-2b and ribavirin reach steady-state concentrations by week 4, therefore patients had boceprevir added after levels of the other drugs were optimized and HCV viral load was reduced, according to a Schering-Plough press release describing the study findings. This approach may minimize the duration of "functional monotherapy" with the direct antiviral agent, thereby potentially reducing the likelihood of developing resistance.

The primary endpoint of the study was sustained virological response (SVR), or continued undetectable HCV RNA after 24 weeks of post-treatment follow-up.

Use of erythropoietin (EPO) to manage anemia (defined as hemoglobin < 10 g/dL) during treatment was allowed at the discretion of study investigators.

[merryBe]

Results

    In the 28-week and 48-week boceprevir/pegylated interferon/ribavirin triple-therapy arms with no lead-in period, SVR rates were 54% (58 of 107 patients) and 67% (69 of 103 patients), respectively.

    In Part I of the study, response rates were improved in the arms with a 4-week pegylated interferon/ribavirin lead-in period before starting boceprevir.

    The 4-week pegylated interferon/ribavirin lead-in followed by 44 weeks of triple combination therapy produced an SVR rate of 75% (77 of 103 patients), compared with 38% in the standard of care control arm (39 of 104 patients) (P < 0.0001).

    The SVR rate was 56% (58 of 103 patients) using the 4-week pegylated interferon/ribavirin lead-in period followed by 24 weeks of triple combination therapy (P = 0.005 vs standard of care).

    In the lead-in arms, 64% of all patients achieved rapid virologic response (RVR), defined as undetectable HCV RNA 4 weeks after adding boceprevir.

    Among patients in the lead-in arms who achieved RVR, SVR rates were 94% using the 48-week regimen and 82% using the 28-week regimen.

    In Part II of the study, the SVR rate for the triple-combination regimen with low-dose ribavirin was 36% (21 of 59 patients).

    The low-dose ribavirin regimen was associated with an increased risk of viral breakthrough during treatment and a higher relapse rate after the end of treatment, resulting in a lower SVR rate.

    Overall, triple-combination therapy was well tolerated.

    In Part I of the study, 9%-19% of participants in the boceprevir arms discontinued therapy due to adverse events, compared with 8% in the standard of care control arm.

    Fewer patients in the 28-week and 48-week lead-in arms discontinued treatment due to viral breakthrough (4% and 5%, respectively, vs 7% and 12% with no lead-in).

    The most common adverse events reported in the boceprevir arms were fatigue, anemia, nausea, and headache.

    The incidence of skin adverse events (rash or pruritus [itching]) was similar in the boceprevir and standard of care arms.

    About one-half of patients in the boceprevir arms and about one-third in the standard therapy arm developed anemia during treatment.

    39%-51% of patients in the boceprevir combination arms and 26% in the standard of care control arm used EPO.

    Participants who developed anemia had a greater likelihood of achieving SVR than those without anemia.

"Both 28 and 48 week boceprevir regimens significantly increased SVR with very low relapse rates in 48 week regimens," the investigators concluded. "However, low dose ribavirin with PegIntron and boceprevir was associated with increased viral breakthrough, relapse and lower efficacy. In contrast, pegylated interferon/ribavirin lead-in prior to boceprevir substantially increased SVR and reduced viral breakthrough."

"These results are very exciting and provide important insights to help further define response guided therapy using a pegylated interferon/ribavirin lead-in boceprevir regimen with peginterferon and ribavirin backbone treatment," stated lead investigator Paul Kwo, MD, in the Schering-Plough press release. "Building on these results, the boceprevir Phase III clinical program individualizes treatment based on response, utilizing RVR criteria at week 4 of boceprevir treatment to determine overall duration of therapy. Based on the RVR rate seen in this Phase II study, we are hopeful that the majority of patients can be treated with 28 weeks of therapy."

Patient enrollment has been completed in 2 ongoing randomized, double-blind, placebo-controlled registration studies evaluating boceprevir in combination with PegIntron and ribavirin: HCV SPRINT-2 in treatment-naive patients and HCV RESPOND-2 in treatment-experienced relapsers and non-responders.

Indiana University School of Medicine, Indianapolis, IN; Alamo Medical Research, San Antonio, TX; Mount Vernon Endoscopy Center, Alexandria, VA; Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL; Baylor College of Medicine, Houston, TX; Indianapolis Gastroenterology Research Foundation, Indianapolis, IN; Digestive Care/South Florida Center of Gastroenterology, Wellington, FL; Liver Specialists of Texas, Houston, TX; Henry Ford Health Systems, Detroit, MI; Digestive Disease Associates, Baltimore, MD; University of California-Davis Medical Center, Sacramento, CA; Liver & Intestinal Research Center, Vancouver, BC, Canada; Weill Cornell Medical College, New York, NY; Digestive Healthcare of Georgia, Atlanta, GA; Schering-Plough Research Institute, Kenilworth, NJ.

4/28/09

Reference
P Kwo, E Lawitz, J McCone, and others. HCV SPRINT-1 Final Results: SVR 24 from a Phase 2 Study of Boceprevir Plus PegIntron (Peginterferon Alfa-2b)/Ribavirin in Treatment-Naive Subjects with Genotype-1 Chronic Hepatitis C. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009. Abstract 4.

Other Source
Schering-Plough. Final Results of Boceprevir Phase II HCV Sprint-1 Study Showed Significantly Higher SVR Rates Compared to Standard of Care in Treatment-Naive Genotype 1 Hepatitis C Patients. Press release. April 23, 2009.

[can-do-man]

merry wrote,

C.Why is no one getting excited about the boceprevir trial results. They are the only ones who tried the "LEAD IN" approach which improved SVR to 93% in EVR which is huge. I hope some docs pick up on this.
-------------------------------------------------------------------------------

Merry i just had my eot visit with Paul kwo who wrote the above article you posted, believe me there are alot of top doctors now paying close attention to boceprevir. They are very interested in this latest trial for relapsers that i was in. I was und within 2 weeks of starting boceprevir. BUT being a relapser and cirrhotic for some time only time will tell. As for the tx navie trials the results are very good.

Hope all is well

cando

[merryBe]

Boy, I'm really glad to hear you say that Can do.

Everybody seems to be on the Vertex bandwagon, and my clinic didn't know about the research, which is months old now...I had to tell THEM.

Well, at least I know they'll go to the conference knowing what patients have found out...

I've also made a big deal about the Insulin resistance issue...which increases SVR 10% when addressed.

As to how YOU do on the trial, wells here's hoping you make it.
getting UND that quick is really a good sign.
Did you see the genetic predictors stuff...(in Newleaf's journal)...maybe you are in that lucky group!!  I sure hope so. How long have you been in the trial??

mb

[can-do-man]

First i was in the 48 week arm.

I was lucky to have a consult by e-mail from Doctor Douglas T Dieterich, he is also one that is following this phase three trial and is excited by the prior results.

Also a post from magnum titled...........Boceprevir - doctors choice

http://www.medhelp.org/posts/Hepatitis-C/Boceprevir---doctors-choice/show/1078488

Cando

[susan400]

I just want them to come out of there with some way to help those of us who are considered "Telaprevir failures"...., I am tired of hitting a roadblock.  All they want to do is kick us to the curb, let us get worse....       I, fortunately, have been fighting back with doing everything in my power to stay healthy since, the doctors quite frankly aren't helping me right now.  I've been exercising like crazy, even when I really don't want to.  It's paid off for me, too.  I've lost weight and my blood sugar is in the normal range and my A1C has remained perfect for the past year..., not that I was ever termed a diabetic anyway, because I wasn't.  My blood pressure is perfect.  The ONLY thing that is wrong with my body is Hepatitis C and the fact that all the treatments have left me with a chronic, no-treatment for, skin condition..., where I cannot get in direct sunlight without being totally covered up i.e. long sleeves and long pants.   I just really want to be done with Hep C.  I want to kick it to the curb..., I want to post, I am SVR!!    Susan400

[newleaf09]

I suspect that Teleprevir and Boceprevir are giving very similar results.  I think the reason that Teleprevir gets so much attention is because they do a LOT of press releases.  They are a smallish biotech company that needs investors.  Schering Plough is a huge international pharma which is about to be bought by an even bigger one, Merck.  SP does not put out press releases, their info mostly just comes out as conference presentations and papers.  Buzz does not indicate anything, but it does cause people to favor one over the other just because they read more about one.  I think patients would be well served by either PI added to SOC.  Anxious to read the info coming from the AASLD meeting next week.

[merryBe]

Yes, I remember when Magnum finally got some relief...wonder how he's doing.

Well I'm glad to see some docs looking at the stats...the other issue of course is that Vertex skewed the numbers on their first study and never tried lead-ins, so theres no real way to be even comparing apples to apples, as the  techniques study don't match up nor can we know that this years Vertex numbers are accurate this time
. Somehow I find it incredulous that microbiologists wouldn't know how to do the mat
h in a double blind, since it's drummed into them add nausem.... and that calls all their trials into question in my mind.

Susan,

you break my heart, so much effort for so little reward....but you are a real trooper...hang in there, some real hope is on the horizon.
Yes, that's that same kick to curb that stage 1 and 2er's are getting.

I'm also trying the natural approach now, the long chemo pushed me into  type 1 as well as type 2 IR, diebetic (diabetic) territory so I'm really having to regroup on all of this.
I'm still waiting to hear if Inovio will be offering their vaccines soon...hopefully the Boston retrovirus conference will get news.
It would be so good to get the virus 99% ddead and then treat wih the 3 drugs for only 6 months

[Willy50]

(you wrote) "..the other issue of course is that Vertex skewed the numbers on their first study and never tried lead-ins, so theres no real way to be even comparing apples to apples, as the  techniques study don't match up nor can we know that this years Vertex numbers are accurate this time."
____________________________________________

The numbers that Vertex "skewed" was merely waiting to present the data (as required by the FDA) at a large liver conference. (the AASLD)  Investors claimed that Vertex "withheld" the data to inflate the stock value.  In actuality, if Vertex had prematurely released data such as in an investment stock presentation, that might have been considered "unblinding" of the study.  That's my understanding of the so called skewed numbers.

Vertex has indeed tried lead ins (predosing with SOC).  They have not released the data yet, although I believe that about 18 months has gone by and we may soon see that.

I don't always think that the companies want people to easily compare their drugs.  It seems like it took years to get a clear handle on comparisons to Peg-intron and Pegasys.  Since there was not clear proof each was entitled to claim the title of "best".  ; )
I think you can count on their data being solid, however.  The data is gathered by a 3rd party during the trials.  The data is presented to Vertex by that 3rd party (part of theFDA  blinding process) and so they don't even know everything at all times.  That at least, is my understanding.  

I believe that Boceprevir is a good compound and *could* even bet better than Telaprevir in some areas but I don't think we'll see that until they are compared on a level playing field with lead ins and use of rescue drugs.

best,
Willy

[merryBe]

thanks, that helps allieviate some fears for sure...of course if I had good numbers and a trial a year and a half old, AND a competitor with lead-in numbers, I'd be rushing to get mine out there...if they were better that is.

I agree, and that was one of my points, that we aren't able to compare apples yet.

That they didn't get the math wrong is not entirely comforting,
I mean, well,
why would anybody in their right mind unblind their own study....
especially when the drug that gets the final NOD will undoubtedly make an extra billion or two worldwide, assuming the drugs work as advertised.

mb

[copyman]

Who knows if Shering's data is accurate. After all with the amount of money at stake I wouldn't put anything past these companies. I feel both PI's are good and very similar in acheiving SVR.

[Rockerforlife]

Boceprevir Rocks....no rash either....i cleared after 2 weeks taking it....still clear 12 weeks post TX....my 6 month PCR  in first week in Jan 10.

[Willy50]

Here is a brief description of the difference in TX naives between Boceprevir and Telaprevir, although perhaps over the weekend Shering may have released new and better data.

The quote if from Adam Feurenstein in the article I posted in the recent Telaprevir thread in BID versus TID dosing which attained over 80% SVR rate;

--------------------------------------------------------
"Schering-Plough's boceprevir, which is the closest competitor to telaprevir, has demonstrated a maximum cure rate of 75%, although that required 48 weeks of total treatment.

Most of the patients in the study were treated for a total of 24 weeks, including 12 weeks of telaprevir. But 18% of the patients had their treatment extended to 48 weeks (still only 12 weeks of telaprevir) as part of the response-guided therapy. These patients didn't exhibit strong anti-viral response to telaprevir and standard of care early in the treatment cycle.

Serious adverse events forcing patients to drop out of the study occurred in 5% of patients, and were mainly related to rash (3%) and anemia (2%)."
-----------------------------------

Keep in mind.... this is still discussing 2 compounds in phase 2 trials.  The percentages could change.

best,
Willy

[Rockerforlife]

Schering-Plough's boceprevir, which is the closest competitor to telaprevir, has demonstrated a maximum cure rate of 75%, although that required 48 weeks of total treatment.

Not really true...the ones who cleared by week 4 after taking the Boceprevir,up to 95% got SVR

[Rockerforlife]

The ones who cleared between week 4 and 12 after taking the Boceprevir got 75% SVR

[Rockerforlife]

Importantly, for patients who received the boceprevir P/R lead-in regimen and had rapid virologic response (RVR), defined as undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment, SVR was 94 percent


http://www.medicalnewstoday.com/articles/130622.php

[newleaf09]

That's what drives me nuts about reading (and quoting) results.  The percentages jump around according to what you are looking at.  It's good to read the actual data so you can get a hopeful look at the group you yourself fall into.  The popular press stories are nice but the real picture is in the data.

[Rockerforlife]

If im still clear in  Jan....losing my job will mean nothing to me....i have my life back...a good trade off id say.

[22hamilton]

Does anyone know whether the presentations will be available to read on line, will there be one on boceprevir ?
Is the general feeling that non response to  the SOC is now thought to be genetic in nature and if so will the new PI's go some way to removing this problem. In terms of lead-ins has anyone seen non responders have a significant viral drop from the lead-in with a protease inhibitor. In my mind this is what I think I may need as a non responder.
Cheers.

[newleaf09]

On clinical care options, a site that provides continuing education for doctors but can be joined by anyone, they reviewed the current PI's and other drugs being tested.  They weren't sure if the lead-in was significantly important.  

I have downloaded the actual bocprevir slide presentations from AASLD before, think it was from the hiv/hcv advocacy site.  If you're pretty good at getting around the net, you can find just about anything.  The conference in progress now will generate tons of press and you will find places to read just about everything that is presented.  If not on the AASLD liver meeting site, then in popular press and investment sites.  Janis & friends is pretty good about posting everything and so is NATAP for popular articles.

[22hamilton]

ok thanks for that.

[banarep]

You can also go to vertex web site and listen to the presentation from last night.  it was very interesting.

[Rockerforlife]

you asked:has anyone seen non responders have a significant viral drop from the lead-in with a protease inhibitor

i went from 20 million to 6000 copies by week 4 with the SOC,then after 2 weeks of BOC it was < 15

[Rockerforlife]

BTW...in my first trial back in 2006 with SOC drugs only my VL drops were not as intense,they wnet from 24 million to 318,000 by week 4,and by week 12 it was still at 475.

[Rockerforlife]

EXPANDED AUTHORITY- The Administrator shall have authority under section 304 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 334) to administratively detain and seize any food regulated under this Act that the Administrator has reason to believe is unsafe, is adulterated or misbranded, or otherwise fails to meet the requirements of the food safety law.

[Rockerforlife]

opps...sorry....i meant to post the above post in the social side.

[Magnum]

Your comment about Boceprevir reinforces my post a short while ago, that my doctor prefers that over Teleprevir, which is said to have about an 83% clearance record. So the more I hear about the results of Boceprevir, the more I'm convinced that it will be my 5th (and hopefully) last try. I don't know how much more my body can take, but I think it can take a lot since I really work out and do all the right things....

Magnum

[mike716]

Here's my wish, Merry: That someone would finally come up with a fibrosis diagnostic that is reliable!

[copyman]

my wish is that rocker wont post so may times in one thread :-)

I guess it is time to report him again, he just don't get the hint.