PIs versus SOC

Welcome to the world of spin.  A place were small eggs are large and large eggs are giant, small coffees are tall, triple A rated bonds are junk and women’s dress sizes are steadily growing.  February home sales rose says the NAR while they actually dropped 23%. Vertex says the results are great and the lawyers say they are not.

So – in this brave new world, how can you tell what new drugs are going to be worth waiting for?  Well – not without much more work that you want to put in.  I encourage everyone to look at the study released by Vertex and look at the lawsuit.  Are they comparing RVR stats between SOC and triple therapy?  Did Vertex withhold data or did they release it at the conference when they were first allowed to.

Are protease inhibitors in combination with SOC more effective than SOC alone?

Interferon and Ribaviron do not attack the virus directly; interferon stimulates our own immune responses to attack the virus while Ribaviron makes the virus unstable and causes it to mutate more rapidly than normal.   This approach is comparable to firing a 12 gauge shotgun at a mosquito; you have a good chance of killing it, but you will hit many other things along the way.

A protease inhibitor is designed to hit the virus directly and miss everything else.  It rarely achieves that goal, so side effects appear because it has impact on other cells within our bodies.  That is what caused the first PI, BILN, to be withdrawn.

Because the PI hits the virus directly, it quickly lowers the viral load by killing everything not resistant to it.  This leaves a small number of virions  for the SOC drugs to kill and making it much more likely that they will be eliminated in significantly less time.

Does that mean you should wait for the new drugs?  The answer is maybe.  The answer is dependent on whether you can afford to wait based on your biopsy result, your genotype and your predicted response profile: age, race, body density …et al.

Interferon is a very dangerous drug with serious side effects.  Here is an old warning label:

Warnings and Contraindications
Anemia associated with the use of REBETOL in combination with interferon alfa-2b (REBETRON Combination Therapy) may exacerbate symptoms of coronary disease or deteriorate cardiac function. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated. The most common adverse experiences associated with REBETRON Combination Therapy are “flu-like” symptoms, such as headache, fatigue, myalgia and fever, which appear to decrease in severity as treatment continues. Severe psychiatric adverse events, including depression, psychoses, aggressive behavior, hallucinations, violent behavior (suicidal ideation, suicidal attempts, suicides), and rare instances of homicidal ideation have occurred during combination REBETOL/INTRON A therapy, both in patients with and without a previous psychiatric disorder.

And this before they discovered that it can cause psoriasis, arthritis and many other auto immune diseases – not to mention thyroid malfunction.   I believe that anything that reduces the time spent on interferon is worth it.

I am very biased towards PIs.  It appears to have worked for me after 20 years of battles.  You need to make your own decisions.  I mean this post to be a starting point.  No one should take what I say at face value.  I am not a doctor or scientist though I have tried to be as accurate as possible.

[dranurag]

Dear andiamo 1

The drugs really look promising but interferon is not as bad as you think. all adverse effects are reversible when you stop it. However I am intersted in PI .Are they available? By what name ? I am from India.

[Andiamo1]

Many of the adverse effects are not reversible.  There are plenty of people that have permanently damaged their thyroid.  Having taken interferon for 7 out of the last 20 years, I can tell you that it is devastating on the patient and the family.

They are only available in drug trials at this time, since none are FDA approved as yet.  I am not sure what the status is in India.

[moahunter]

I also think interferon is not that bad, and feel that Ribarvirin is the nasty one in the mix. That is to some extent what concerns me about the additional mix drugs.

To me, there is a fundamental difference between Hep C and HIV and that is, that many people with Hep C decide not to treat, that the side effects outweigh the benefits. Whereas with HIV, people feel they have no choice.

Accordingly, I think there will be the most benefit overall, if more people can be convinced to treatment. To that end, the focus should be on reducing the side effects of existing treatment, while looking for replacements for existing treatments, rather than add ons (which may scare away more people). In this respct, I think Albuferon could be absolutley briliant, and that similar drugs are the best way to go, along with research into some form of other future treatment not involving Ribarvirin or one day, interferon(vaccine or similar).

[moahunter]

Another way of puting it, if tommorow we had the choice between:

1. An add on drug that will raise success rates to 90% for those who can stay on treatment; or
2. A replacement for existing treatment with minimal side effects, but only a 40-50% success rate,

IMO 2 would save and improve the lives of far more people than 1. With minimal side effects, there would be far fewer dropping out of trials as well.

[moahunter]

Another way of puting it, will PI's just lead us to an HIV type blind alley - being that of maintaining a low viral count, or controlling the virus, while needing to constantly change treatment due to mutations - good for Pharmaceutical companies I guess, as many different drugs get rotated. A blind alley for Hep C I fear, because unlike HIV, many Heppers can live without virus maintenance, and hence, won't lower their standards to accept the side effects.

[Andiamo1]

Where did you hear that PIs lead to a low viral count when used with HCV?  All the studies show that SVR is SVR and RVR is RVR no matter if PIs are used or not.  There are plenty of Prove 1s that have been SVR for over a year now.

I see one of the world famous Docs and he couldn't disagree with you more about the desirability of continuing with SOC drugs.  I have own experience to go by: I treated for 7 out of the last twenty years and the impact of that was devastating on me and my family.  I had to do it, since I was progressing rapidly to stage 4 and by treating repeatedly, I was able to maintain stage 3 since 1992, with very little progression.

I think we both want the same thing: a cure for this disease that helps a large percentage of people.

As far as your choice  1 and 2, I certainly agree with you about 1 being optimal.  

[Forseegood]

I've heard this debate so many times here...there is the "interferon is the worse offender" crowd...then there are the "riba is the bada$$" bunch... me thinks that you wouldn't want to date either one of them, lol...but you gotta go with what we have...I personally think these trials are taking too darn long, but I guess that's the process...probably that Vioxx fiasco didn't help matters with FDA processing...I asked the renown Mstermeet to come on here and talk on this, cause I remember him having more knowledge of the trial participants than just about anybody on here...

but he's off having a life I guess, cause I haven't heard from him...lol....great points on either side of the debate...but, as I've said before many times..., some things fall into the "many different aspects" realm, and it's almost impossible to make it a black and white, right or wrong, issue....there are just too many variables.  

But like I've said before, just from the sampling of trial participants here, it gives me hope for the PI's...many of the current posters weren't here when you guys were all on here together, reporting your results...I tried to pay attention, but alas, I don't remember everything...HR says the ultimate cocktail would be the polymarase, PI's, together...wouldn't that be grand? hope so anyway....

One thing though, Andiamo, for having treated soooo many times, youre still as sharp as a tack...that gives me hope too....

[Ironduke]

First of all, congratulations on finishing up your last treatment.  I really pray you reach SVR.  To go through 6 or 7 rounds of treatment is amazing.  You have been an inspiration to me when I was going through just one!

I also elected to go through a trial of a PI (Boceprevir) with SOC and I am glad I did.  I don't know yet if I will achieve SVR but I was UND by day 14 of treatment so I have a good shot.  Maybe I would have been RVR without the PI, but I certainly think it was a major contributor.  Interferon is nasty stuff, I think the less you are exposed to it, the better.

I agree that in ideal world we would have treatments without either Ribaviran or Interferon and the side effects they bring, but I don't see that happening anytime soon.  I think the PI +SOC or some other combination with SOC will be an interim step until we get there.  The data so far suggests it will be an improvement over SOC, at least for geno 1.

Ironduke

[susan400]

waaaahhhhh   I just want to clear.....   Susan

[desrt]

Interesting article about why VX950 may be the exception to the rule on earlier PI failures.

http://www.****/17713156

I knew BILN2061 wasn't "the first PI" and found this googling.(O.K. maybe the first pushed heavily to market.)
I still believe drug "cocktails" are more appropriate to DNA retroviruses like HIV and chronic HBV than to an RNA virus like HCV, but as you pointed out I'm no biochemist and opinions are cheap.
If VX turns out to be an useful tool in the fight, I'll be leading the cheering section. I have too may non-responder friends not to.
The jury is still out and hopefully this will become as academic a question to you as it is to me.
SVR to all.

[Andiamo1]

Unless I am mistaken, HCV is a retrovirus and AIDS is an RNA retrovirus.  I just googled them both and found articles that back up that idea.

[desrt]

Just differentiating between RNA and DNA types. Interesting that MedHelp edited part of my link. I wonder if it's pubmed or nih they don't like.

[Andiamo1]

I meant to say that both AIDS and HCV are RNA retroviruses.

[viaduk]

As a relapser, if  tomorrow I was offered a triple combo that would give me a 90% chance at SVR,  I'd be polishing my tx  body armor for another battle.

[desrt]

Not to pick nits, but HIV really is a DNA lifeform making it much more similar to HBV than HCV. Otherwise we'd be seeing AIDS patients and people with HBV using riba as part of their med mix.

[Andiamo1]

I am not willing to argue with you over this.  You might benefit from doing a Google search on HIV and read about it for yourself.  HIV is an RNA retrovirus and not at all similar to HBV.  If you find less than 100 articles on the net that back that up, I will be surprised.

[moahunter]

"Where did you hear that PIs lead to a low viral count when used with HCV?  All the studies show that SVR is SVR and RVR is RVR no matter if PIs are used or not.  There are plenty of Prove 1s that have been SVR for over a year now. "

Was a bit busy yesterday. This is essentially what has happened for HIV patients, because the disease mutates. One combination of PI's might work today, they have to move to another tommorow.

Hep C is a different disease. If PI's can increase the initial hit, and eliminate the virus with the assitance of interferon and ribarvirin before mutations can occur (unlike with HIV). That is great. In this respect, PI's have promise, and will hopefully help many people. But it is pretty clear to date, that PI's need interferon and Riba, on their own, they cannot provide enough hit.

The problem I have with the cocktail is the way to go approach, is as I stated above, HCV is very different in that many people choose not to treat. Making the treatment harsher, with more sides, even with greater sucess rates, may not convince more people to treat. It will help those who have made the decision to treat, and want to clear, but what about the bulk of people out there, who have already decided, that treatment is not worth it, even with the current sides?

To me, I really hope the ultimamte solution is a replacement for Interferon and Ribarvirin, not another cocktail drug. Until a PI comes along that can do this, or there is a suggestion that this will happen, I think other lines of research need to be focused on too. In particular, I would like to see more work on reducing the sides of existing treatment, advanced forms of interferon, and vaccines, and other alleys.

[moahunter]

PS. I talked to my specialist briefly about this too - she is a virologist rather than a heptologist (due to initial concerns over what disease I might have contracted). Her big hope she told me, was of a vaccine, that eliminates what this treatment puts people through. There is vacine work going on ( eg. ChronVac-C), it the immune response can be stimulated enough eventually, that would be the best of all worlds IMO. Hope we get there!