TOPIC:

Me too Sir, Me too.
M

You are so optimistic guys.
Put me on the right thinking path.

Thurl

Two implications for responding to relapse may arise from Prof Gane's comments.

1.
would an option for a relapser be to go on permanent, lifelong sofosbuvir

In theory I don't see why not. It was tried with interferon for people most at risk to go on a permanent maintenance dose. That was not very successful, but with sofosbuvir it might be. The dosage and the safety of taking sofosbuvir for more than 24 weeks would have to be determined though.

It might be relevant to mention here in passing that most of the damage to the liver is not actually done by the virus itself. It is done by the immune system setting up inflammation in response to the virus, which eventually results in scarring of the liver. So the goal of a maintenance therapy should be to damp down the inflammation response. However if most of the virus is destroyed by the sofosbuvir then I imagine (but I'm not totally sure) that that amounts to the same thing. Anti-fibrotics is another interesting area for maintenance therapy. Doesn't seem to have made very much progress so far but worth watching.

2.
But if the defective ledipasvir, while not effective enough to cure, is effective enough to give rise to resistance then the unfortunate patients will truly have had the worst of both worlds

Nobody likes to think about relapse but it happens. When it happens, resistance is left behind. Those are the facts. I think you might as well forget about the defective ledipasvir not giving rise to resistance. Even if it didn't, the sofosbuvir still would. Retreatment is a topic about which not very much is known presently. Testing people to analyse their particular crop of RAVs may come into practice, so that they may be better targeted. Or maybe Gilead's next drug, velpatasvir, will be strong enough to plough through all the types of RAVs regardless. I think that is their idea but we'll have to wait and see.

I would most welcome any comments on either of the above questions. I am genuinely worried.

I think that everybody must worry about the tx not working, even if defective drugs are not involved. I know I do. There are no assurances for that particular worry. It used to be much worse when people failed interferon and nothing more could be done for them. Nowadays with the DAAs, for people who can access the available drugs and medical help, things have never looked brighter. We are just about at the event horizon in hepc drug development, which is the point at which if you fail then there will always be something else along in time to keep you going. I think that's about as good as it gets.

Footnote:
Regarding drugs that are hard to make, you can be sure that Gilead has learned the lesson and will ensure that their future drugs are diabolically hard to make. So it's a good job that the Chinese are diabolically clever.

dt

Still so sad that a respected doctor/professor didn't take the trouble to actually test anything and just offers his possibly justified opinion. Again I ask Prof Gane " simply show us your science!"

REDEMPTION will answer the question. I would not bet against Mesochem being vindicated of Gane's insinuations.

I haven't seen anything in this thread that covers much ground that wasn't covered previously. Prof Edward Gane is a brilliant and well respected Hepatologist and researcher. He was instrumental in proving the efficacy of many of the DAAs that are now available and my understanding is that also includes many others than those patented by Gilead.

As to why he isn't proving the efficacy of generics? Why the hell would he? That isn't his job! He already has quality, proven DAAs that he was involved in the proving of and so has confidence in for his patients and others to use around the world.

What you guys are doing is asking the developer/tester of a Mercedes (which is admittedly priced like a Rolls-Royce) to test and prove and state that a Honda is just as good!

I will state this again: -

If you do not want world leading and professional Medical experts involved in researching and proving new medications, then don't expect many major breakthroughs in the future!


Okay end of

On the other subject of using Sofosbuvir as a prophylactic until something else comes along, probably not.

The "nuke" that Prof Gane is referring to is indeed Sofosbuvir which is a "Nucleotide analog". It is fairly unique in the way it operates as it effects the HCV virus at two points. This does make it fairly immune to resistance but not totally so. So long term use as is being proposed could result in resistant strains developing.

As others have commented, we can currently retreat by hitting the virus with the same meds longer and harder, or we can test for what the resistance is caused by and then select an alternative DAA that acts on different pathways. Or failing both those options we probably need to wait for a new drug to be developed that will be effective against our resistance strain. But that is happening fairly regularly these days as we understand better and better how HCV works and what is needed to stop it.

Don't take this the wrong way but......sometimes when I read this forum I think people could be forgiven for thinking the DAAs cause certain individuals to LOSE THEIR FUCKING MINDS!

I'll come to that in a moment. First to the question of using DAAs prophylactically. I asked this some months back here . You can read the doc's response for yourself.

Now as to Professor Gane. The doc commented on that here . Please read it again. Here are some more of James' comments about the Prof. I think some of you may have misinterpreted his response. Prof Gane, as far as we know, is not the enemy, is not being disingenuous, is not trying to scare the bejeezus out of everybody.

In the words of Tom Robbins, the enemy is dullness of mind.

This is like the whole Seymour thing all over again. And look at how well that ended. Lost ourselves one good source of information there.

My guess is no one's tested to see if the Mesochem drugs are bioequivalent because that level of reverse engineering may not be possible. And in a post that I can't find from the doc, IIRC he said it may not even matter if they are not exactly bioequivalent.

Bottom line, the Mesochem APIs might not work (my understanding is Incepta are just combining them to make Twinvir). In the same post I can't find right now the doc points out there are good reasons to believe it will all be ok. Moreover, Mesochem is a big company and have a considerable reputation at stake. It would not be in their interests for this whole thing to go belly up.

Nevertheless, the drugs might not work. They might not work because they are not bioequivalent to the proprietary medications. They might not work because sometimes even the proprietary drugs don't work. Here's something to worry some more about if you feel you must. These drugs have been fast tracked. Nobody knows for sure yet what the long term effects may be.

As John Lennon said, "life's what happens when you're busy making other plans."

Worrying is just gonna make you sick not better. And that's dumb because there's sweet FA that any of us can do about the situation beyond what we've already done.

Look good people, in all likelihood, you're going to be cured. Really you are. But maybe you won't be. You won't know until you know. But please don't waste your time fretting over something that hasn't happened yet and that you can't change even if it does. As far as relapsing goes, what I've been told is that if you hit it again harder, you almost certainly get it the second time around. So the odds of not being cured keep getting smaller. What's more, if you said to me 10 years ago that within a decade we'd have drugs that would cure most cases of HCV, I'd of laughed in your face.

But here we are.

Likewise, as has already been pointed out, better and better drugs are on the horizon. But nothing in life is certain. Ever. In the meantime, all you can do is.........



Oh and in regard to this....

Blimey. Enkel, I know the man in question he was Geno type 4 Pre treatment
and post treatment he was Geno Type 3 his consultant same as mine explained it too me.

Geno type mutation is not unheard of!

I could be wrong, but I think it is unheard of. Mutations of genotype into a more resistant strain of the same genotype, yes. Mutation of one geno into another, I don't think so. My bet would be this person has gotten reinfected with a different genotype.

My opinion:

Dr. Freeman posted a link concerning Twinvir and other Generic medications.

The chemical evaluation is that Twinvir at least is identical to Harvoni.

So Gane's can say whatever he wants. It does no mean he is right.

But Gane's has some affiliation with Gilead, my affiliation is with Dr. Freeman.

So I say try the generics first and save your $92K for something more beneficial to YOU.

How many of us already purchase Generic Medications from our local pharmacy's because they are cheaper they all have to be tested.
So are these meds we are taking for HCV.

Like I said, REDEMPTION will settle this. I don't have any cards on the table because my last 8 weeks were Harvoni. BUT, I think generics played a huge role in forcing Gilead to makes its "deal" with Australia, because they saw the handwriting in the wall. I still believe the best way for them to combat the generic movement is to sow doubt about their efficacy. If Gane had made his remarks 4 months ago, where would we be now? If I could have found one negative comment about Mesochem products from a reliable source, I wouldn't have been mixing them on my dining room table. It can't be any harder for Gilead to test generic ledipasvir than it was for the Chinese to duplicate it. Gilead has alot more to lose from generics than Mesochem has to gain from them.
I believe the Chinese product is just fine. I believe Gane when he said that led is far more difficult to make than sof. So, what has changed?
Nothing.
Mike

Prof Gane is obviously a very smart fellow, and sometimes people with big brains like that just say whatever is on their minds without really considering the social implications. I doubt it occurred to him that it might upset people. And really its fair warning, because although I am totally confident about the Mesochem meds and FixhepC, there are most certainly dodgy meds out there. People do need to proceed eyes wide open. Knowing that Led is hard to make is useful info, because it means you know to look harder at whether the source would be capable of producing them.

I think the chance of not getting a SVR is a real concern for us all - AND would be if we were taking Gilead's products as well.

What I am seeing in the signatures though, is 'so far so good'.

I remember people worrying about VR=UND and expect as treatment ends, there will be a focus on SVR and we will hear more from people around the SVR testing dates.

My own storey to date is all good and I hope it stays that way.

Some things cross my mind:

a) My liver was f....'ed over big time prior to treatment
b) the generic DAA's over three and a bit months have been a dream ride compared to the one month or so of crap endured with interferon etc.
c) if the generics fail, then they have bought me quality time with my family and daughter.
d) refer to a. above - prior to generic DAA's I was running out of time. MY specialist told me "the next stop for you maybe a transplant'.
e) refer to c. above

As for this forum, never met a better bunch, it's just a pain that adversity brought us together.



Yours


J.

On the other subject of using Sofosbuvir as a prophylactic until something else comes along, probably not.

The "nuke" that Prof Gane is referring to is indeed Sofosbuvir which is a "Nucleotide analog". It is fairly unique in the way it operates as it effects the HCV virus at two points. This does make it fairly immune to resistance but not totally so. So long term use as is being proposed could result in resistant strains developing.

Gaj - I don't think resistance would be a problem because a cocktail of drugs would be used in a maintenance regime, each countering the resistance of the other, as is done with HIV.

I'll come to that in a moment. First to the question of using DAAs prophylactically. I asked this some months back here. You can read the doc's response for yourself.

Yes you did bring up the topic Chester, and it is a good one. While the doc put forward options that he would prefer, I think that it's good to have all options on the table and scrutinized to the depth that satisfies those still curious, if possible.

dt

Do we all not have enough things to worry about???????
I am sure everyone here worries whether it is working or not ? Will I be the one that does not reach SVR?
The "What if's" are endless,,,,,,,
I appreciate that there are many unknowns regarding the path we have taken but would you rather be worrying about the time you may have left to live without doing anything,,,,,,,,
There are many who are sailing through their treatments, but I think there are a lot more who are "fragile" and do not need any additional fears added.
And "YES", I do understand that discussion/questions help us to understand/learn more about this shitful virus we are fighting but I am more concerned about scaring people without evidence.
#RANT over (I hope my banana appeared)

BTW- I am week 13/24 Sof/Dac and 4 months ago, I could not have strung 3 words together, let alone a post in a forum! The clarity is amazing and I can put up with the aches and pains as long as I am able to think and concentrate. I read every day but I usually don't have enough time to post.
I sincerely want to thank all of you for letting me be a part of your experiences and you have all helped me in one way another just by telling your stories
Best wishes to you all for your treatment.