Isiscat2011 wrote:

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Very exciting stuff.   It really makes me wish I could roll back the clock on my HCV/liver disease.  I'd just sit back and let the pharma guys show me what they can do.  It is a seller's market now but that will change.

I don't know if most people really appreciate how much better HCV tx is still going to get.  What Malcolm and Matt have mentioned is the future: Individualized tx, Short tx durations, and 100% SVR rates for all genotypes (especially easier for those who are not carrying a bunch of tx induced mutations).  

 

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 It is exciting!  To think of 100% cures and even shorter treatment times, wow!  I hope John is reading this, he really needs some encouragement today. 

Very exciting stuff.   It really makes me wish I could roll back the clock on my HCV/liver disease.  I'd just sit back and let the pharma guys show me what they can do.  It is a seller's market now but that will change.

I don't know if most people really appreciate how much better HCV tx is still going to get.  What Malcolm and Matt have mentioned is the future: Individualized tx, Short tx durations, and 100% SVR rates for all genotypes (especially easier for those who are not carrying a bunch of tx induced mutations).  

My tx duration with HARVONI will be twice what it would have been had I not treated previously.  Six months instead of three.  Getting it right the first time should be the goal for anybody fortunate enough to be able to wait, IMHO. 

Hey Malcolm

At the AASLD convention this week my friends from the Texas Liver Institute (Dr. Lawitz) will be presented a LB-33 (Late Breaking) abstract on almost that very combo. Very powerful DAA combo, this will tell us a lot of if its possible to treat HCV in a much shorter time frame.

C-SWIFT: MK-5172 and MK-8742 + Sofosbuvir

In treatment-Naïve Patients With Hepatitis C Virus Genotype 1 Infection,

With and Without Cirrhosis, for Durations of  4, 6, or 8 Weeks,      A total of 102 patients were enrolled.

They will present complete SVR4 data, and SVR8/12 data for the short duration treatment arms.

matt

Hi all,

On the subject of RAV's, remember they are only specific to one particular drug. In the AbbVie combo, the most likely culprits would be ABT-450 and ABT-333. These block the most unstable viral sites, particularly in Geno 1a's.

Hopefully the individual RAV's will be identified in AbbVie's submission to the FDA, and then we may get some info on how long they persist.

The Merck drugs should get a mention. MK-5172 is probably the most effective antiprotease and seems to block the protease site of all Genotypes.

I see Gilead is spending more money trying to develop an antiprotease and a non-nucleoside NS5B blocker. Why? They are already testing their new NS-5A blocker, GS-5816. This will be co-formulated with Sovaldi to make a pan-genotype treatment. Why spend money on antiproteases and non-nuc's'! Drop the price of Harvoni instead.

IMHO, a combination of MK-5172, Daclatasvir and Sovaldi would cure 100% of all genotypes.

I saw that you relapsed on a prior AbbVie trial, Matt, that's a shame.    I'd certainly be wanting Harvoni too in your situation.  I'm sure you know (much better than I do) not everyone is going to achieve SVR on any treatment.  I feel like the odds are in my favor and I have the best chance with this combo, but if it turns out this doesn't work for me, I will just have to try again later.  My nurse mentioned I should get a new toothbrush, razor, and nail clippers so as to not re-infect myself.  Perhaps they had you in mind when they said that?

To Isis's servant,  I like honest discussion.  That's the only kind worth having.  I don't want to come off like AbbVie's designated spokesperson, I just want people to feel like the have some other really good options for treatment, because I do believe this is the case.  I am scared some people might sink into depression because they can't get Harvoni.  I do value Mallani's opinion more than anyone else's on here, for sure.  Isn't he a doctor or something?  I hear what he's saying.  But again, I have to go with the odds on this one.  Free treatment doesn't hurt either.  I have high-deductible insurance and should soon have two sons in college.  That $4,000 deductible would hurt not only me, but my ability to help them financially.  Also, all these drugs are just taking their baby steps out into the world, and I don't think we know what any of them are likely to do 10-20 years down the road.  We might grow a 3rd eye for all we know.

Vanessa, you got to do what you think is right for you, when it's right.   It can be very stressful to change jobs, especially a long-term one like you had prior.  A stressful environment probably isn't the best one to go through treatment in.  When the time is right, you'll know.

That's the thing, justvlm: Sometimes there is more than one solution to a problem and the solutions are equally reasonable. Given your specific situation you do have options and you selected a reasonable one that is right for you.  We do need to monitor our health closely when we decide to delay tx (especially our liver health) and the longer we have had HCV the more important this becomes.

I'm glad you will be meeting with a new hepatologist.  I have always believed that the single most important HCV decision we can make is finding the right doctor: one who is well informed, has HCV tx experience, is open to discussing options, and will fight for us if need be.  Good for you.  

This is a very excellent topic.  I have turned down the AbbVie Trial as I was feeling that I was jumping because it was a financially great opportunity, even with the Riba arm possibility.  And that was it!!!!!    If I wasn't about to start a new job that will require me to 100% focused ~ maybe, but I was getting the strong gut feeling that now is just not the time.

  I may very well live to wish I had jumped on it with all my toes and fingers -I will meet my new hepatologist in a few weeks.  I will trust that my health has maintained and the best treatment for me will cure this dragon.

I can't thank you guys enough for bringing a ton of digestible information to peeps like me.  I sure have never gotten this from a doctor.

Matt Chris wrote:

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"Here is a summary of the resistance profile at the time of Post-Treatment relapse for Subject XXXXXX that we can provide: There were no emergent, resistance-associated variants detected by population-based sequencing in the virologic failure (PTW4 visit) specimen for this subject."

Also in reading a abstract that was published in the NEJM regarding this Trial they also disclosed that of 208 participants in the 12 week arm 12 patients relapsed and only 2 had no Rav's detectable at relapse, of course I was one of the two.

 

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Just crunching some numbers here and in this particular study ~94% SVRd on the 12 week Abbvie combo.  Of the 12 relapsers ~83% had tx associated RAVs.  Do you know how long those RAVs may last, Matt?  Any studies on whether Harvoni can knock them out?  Just out of curiosity how many of these were tx experienced, cirrhotics?

In your situation, with no Abbvie RAVS, it seems like Harvoni would be a no brainer.  I expect once your doc explains all this to the payer you will  see some positive movement.

Very useful information, Matt.  I am thinking that in the near future docs will have some tx prescribing choices to make, and being well informed will certainly be in our best interests, because not all docs will have studied this subject so closely.  It may take some time for AASLD guidelines to catch up as well.

We know that insurance companies will want to pay for whatever is cheapest (assuming comparable SVR rates) but that doesn't mean we will have to accept a protocol that is less desirable for our specific circumstances even if we have to appeal an initial decision.  I am just prognosticating here but I'm thinking that since Harvoni will probably be less expensive for 8 weeks than Abbvie for 12 that both Harvoni and Abbvie will need to be on ins. co. formularies (despite Express Script's threats to exclude Harvoni).  In 2015 docs will likely have some other options on the table.

We should continue follow the specific tx options (including duration) closely.  Patients' individual needs should be considered and they will vary widely.  

Hey LC & Isisicat

I can shed some real world light into this exact conversation about AbbVies Combo ABT-450, ABT-267, ABT-333 with Ribavirin.

I was on AbbVie's 12 week Turquoise II HCV trial ( Patients w/cirrhosis)  from Jan 2013 thru May 2013. I fortunately relapsed EOT 4 weeks, there is agreement with all four of the doctors (hepatologist, ID) that I consulted on that in my case I needed 24 weeks or I was possible re-infected via personal grooming item (Toothbrush) after trial ended. 

More to the important point regarding Rav's, at the time of my relapse. I wanted to know this info. because it is very important in choosing treatment in the future. I hounded ABBVie for 11 months and right after the 2014 EASL conference in April they finally disclosed via email my details, you will see them below.

"Here is a summary of the resistance profile at the time of Post-Treatment relapse for Subject XXXXXX that we can provide: There were no emergent, resistance-associated variants detected by population-based sequencing in the virologic failure (PTW4 visit) specimen for this subject."

Also in reading a abstract that was published in the NEJM regarding this Trial they also disclosed that of 208 participants in the 12 week arm 12 patients relapsed and only 2 had no Rav's detectable at relapse, of course I was one of the two.

So LC knowing the cause of your relapse can be important, but you have great odds in your favor to achieve SVR so most won't apply.

The ABBVie protocol was for me mostly ok, I had some incidents of grade 3-4 of Billirubin labs which the trial doctor handled poorly but other than that it was very tolerable.

matt   

I hear you, LC, and in your shoes I probably would have made the same choice, and it certainly isn't my intention to question anyone's past decisions; just to let those faced with these decisions know they have options.  It is such an individual decision and for me the factors would also include how long I had the virus (if I knew), my age, any other health-conditions, lab results, and of course whether I had any hepatic or extrahepatic symptoms, etc.  

I like to give people their options because I know health care professionals are not discussing the nitty-gritty details of life post-tx if the tx is not successful.  It can have long ranging effects including fewer future tx options, fewer clinical trial options, more difficult access to tx, and potentially even long term health consequences.  I think people have a right to have all the relevant info when they make their choices.  

I would encourage everyone to read Malcolm's take on the Abbvie combo as well because he understands the science better than anyone.  He indicated that tx failures will be very low, but they could be "disastrous" in terms of RAVS.  That doesn't mean it isn't a great combo for what is available now.   

Like I said, I know this is a touchy subject, and believe me I don't like saying it (people get mad at me!).  But, I feel strongly about patients having access to all sides of the story.  It is devastating to feel you have not been told the truth when things don't work out the way we had hoped.  For most people treating HCV with all-oral DAAs is a no-brainer; it is worth the risk.  But, there are so many different people in so many different situations out there.  I just don't want patients to feel like someone else has made their decision for them without telling them all the facts.

P.S.  We are fortunate to even be facing these potential choices.  Many people around the world will have far fewer options in their near futures. 

Isiscat2011 wrote:

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I agree, LC, and I'm really hoping that people can also be realistic not only about access to treatment, but also the nature of tx itself.  HCV tx is not perfect but it will improve over time.  

I understand the feeling of urgency to tx HCV, and for many people, the need is urgent and the possible benefits clearly outweigh the potential risks. But, understand that this is not magic; it is imperfect science.  There will still be relapsers with the current tx.  The consequences of failed tx can be substantial and life altering.  It may effect your tx options in the future.  In the future there will be tx drugs that will kill the "wild type" virus 100% of the time in a relatively short period of time (perhaps even a single injection).  Controlling RAVs may not be so easy for those who have failed previous DAAs. This needs to be at least considered by those who have time on their sides.    

I have said before that if I could afford to wait for a few years, until we really see how these new drugs hold up in the real world, and until tx gets even better I would.  I know this isn't a popular thing to write but being realistic is a good thing, IMO.  There is a difference between being proactive and reactive.  

Realism: the attitude or practice of accepting a situation as it is and being prepared to deal with it accordingly.

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I remember debating with myself on whether or not to do the peg-interferon based rx, but I am glad I was able to wait.  It is tempting to take what you can get, just to hopefully put it all behind you.  I know it's these medicines aren't literally magic, and there is a reason it's called "practicing medicine".    True, failed treatment will have some real consequences, just as waiting too long can have some real consequences as well.   I figure I've had HCV for 30 years, and I'm thankful to be getting treatment before substantial damage sets in.

Another thing I want to point out (again) if you are like myself, a treatment-naïve genotype 1a, the AbbVie combo actually has the best clinically efficacy rates for us, with even better than Harvoni - per Gilead's own information.  So if you are like me, and you don't take a ton of meds, want your best shot at cure, keep that in mind.  We don't have to turn into "vampires" and avoid the sun on the AbbVie combo either.  

I agree, LC, and I'm really hoping that people can also be realistic not only about access to treatment, but also the nature of tx itself.  HCV tx is not perfect but it will improve over time.  

I understand the feeling of urgency to tx HCV, and for many people, the need is urgent and the possible benefits clearly outweigh the potential risks. But, understand that this is not magic; it is imperfect science.  There will still be relapsers with the current tx.  The consequences of failed tx can be substantial and life altering.  It may effect your tx options in the future.  In the future there will be tx drugs that will kill the "wild type" virus 100% of the time in a relatively short period of time (perhaps even a single injection).  Controlling RAVs may not be so easy for those who have failed previous DAAs. This needs to be at least considered by those who have time on their sides.    

I have said before that if I could afford to wait for a few years, until we really see how these new drugs hold up in the real world, and until tx gets even better I would.  I know this isn't a popular thing to write but being realistic is a good thing, IMO.  There is a difference between being proactive and reactive.  

Realism: the attitude or practice of accepting a situation as it is and being prepared to deal with it accordingly.

Hi Guys:

I read that a more realistic expectation is 3 years--and that is just for treating HCV patients who are already diagnosed.  To eradicate HCV (in the USA) will take decades (longer if we don't get the RAVs problem under control).  Not a huge surprise though.  So much for the health care free market system.  Part of the problem is the fear based idea that the Affordable Health Care Act (Obamacare) and other measures that could help citizens equal socialism.  

If the USA knows how to do one thing best--it is propaganda.  Scare the people into believing they will be living in some kind of dystopian socialist nightmare so unrestrained, greed infested, Capitalism can thrive.  This is just the tip of the iceberg.  Millions have already lost their homes, their pensions, their life savings, and their health to the American dream.  The unaffordability of life savings drugs should serve as a wake up call for those who need to be personally impacted by it to believe something exists. 

Hey LC

Nice work, after reading those two articles it again makes us see that we are in this window of waiting, setting in, adjustment of the insurance part of the equation. The first waved of patients will have to endured this period anyway they can, I know after waiting myself for what seems like a long time, the reality is the bean counters at the Ins. companies just are not going to jump at our request to spend over $100,000 without a battle.  I guess its going to take 6-12 months (Unfortunately for many) for all the different staged patients to resolved into a treatment protocol.

I guess this is how free enterprise in a non government controlled drug price system works or should I say doen't work. With Obama care we all are edging toward socialism so perhaps the Government will step in on the issue of how high is to high on drug cost, really when you think about medicare its that way already in some aspects.

matt       

I want to start a thread to talk about this because from what I am reading, there are a lot of people who probably aren't going to qualify for Harvoni (I hope that's wrong), and a lot of insurances are probably going to try to stall to see if they can go with a more affordable option. 

http://www.medpagetoday.com/InfectiousDisease/Hepatitis/48282

http://www.fiercepharma.com/story/express-scripts-ready-favor-abbvie-hep-c-prospect-provided-it-undercuts-gil/2014-10-31

The most expensive medicine may end up being reserved for the sickest people.  Like someone said in another post, insurers can't afford to buy everyone a $200,000 house and stay in business.  Everyone wants the best treatment they can get for themselves, that's just our survival instincts kicking in, and no one should feel bad for worrying about their own options. 

There are people who have had severe reactions while on prior treatment to Ribavirin, and that's completely understandable that you want to avoid it on your next treatment, but I also have to wonder how much the other drugs like Interferon, teamed up to make the side effects that much worse?  Also, I would imagine the length of treatment may play a large factor right?  If you are F3/F4 or even a null-responder on a prior Interferon based treatment, hopefully you can jump to the front of the line for Harvoni.

I'm not to discourage anyone from trying to get Harvoni, of course!  I just want them to feel like they have some other viable options, and to be encouraged by the effectiveness of the other drugs that should be getting FDA approval soon.

http://www.realendpoints.com/wp-content/uploads/2014/10/Harvoni-Press-Release-Slides.pdf - where the slides came from

http://www.marketwired.com/press-release/move-over-gilead-abbvie-could-bring-serious-competition-to-hcv-market-1956910.htm - article that explains a bit on how this chart is scored

Not to keep beating this same drum, but I am worried for those of us who aren't that sick, who aren't going to get approved, who aren't sliding in under the door before other likely less expensive treatments hit the market.  I want them to have hope! 

If not Harvoni, there's AbbVie; if not AbbVie, there's Merck; if not Merck, well you get the idea...   God willing, we are all going to get to SVR and soon.