Hep C Discussion Forum

mcmaklin · Senior Member

RE: Trial for people who failed DAA treatment

willbb · Member

Hello mcmaklin,

Just to add a bit to the good advice you have already been given here. Possibly to relieve your fears somewhat of Vosevi being successful for your particular situation,I have linked below a "Reviewer's Report in depth on the Pharmacology of Vosevi.

It is thick ,heavy reading ,however if you go straight to page 38 you will notice that in the last Vosevi trial (Polaris1) more than half of the 1b patients(24 of them) had resistance at the L31 position and all 24 SVR'd (100%).(page 40)

That is not surprising as L31M and V have <2.5 EC50 Fold to Velpatasvir( So basically No Resistance)

Any physician knowlegable in treating HCV would prescribe you Vosevi for 12 weeks and rightfully feel confident ina successful outcome.

There is no data that 16wks.and/or the addition of Riba would have a better outcome,however that is a discussion you would obviously have with your physician.

Good luck

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209195Orig1s000MicroR.pdf

Canuck · Guru

I would agree with Tig about your "analysis" - in regard to that this analysis notes the "substitution" to the NS5A (OMBI) at the time of this test (simply after your relapse) - it does not tell you why you failed the Viekira/Exviera.

I can only guess things about your analysis, but your doc would know how to interpret these results for you.

But in regard to your NS5A analysis - I note the NS5A (VEL) looks good for you (which works out well as you got yourself lined up for Vosevi in Oct).

If you were trying to figure out possible reasons for why you failed the Viekira/Exviera, then you would have to review any pre-treatment RAV's you may have had (when you were treatment-naive), or consider other contributory factors to the failure, of which there could be many (from non-compliance, to drug interactions, to degrees of cirrhosis, to your IL28B status (CC, CT, TT). You may never be able to figure out why you failed the first time.

I have every confidence you will be cured with Vosevi - you are exactly why, what and who it was created for.

You are lucky, in that you will soon be included in the small exclusive group of Vosevi recipients we have here - all of these people (except me) were "treatment experienced", some had been treated unsucessfully multiple times - you can search their names and read how their Vosevi journeys went. robertsamx was GT3a, I believe webtomass was a GT4, Pablito was a GT4 as well I think. I was also a GT3a. No GT1b's that I know of - but Vosevi is for ANY GT.

Here is an article that speaks about pre-existing (pre-treatment) RAVs, among other things - NS5A RAV/RAS are common - note, near the bottom it indicates the new PI's (protease inhibitors) NS3/4A's (just what VOX is) in Vosevi, overcomes much of these failure problems of the past. https://www.infectiousdiseaseadvisor.com/hepatitis/hcv-variant-resistant-to-ns5a-inhibitors-susceptible-to-protease-inhibitors/article/567033/

mcmaklin · Senior Member

Thank you - and what does it mean in the chart Ombitasvir / substitution in scored position L31M? It was a test for how drugs work for me

i hope Vosevi will work - otherwise there will be no other options?

-- Edited by mcmaklin on Monday 21st of May 2018 04:02:42 AM

Tig · Admin

The way I read that is simply that the L31M RAS (substitution) was found when you were tested. Since the substitution was found after you relapsed, it’s considered treatment emergent, or developed while you were on treatment. A NS5A RAS can be long lasting and if retreated with the same drug, it must be determined how resistant the substitution is to the drug in question, namely Ombitasvir. If you were to try treatment again with the same drugs, and it was decided the risk was worth taking, the length of treatment would have to be extended and the addition of Ribavirin in the case of Viekira and Exviera, would be required.

People relapse for any number of reasons and sometimes it’s difficult to determine exactly why, if ever. This has been a difficult virus to eradicate for many decades and they’re just now getting a handle on it. Still, approximately 1 in 10 still relapses, but they’re getting that down to half that now with the newest DAA’s, like Epclusa, Vosevi and Mavyret.

I wish I could provide you with the proof you’re searching for, but can only speak in opinions and generalities. Were I to need retreatment, I would want 12-16 weeks of one of these newest drugs. They cover all the bases, RAS’s and all and do it quite well. For now, 90-95% success rates are pretty darn impressive!

mcmaklin · Senior Member

Hello, thank you again for ALL CARE about me.

1. How many people from the forum where taking Vosevi for genotype 1b? Do you know anyone, any real-time data? If you know anyone on the forum please let me know.

2. I am trying to explain WHY Viekira+Exviera did not work for the L31M. Is it supposed not to work for this well?

3. There is a table down in my letter from my blood tests after treatment- what does it mean

Ombitasvir |substitution on scored position | 31M

Does it mean that Ombitasvir that I was taking did not work for L31M?

From my findings:

NS-3 condones covered 1-181

NS3 region (w.r.t M58335) - S7A, V48I, A66G, P86Q, K87A, P89S, F147L, V170l

Ns3 region (w.r.t H77) - I35V, T42S,T61S, R62K, I64L, S66G, V71I,I72T, P86Q, Q89S, , S91A, I132V, A147L, L153I, N174S, L175M

Resistance Analysis

Drug | Predicition | Scored mutations

Asunaprevir. | suspecitble | none

Boceprevir susbstituion on second position. 170I

Grazoprevir suspectible none

Paritaprevir suspectible none

Simeprevir substitution on scored position 170l

Telaprevir substitution on scored position 170I

NS5A condons covered. 1-104

NS5A Region (w.r.t. D90208). - K6R, S17A, L31M, L34V, L37F, G49A, Q54H, K68R, S101A

NS5A region (w.r.t. H77) I8V, E14T, S17A, K24Q, A25S, M28L, Q30R, L31M, I34V, V37F, R44K, G49A, R56T, H58P, E62Q, K68R, T71S, R78K, R81S, M83T, S85H, L101A

Resistance Analysis

Drug Prediction Scored mutations

Daclatasvir reduced suspectibility 31M

Elbasvir resistant 31M

Ledipasvir suspectible 31M

Ombitasvir | substitution on scored position | 31M

Velpatasvir supsectible none

-- Edited by mcmaklin on Sunday 20th of May 2018 10:26:53 AM

Canuck · Guru

I'm not saying that at all Mak - sorry if you took it that way. On the contrary, I am, along with many here, very excited for you that your treatment so long awaited for is imminent! I am esctatic for you! You have waited a very long time for this and deserve the best drugs. It is just a shame it had to take so long for it to come available to you (or to anyone) in the UK. I have posted to you numerous times, but these last couple times i was hoping to elicit more informative answers from you (rather than just guessing if an announcement had been made in the UK about the roll-out date) - it must be that your doc knows and has said it was so, I wouldn't know, as I have yet to find the announcement (that's all) - so we will all just assume you WILL get it in Oct, if this is what your doc is saying and has lined up. He would not be suggesting this Oct start date to you if it was not available. All I was saying is that I have not yet seen the formal announcement with the roll-out date (aside from your good news). I am very glad you added that comment about "NICE" today! That helps. It would be very good to be able post such a formal announcement for all our readers in the UK to know about - until then, we are more than satisfied to know about your planned start date in October, and revel in your good fortune to get Vosevi. I am very happy for you that you are finally going to get it, as I believe this is the very best treatment for you. Don't be confused by my posts (ask anyone round here - it can be easy to misunderstand me!) - i only mean well in my posts to you. I thought (in the absence of any formal official announcement with roll-out dates) that the info from the UK Hepatitis Trust today would be of interest to you, me, everyone here, and for any folks in the UK who may not know about it yet. smile C.

mcmaklin · Senior Member

Hello- what experience do you have here- you Want to say that inspite I have been told to come in October I may not to get it? Shall I go to a private visit for example to Royal Free? Will it help anything ? It should be available after 3 months NICE has announced it. Please help me I am confused what to do and why you are sceptic ?

-- Edited by mcmaklin on Thursday 26th of April 2018 05:46:25 PM

-- Edited by mcmaklin on Thursday 26th of April 2018 07:16:03 PM

Canuck · Guru

Hey Mak,

Just an update below (from the U.K. "Hepatitis Trust" website) - I think both you and I have signed up for their "newsletters".

Further to our exchange of posts below, where you had mentioned you might be getting Vosevi (in the UK), possibly as soon as Oct?, I have still not heard any "formal" announcement as to a "roll-out date" of Vosevi for all areas of the UK.

This excerpt from the newsletter letter today only pertains to a general announcement for Scotland, but still, a good announcement to see, that Vosevi will soon also be available to folks in Scotland. Historically, I think I have noted that Scotland had lagged behind in getting good drug choice for their people, compared to other areas of the UK and compared against other countries, so very good news for those in Scotland!

NEWS FROM SCOTLAND

We are delighted to hear that new treatment Vosevi (sofosbuvir-velpatasvir-voxilaprevir) treatment was recently approved byScottish Medicines Consortium for the following groups of people:

· Those who have failed to achieve a sustained viral response (SVR) with a direct-acting anti-viral (DAA)

· DAA-naïve, genotype 3 (GT3) HCV infection, with or without cirrhosis

Also, Epclusa ihas been approved for:

· Genotype 1 and 4 chronic HCV infection, including those with decompensated cirrhosis.

This is in addition to the earlier advice for those with Genotype 2, 3, 5 and 6.

Scottish Infected Blood Support Scheme

The clinical review of the overall impact of HCV infection will be completed by the end of May with the report sent to the Scottish Government in early summer. We are hopeful that those classed as Stage 1 (non-cirrhotic) and the families of those who died at this stage will receive the financial support that they need.

Tig · Admin

Hi Mak,

I must agree with the comments by RC and Canuck, regarding the Vosevi. It’s a pangenotypic combination of drugs that is effective across all genotypes, for both naive and treatment experienced patients. It’s effective against RAV/RAS’s, so don’t spend any time worrying about that. As Canuck mentioned, give your doctor time to make the determination of what should be included. If Vosevi is the decision, Riba is most likely unnecessary considering the extremely high rate of SVR with Vosevi alone.

Canuck · Guru

Hi Mak,

Glad to hear from you agan today!

Been wondered how you have been doing and holding up.

So, with all this waiting you have been forced to do, to get the good drug choice treatment you need from within the UK, how (specifically) has your liver been holding up over all this time??

It would help to know what your current level of fibrosis/cirrhosis is, a current Fscore: (by fibroscan and/or byblood test, something like a fibrotest or other similar blood fibrosis marker, or preferably both).

I see over on another thread today, you were saying you "might" be getting Vosevi, this coming October? That would be great!

Re the UK Trust, that I suggested for you to keep in contact with, I have been continuing to check with them for you, for any hint of when Vosevi may be coming available to relapsers in the UK. At my latest query, they still did not have a firm Vosevi roll-out date. But that would be great if you have heard that you might be able to get it in he UK as soon as Oct. smile

Boy, as I was looking for one of your own threads, on which to reply to you, I note you sure have had a lot of different threads going (over time)! It might be easier to re-read and re-review things, if your posts were more in one central area. Just a suggestion.

Being a relapser and all that does to shake a persons confidence with re-treatment, please try to keep in mind that Vosevi was DESIGNED for people JUST LIKE YOU! All our previous posts to you and conversations have been headed in the Vosevi direction, as Vosevi (in my opinion) is thee ideal drug triple for you. You could not get a better treatment for your parameters (1b and L31M).

Do not obsess on whether you are a 1a or a 1b, and whether you can read "between" the lines to connect the dots about being a 1b AND having L31M - instead, please carefully re-read the link Tig and I have sent to you and referred to in past posts - focus not on finding those two items you dwell on together in one place (ie 1b and L31M) but rather on the whole of this link - see how across ALL genotypes, across ALL RAVs, and MULTIPLE RAVs, see the success rate of Vosevi for relapsers - Vosevi holds an ASTOUNDING rate of cure. With the regime you failed on, Vosevi would be an ideal drug for you now (with or without riba). Leave the decision to whether to add riba to Vosevi, or not, up to you doc. He might, he could, as far as I am concerned, but like we have said before, the addition of riba has not been shown to improve the cure rate by much if any when added to Vosevi, as the cure rate on while on Vosevi alone is astounding (as is shown in this link!).

RAS Impact-Vosevi

-- Edited by Canuck on Friday 20th of April 2018 12:45:32 AM

Canuck · Guru

Mak,

We are not docs, we can only go by what we "think" we might know, or by reading/guessing/witnessing what has occurred in the past, or by trying to decipher the studies or docs opinions on things.

We do not know every nuance of you and your hx, or your current health. That alone makes it hard for us to figure out things/to be guessing things, everything from why you might have failed your prior treatment, to what would best ensure success on your next treatment.

Your sig line data is likely not all-inclusive or up to date - What is your CURRENT VL, what is your CURRENT Fscore (by fibroscan) or by bloodtest(s)? What are some of your CURRENT LFT's, ALT/AST/Bili? Your sig line indicates your last VL was over 100,000 aprox. May 2016, and your sig. line indicates an F score of F1 aprox Nov 2015? We do not know by what method your 2015 F1 score was determined, by fibroscan or by blood test? And we do not know what your current Fscore is, and also by what method a current Fscore might have been done. (I do believe I saw you write within one of your posts, buried somewhere in here, that you "thought" a perhaps more current Fscore was aprox. F1-2?) So, what are your firm, current VL and LFT numbers and what test method(s) have they been using in you to determine your Fscores.

Have you been having abdominal ultrasounds all along to check for of hep C signs? What are the results of your abdominal U/S's?

Since your first treatment with Viekira + Exviera, have you had any other health conditions/disease processes for which you have been on treatment for, or for which they are following in you? Kidneys disease, cardiac issues, psychiatric issues, blood disorders, etc?

Basic background info is always helpful.

___________________________________________________________________

It "sounds" as though you and your doc HAVE? decided Vosevi is the right treatment for you? Is that right, are the two of you firmly in agreement on this now?

If so, then according to you, your only other problem (other than Vosevi availabilty) is if he insists you also do riba with it, in that case he has to show you WHY he thinks you should have riba added to your vosevi, and you would need to show him why you think it should not be added (if you are reluctant to do riba, and/or do not think it will give you a significantly higher chance of cure).

My unprofessional opinion, speaking only for myself (not for you) I would not honestly be wanting to do riba with my vosevi, (nor would I have wanted riba added to any treatment I might have done!), if I could have got away with avoiding it, simply because of it's unpleasantness, and, because I do not think the data shows that riba makes vosevi that much more effective, but ... had I not done vosevi, say I only had sof/dac available to me as a GT3, and riba was strongly recommended, I WOULD have considered taking the riba, based on data. If I had other circumstances going on conspiring against me, and we decided riba would have helped me with the sof/dac or any regimen, then I would have done it.

You and your doc need to convince one another, one way or the other (add riba or not add riba).

All the studies and data, and North American recommendations we have been providing, reviewing and discussing here are not necessarily saying you must do riba with your vosevi, but we do not know as much about you as your doc does.

Take the studies to your doc, and ask him to show you his data, as to why he thinks you should add riba.

____________________________________________________________________

In the past, for other people, on dif drugs, when riba was deemed "required" to be added, there have been some extentuating exceptions made, to not use it, but generally not based on the fear of sides from riba alone - there had to be some valid contraindication, the uncomfortable sides were not as important as the value the riba would provide. Riba might be contraindicated based on pre-existing conditions, such as cardiac/hepatic issues, blood problems such as pre-existing anemia issues or other blood disorders, psychiatric conditions (being under treatment for severe psychological states), but unless you have a pre-existing pre-emptive reason for not doing riba, then you and your doc have to base your decison on whether to do riba or not, solely on the likelihood of successful cure, with it or without it.

We have sometimes seen docs ramp riba dosages upward in a graduated fashion, or downward (in response to the severity of sides like anemia say), some people have had it discontinued, many continue the full dosage for the duration of their other drugs as long as it is tolerated - it all depends on his thinking and how your body reacts to it.

_____________________________________________________________________

You are going to have to "pre"-arm yourself with facts, and have a good discussion with your doc about the pros and cons of adding riba to your vosevi.

mcmaklin · Senior Member

Canuck and Tig, Thank you very much. Please forgive me it is for me hard to accept the Riba and also I am sometimes depressed by this HCV.

1. Is there any knowledge of how much Riba I should take (my weight is 74kg) or what is the smallest amount of Ribs so it works with Vosevi? What is the smallest that there is any advantage

2. And is it OK to take it for just 2 weeks or 3 weeks and then stop, or it does not make any sense?

3. Are there possible any forever side effects after Riba with those drugs?

Thank you

Canuck · Guru

Hi Mak,

This is part of what I wrote to you earlier in the week, I'm just repeating it here again:

... PS - BTW - re: Mavyret ... Vosevi is a number one choice over Mavyret for re-treatment of a GT1 who is BOTH 5A/3/4A experienced. Vosevi DOES NOT restrict a 5A/3/4A experienced person from Vosevi use, but MAV DOES restrict a person who has had prior 5A/3/4A experience. Your prior treatment Viekirax/Exviera contained the 4 drugs ombitasvir/paritaprevir/ritonavir/dasabuvir, of which the ombi is a 5A and the parit is the 3/4A, this then makes you BOTH 5A and 3/4A experienced. The way I see it, no matter what 5A or 3/4A RAVs you may own, simply because you are 5A and 3/4A experienced person, Vosevi is your choice (perhaps with, or without riba, depending on your doc's view) ...

Now, in regard to adding riba to Vosevi? -aside from the studies provided to you thus far that were showing any significant benefit of adding riba to vosevi, and according to the AASLD guidelines, here is yet another "North American" view of the guidelines and recommendations (if you can get linked into this, to read everything within it, there you will find under DAA experienced people, the few times riba IS being recommended to add to a treatment (ie. specifically in the case of GT3's, who are cirrhotic, and who are NS5A experienced, then riba is suggested):

"CCO - Clinical Care Options - Hepatitis" -January 25, 2018 - HCV for Primary Care: Making It Easy With Simplified Guidance

Hepatitis C: Simplified Management From Screening to Cure

CME-Certified Interactive Virtual Presentation -
Terry D. Box, MD

mcmaklin · Senior Member

There is no word about Ribavirin in the place you made the quotation or I miss anythinh

Tig · Admin

I see that in your signature now. Once we start writing, the signature goes away. It's my opinion that your doctor is considering the addition of Ribavirin because you relapsed following the administration of a NS5A inhibitor. If the professional data is correct, and I have to believe it is, then Ribavirin is not indicated in your case. That's something you have to bring up with your healthcare team. Ultimately it's your decision after a conference with your doctor.

The following graphic presents the Polaris data. It doesn't leave much room for debate. The use of Ribavirin didn't provide any advantages. This is my opinion only...

mcmaklin · Senior Member

Tig - my doctor did test me for RAVs- I was sending it here. I have L31M.

Tig · Admin

Hi Mak,

I‘m going to add the official pharmaceutical information on Ribavirin at the bottom. It will simply provide you with the professional data on the drug. There is a requirement to avoid pregnancy the entire time you are exposed to the drug and (yes) 6 full months following cessation of the drug. That has been thoroughly studied and researched by the US FDA, as well as other global professional organizations.

Ribavirin isn‘t a pleasant experience. I took 1200mg per day for 7 months and I won’t lie, it was tough. It was tolerable though and the side effects tend to escalate the longer you’re on it. One thing you can ask your doctor is whether you will be taking a dose based on your weight or a lower dose, such as 400, 600 or 800mg per day. The side effects are absolutely related to the dose and time taken. You may be allowed to take a lower dose for a lesser amount of time and still obtain some of the benefit. That’s going to be a decision made by your doctor.

Your doctor seems to have some ideas, but hasn’t concluded what is the most effective route or treatment protocol. Do your research, compile a list of questions and ask your doctor to sit down and answer them. Vosevi isn’t a protocol known to use Ribavirin as part of the plan, but it has been done. If cost is a barrier, I’m not sure I follow the logic behind adding Sovaldi (Sofosbuvir) to Mavyret, even though it’s also being prescribed off label (atypical). Without going back through your old posts, I simply don’t understand why your doctors don’t simply test you for your current RAS/RAV status. Vosevi without Riba seems to be indicated in your case. I realize obtaining it is the obstacle right now, just stay on top of it and never give up.

If you use our search function at the top of the page, you can search the Ribavirin discussions we’ve had over the years here on the forum. Pay particular attention to posts by Mallani. He has presented some very good discussions on the topic.

Ribavirin Monograph

mcmaklin · Senior Member

Thank you for your care. I was talking to one of my doctors- I know I am waiting for Vosevi OR I have been told that this would be almost the same inhibitors to take Maviret together with Sofosbuvir - this could work - . but it is better to wait for Vosevi that is recommended in my case. I have been told that my Doc wants to add RIBA anyway, because wants it to be my last treatment.

We do not know if I had any RAVs prior to first treatment And Abbvie before my trial Finishes (it takes 5 years) will not say this.

At least to Start with RIBA. I am very afraid of Ribavirin as I have dry eyes, skin and I use my voice and sing. And also as I am afraid I will not be able to create music. I read some of you on Vosevi and RIva had very extreme and bad side effects. How bad could be if I take it for a month? Somebody here wrote that he was devastated. I am also affraid of psychologicall effects of RIBA (depression) and insomnia. And that it can cause long term problems when trying to have a child - are you sure that for half a year only?

-- Edited by mcmaklin on Wednesday 7th of February 2018 04:27:22 AM

Canuck · Guru

Hi Mak,

Ya know, I think you should re-read some of the info that we have already covered, right within this very thead! A lot of good discussion, and many answers to your different questions were attempted here prior. Some of it we are just repeating now. Look way back in this thread starting about Aug 26, 2016, some of the studies you are wondering about now, have already been discussed and are right there within this thread ... plus ... if you "search" the recent thread Tig mentions ALL ABOARD THE VOSEVI TRAIN , you will find some of the recent links Tig provided you there, or, if you search and re-read the thread SOF/VEL and SOF/VEL/VOX , you will find a lot of the Vosevi study data there too. smile C.

Tig · Admin

Hi Mak,

It was a small trial here in the USA, the phase 2, Triology 3 study. The participant numbers were small and really insignificant in the larger picture. We discussed it in the Vosevi Train thread. Here’s a link to the information.

Vosevi and Tx Experienced

mcmaklin · Senior Member

Hello Please, I am not able to find it, I am trying for some time already. You sent me some data that we could read that with Vosevi Trials some people with Genotype 1 had worse results with cure than those who did not take ribavirin? This is about Voxilaprevir. And that Riba does not make much difference.. Please.

What are you relating to?

"Tig has brought you up to speed again (in the re-presenting/re-reading of the old vosevi trial data) - with and without riba - and, he has already re-reviewed the good data we have already posted on the site in regard to how many relapsers with RAVs come to vosevi for very successful re-treatment, so I won't keep going there to that subject matter,"

-- Edited by mcmaklin on Tuesday 6th of February 2018 08:32:45 AM

Canuck · Guru

It is not available in UK yet (as you know) and it is not yet available in Australia either (as far as I know).

Australia may get it first, OR maybe the UK will get it first, no one knows at this point. But I am guessing these countries (UK or Aus) may get it long before you will find a generic version coming available out of India.

I am simply letting you know where I think you would likely get it the soonest. C.

mcmaklin · Senior Member

Thank you - I wrote to HepcTrust and am on their mailing list.

By the way - obviously I hope to get it soon in UK, but why you discourage to receive medicines from India when they become available - let us say from Natco or Mylan?

And the second question - I cannot see any way to get it from Australia, how?

-- Edited by mcmaklin on Thursday 1st of February 2018 02:32:15 AM

Canuck · Guru

Mak,

Further to my post below, I queried the HepC Trust via their on-line helpline. They said they are "waiting" to hear, waiting to find out when vosevi will become available in the UK. They indicated they "hoped soon". On further query, additionally they offered they also did not know yet "which type of patient" will get it.

You (as far a "type") being 5A/3/4A experienced, should qualify for vosevi.

The last time I checked for availabilty of vosevi in Australia, they were in the same "waiting" boat as the UK. Australia was waiting for vosevi, (and, also waiting for Mavyret as well?). They had hoped availability in Aus. would happen in 2018.

Should vosevi become available in Aus. (sooner than in the UK), then that gives you another country from which to try to source vosevi. One would think Australia would be receiving vosevi sooner than waiting for generics to start to become available (out of India as you had mentioned).

As we discussed prior, the best bet is to get vosevi from the country you are in, as I do not see obtaining vosevi by generic route happening anytime soon.

When it is not available in the UK, then the next quickest option is to look to the countries who ARE offering it to their own populations and see if you can get it there.

Canuck · Guru

Hi Mak,

Tig has brought you up to speed again (in the re-presenting/re-reading of the old vosevi trial data) - with and without riba - and, he has already re-reviewed the good data we have already posted on the site in regard to how many relapsers with RAVs come to vosevi for very successful re-treatment, so I won't keep going there to that subject matter, I could just repeat a lot of what I said in my last post to you below (Nov 25), or from older posts that Tig and I and others have exchanged with you in the past but i will just stick to this instead ...

You are in UK, your doc is in UK, and you say you cannot get vosevi UNTIL you can access it generically out of country??

Are you sure about that? I would suss this, for sure, as access could be your largest impediment affecting your long term planning.

(Perhaps more so than anyone's focus on your 5A RAVs, or on your TT status), I am rather firstly concerned about your "access-to-vosevi" problem.

WHY do you and doc think you will not get vosevi in the UK SOONER than getting it via a generic route out-of-country?

Did you try to sleuth the UK Gilead contact I directed you to (from the Nov 25 post below), to see if anyone there could answer you about how soon you might be able to access vosevi in the UK?? I'll post it here again (below), it could be a useless dead end, but if I was having difficulty getting vosevi, being told I cannot get vosevi in the UK anytime soon, and if I were you, I would like to hear that from Gilead themselves, and to be able to ask them ... if not now, then when.

Contact address:

Gilead Sciences International Limited
Flowers Building
Granta Park
Abington
Cambridge
CB21 6GT
United Kingdom

Or, have you tried to seek info from any other Gilead contacts via any of our other Gilead links that are already found within our website here? PAYMENT ASSISTANCE PROGRAMS All Gilead contacts listed in there are Canadian or USA contacts I believe, but perhaps they can link you better to someone for specific info about the vosevi situ in the UK.

There is also the UK resource Hep C Trust ( http://www.hepctrust.org.uk/about-us ) to inquire with about how soon vosevi may be available in the UK. C.

PS - BTW - re: Mavyret ... Vosevi is a number one choice over Mavyret for re-treatment of a GT1 who is BOTH 5A/3/4A experienced. Vosevi DOES NOT restrict a 5A/3/4A experienced person from Vosevi use, but MAV DOES restrict a person who has had prior 5A/3/4A experience. Your prior treatment Viekirax/Exviera contained the 4 drugs ombitasvir/paritaprevir/ritonavir/dasabuvir, of which the ombi is a 5A and the parit is the 3/4A, this then makes you BOTH 5A and 3/4A experienced.

The way I see it, no matter what 5A or 3/4A RAVs you may own, simply because you are 5A and 3/4A experienced person, Vosevi is your choice (perhaps with, or without riba, depending on your doc's view).

-- Edited by Canuck on Tuesday 30th of January 2018 04:44:26 AM

Tig · Admin

Here’s some reading material that should reinforce your decision to seek Vosevi. There shouldn’t be any concerns regarding the L31M location.

RAS Impact-Vosevi

mcmaklin · Senior Member

Hello, for now my only option is to wait for Vosevi from India.

I have some more news though to remind you:

I am 2 years after failed Viekira+Exviera Genotype 1b. Do you think I need a Ribavirin? I assume Vosevi will be good for me and will work for this L31M

From my findings:

NS-3 condones covered 1-181

NS3 region (w.r.t M58335) - S7A, V48I, A66G, P86Q, K87A, P89S, F147L, V170l

Ns3 region (w.r.t H77) - I35V, T42S,T61S, R62K, I64L, S66G, V71I,I72T, P86Q, Q89S, , S91A, I132V, A147L, L153I, N174S, L175M

Resistance Analysis

Drug Predicition Scored mutations

Asunaprevir suspecitble none

Boceprevir susbstituion on second position. 170I

Grazoprevir suspectible none

Paritaprevir suspectible none

Simeprevir substitution on scored position 170l

Telaprevir substitution on scored position 170I

NS5A condons covered. 1-104

NS5A Region (w.r.t. D90208). - K6R, S17A, L31M, L34V, L37F, G49A, Q54H, K68R, S101A

NS5A region (w.r.t. H77) I8V, E14T, S17A, K24Q, A25S, M28L, Q30R, L31M, I34V, V37F, R44K, G49A, R56T, H58P, E62Q, K68R, T71S, R78K, R81S, M83T, S85H, L101A

Resistance Analysis

Drug Prediction Scored mutations

Daclatasvir reduced suspectibility 31M

Elbasvir resistant 31M

Ledipasvir suspectible 31M

Ombitasvir substitution on scored position 31M

Velpatasvir supsectible none

Tig · Admin

In the recent past, after Sovaldi (Sofosbuvir) was developed, Gilead made sweetheart deals with pharmaceutical companies in Asia (India, China) to market generics of those drugs. They balked at first because as we know, Gilead and Big Pharm in general, wanted to limit or deny access rights to these manufacturers once they made it known they were going to reverse engineer the drugs. They don't have the same patent right obligations we have in the US and UK. So instead of fighting these countries over a battle they would likely lose, they made a deal with them to manufacture and market these generics, as long as they gave Gilead a cut of the profits. That's a simplification of the deal, but you get my drift. Even with these agreements, Gilead has continued to try and control the exportation and importation of these drugs to different parts of the globe. If the rogue (?) pharmaceutical manufacturers want to copy Vosevi, they'll have a fight with Gilead when they do. They can still do it, as long as they don't export it. It's a practice they have done in years past. That is a common reason some people take medical junkets to foreign countries. You can fly in, get treatment and come home. Sometimes you can come home with the medication, but risk having a banned or prohibited substance confiscated on arrival by Customs. If Gilead doesn't agree to the same deal they have with other drugs, their patent rights extend over a decade on some of these medications.

Hope this answers your question.

mcmaklin · Senior Member

Could you Please clarify? I do not understand - is anything worse to get than it was?

Unless Gilead cuts a deal with the generic manufacturers in Europe and Asia, I think it will be years before we see it.

-- Edited by mcmaklin on Saturday 25th of November 2017 02:35:42 PM

Canuck · Guru

Mak,

Well, thanks for straightening me out about what country you are in, and from what country you were treated prior, and from what country (now) you are currently seeking vosevi from. That helps, as that info has always been a little confusing for me (from many long ago posts) when we had you in Poland and assumed traveling to UK for consult with a special doc), that is until now, when you have nicely clarified what your current country is. (Your country is/was not in your bio).

Announcements of fast-tracking mavyret and vosevi for approval came out first in the EU (before North America). The UK (as many countries are) struggle with budgets to fulfill their health systems. Despite the vosevi approvals I have no idea where vosevi is really at in the drug budgets of the UK. No idea if Brexit plays into how well or when vosevi is going to "get going" in the UK.

I'm thinking, surely you, being in the UK, and having a doc there, and having access to helpful informational via UK health websites, would have a much better idea whether vosevi is going to be easily available to you there, soon or when?

I tried to look things up, for you, (from here - Canada) but I cannot make a lot of (your local) international/UK websites display for me.

What does your doc say to you??!!(About vosevi availability). What have you found out from him, or, on your own, from inquiring within the UK about the reality of vosevi availablity in the UK??

From our prior exchanges, you do have youth and a low F score on your side. BTW - what ARE some of you VLs, LFT's, recent fibrosis assessments (since May 2016), and as far as I can recall both you and your sister had HCV since birth (?) or, since earlier in your youth anyway, and subsequently your sister was successful in her HCV treatment, but you unfortunately relapsed after your late 2015 treatment (if I have that right) ... so then, how many years do you estimate you have been HCV+?

As I mentioned long ago, perhaps one of your impediments was your TT status (aside from the obvious that you are finding it difficult to get access to, and lined up for vosevi). Access to vosevi may prove to be the larger impediment. (As a layman) I agree with you though, I would think the triple vosevi would be best for you, taking into consideration ALL the info that we have shared with you (within the old posts) - namely the RAVs studies done before and after in pts who were treated with vosevi (and perhaps adding riba to it if your doc thought it useful). Altho Mavyret (even as a double alone) is garnering good results as being very pan - (I'm sure you and your doc have tried to compare your particular RAV's against glec/pib performances, just as you compared your RAV's against sof/vel/vox performances)? Without trying to re-visit Mavyret performance again (in relation to your RAV's), I still am partial to vosevi (but mind you, I am merely a layman and vosevi prejudiced too).

Like I said, I can't crack into many of the UK websites for info - here is just one - not very riveting.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004350/human_med_002153.jsp&mid=WC0b01ac058001d124

(Note under the "authorization" tab - a local UK Gilead address).

Tig · Admin

Unless Gilead cuts a deal with the generic manufacturers in Europe and Asia, I think it will be years before we see it. The patent dates have been extended out over a decade preventing the legal release of any authorized generic.

Vosevi generics [nope]

mcmaklin · Senior Member

Hello, I am living in UK. I only had clinical trials in a different country.

I believe VOSEVI is the right option for me. Are there ANY news it WILL be available in generic versions, or is there a possibility it will not be?

thank you

Canuck · Guru

Hi Mak,

Glad to hear from you again.

In your country, have you already confirmed that vosevi (as a "rescue regime") has not been approved (in principal) for use???? And that it won't be, in the near future???

It would be best if vosevi was offered to you, in your country, by your country. If you have already exhausted EVER getting vosevi in your country, and you are thinking you can source it elsewhere (out-of-country - ie. India or UK that you were asking about) - there are people who can help you buy your own drugs out-of-country, but, as you are probably already aware, vosevi (sof/vel/vox) is not yet being sold like that (out of India). One can source epclusa (sof/vel) but not vosevi (yet), certainly not that I am aware of. And it may take quite some time before vosevi can be sourced this way, perhaps even longer than we saw it take for sof/vel to come out of India.

You have had a prior trip and physical consult in the UK with a UK doc there, (but unless you have dual citizenship, for your country AND for the UK) then I am not understanding the logistics of how you would be able to get a doc in the UK to prescribe and treat you with vosevi (even if the UK system chose to give a pt vosevi as a first choice). Have you re-checked with your "doc contact" in the UK again, about your wish to recieve vosevi treatment from him?

UK, Can and US have all had vosevi technically/officially "approved for use" but that does not necessarily mean the citizens of these countries will get it (even if the pt. is convinced that vosevi is the best rescue regime for them). Many variables/restrictions/conditions/limitations could apply, and residents of those countries may still be offered dif drugs first.

Whether it be UK, Can or US, it has really been only quite recently that citizens of these countries have been a bit more successful in more easily being offered even things like epclusa (even tho the epclusa approvals were fast-tracked and the approvals have been standing for quite some time now) people are still being offered lesser or dif regimes first. I can see the same thing happening with vosevi, although approved for use in a country, people may be slow to receive it. (ie. In the US, with vosevi being approved for use, and then rolled out available in August, I have still found it impossible to find out how many US people have actually been successful in obtaining their vosevi by prescription).

I do believe it will be quite some time yet before an out-of-country vosevi-like generic will be available for purchase. It will likely follow the same pattern as we saw happen with epclusa. I think the in-country roll-out use of vosevi is slow (maybe will be even slower than epclusa was), and that the out-of-country development of a vosevi-like generic version will be slower still than the out-of-country generic epclusa development was.

Good you have had your RAVs re-checked, and it's good that vel is not on your list of no-go's.

You can double-check with AUS people like Greg Jeffreys and Dr. James Freeman and the "fixhepc" people, or with that nice fellow Nirav Sangoi, about when they think out-of-county vosevi-like generics might be coming available.

Aside from Gileads vosevi, I have not heard of any other pharmaceutical companies making any announcements about their own vosevi-like formulas being made available for sale soon. As well, I believe Gilead was just successful in having some of their licensing extended to something like the year 2023(?), so events like these may have a bearing on generic dvelopment. Gilead seem to have control of vox/vosevi right now.

I do not think you will find a source for out-of-country generic vosevi-like formulas yet, anywhere. There has been talk of "Beacon" and about 4 other pharmaceutical companies exploring development of generic vox, but I do not think their generic vox will be sold seperately. I believe their generic vox will be sold (just as Gileads formula is), as a triple formula, an "all in one" pill, of sof/vel/vox.

Dr. Freeman has had at least 4 dif Redemption "trials" that have been occurring over time (accessed via "fixhepc"). They had various drug "trials" - this one, "Redemption Trial #4", was only for epclusa (sof/vel) - https://fixhepc.com/r/root/redemption/4

You can check resources such as Greg Jeffreys/Dr. Freeman to see if they have any plans for further Redemption "trials", specifically a vosevi one - I have not looked lately, but I did not see them offering a vosevi Redemption "trial" via this route as yet.

If you do get vosevi, it will just be up to your doc whether he thinks the addition of riba would benefit you further, or not.

That's all I can think of for now, if I hear anything else, I will of course let you know. C.

-- Edited by Canuck on Friday 24th of November 2017 04:44:40 PM

mcmaklin · Senior Member

Is there VOSEVI available in UK? Or I should wait till the release it in India (any news?)

As you know I am 2 years after failed Viekira+Exviera Genotype 1b. Do you think I need a Ribavirin? It is important to me.

And maybe you can tell me more about those findings:

Thank you

From my findings:

NS-3 condones covered 1-181

NS3 region (w.r.t M58335) - S7A, V48I, A66G, P86Q, K87A, P89S, F147L, V170l

Ns3 region (w.r.t H77) - I35V, T42S,T61S, R62K, I64L, S66G, V71I,I72T, P86Q, Q89S, , S91A, I132V, A147L, L153I, N174S, L175M

Resistance Analysis

Drug Predicition Scored mutations

Asunaprevir suspecitble none

Boceprevir susbstituion on second position. 170I

Grazoprevir suspectible none

Paritaprevir suspectible none

Simeprevir substitution on scored position 170l

Telaprevir substitution on scored position 170I

NS5A condons covered. 1-104

NS5A Region (w.r.t. D90208). - K6R, S17A, L31M, L34V, L37F, G49A, Q54H, K68R, S101A

NS5A region (w.r.t. H77) I8V, E14T, S17A, K24Q, A25S, M28L, Q30R, L31M, I34V, V37F, R44K, G49A, R56T, H58P, E62Q, K68R, T71S, R78K, R81S, M83T, S85H, L101A

Resistance Analysis

Drug Prediction Scored mutations

Daclatasvir reduced suspectibility 31M

Elbasvir resistant 31M

Ledipasvir suspectible 31M

Ombitasvir substitution on scored position 31M

Velpatasvir none none

Tig · Admin

Hi Mac,

RC is right, Vosevi is mentioned as the initial recommendation with Maviret a suggested alternative. The advantage of a 3 drug regimen is it hits three links in the chain. All you have to do is effectively break the cycle of replication at any point. The subject on RAV/RAS is complicated. If a particular variant is resistant to one drug, it may be susceptible to another drug in the combination. That's the benefit of a multi pronged approach NS3/4, 5A & 5B protocol.

robertsamx · Guru

Once C sees this post you can bet she will research my question and get back with a answer. I looked and couldn't find a RAV"s report. RC

robertsamx · Guru

RE: Trial for people who failed DAA treatmentMav

mcmaklin · Senior Member

RE: Trial for people who failed DAA treatment

Tig · Admin

Hey Mac,

Thanks for posting that resource, it's a good one and comprehensive. Just looking at the information briefly, it would appear to me that they are recommending 16 weeks of Maviret as a good option for you. It will take some additional reading to fully grasp all of that data, but they're getting closer to figuring out this RAS dilemma.

mcmaklin · Senior Member

Hello, thank you again.

I just found: www.hcvguidelines.org/evaluate/resistance

Please tell me what is going on, I have genotype 1b and L31M after treatment with Viekira+Exviera.
WHY all those articles like this here say about L31M ONLY in case of genotype 1b? What is the difference between L31V and M here? Is Maviret or Vosevi good to kill the L31M but in genotype 1b where there were non trials?

thank you!!!

Tig · Admin

The pangenotypic tablet includes the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir. It lacks the NS5B inhibitor. It is still very effective without it. They call it Pangenotypic, it is good for all genotypes.

mcmaklin · Senior Member

Because my Doc was doing many times Abbvie trials so may get drugs as a gift before it is founded. I was taking part in Viekira+Exviera Trialas. My Doc has no chances for this with Gillead

what inhibitor lacks in Maviret?

robertsamx · Guru

I second that Tig. MCM may want a second oppinion. RC

Tig · Admin

I've never heard of such a thing. If cost is a factor involved in prescribing Vosevi, why would they consider adding Sovaldi (sofosbuvir) to Maviret? That would raise the cost by approximately $87,000.00 US for 12 weeks. Abbvie remains in conference about what Maviret's asking price will be, but it won't be cheap. None of these treatments are inexpensive and regardless of whom pays the cost, it's a huge amount of money and it impacts distribution.

I provided an explanation about the 2 or 3 drug combos and why 3 drugs may perform differently in my last post. If your doctor wants to add Sofosbuvir to Maviret, why not just prescribe Vosevi? You need to get a second opinion.

Canuck · Guru

Hi again mcmaklin,

Nice to hear from you - we haven't heard from you in a while! - I can see you and Tig (and RC) have "gone deep" into RAV's and the "what will I/what should i end up with" for treatment again.

This is a good thing to do, to try to keep abreast of all the possibilites. It must be immensely frustrating not be able to have all therapies available to you or offered to you, and the waiting involved. So many people (TN and TE) are being so easily/quickly cured nowadays, I know you are happy for them, just as you were for your sister's success, but still, this must feel a very long unfair haul for you.

In reviewing the many posts we have all shared together over time - we keep hoping to hear that you are imminently being offered a good treatment. Maybe you are now closer with the likes of the newer Abby and Gilead doubles and triples that have or are coming to the fore.

Have you been doing ongoing searches of all the trials all this time? Didn't you or your doc see any Abby glec/pib trials over there (or in the UK), at any point? Did you and your doc follow the Merck ruz/uprif/grazo trials?

I do recall you bringing this up long ago (about your doc mentioning some combo of adding Gileads sof to Abby's glec/pib), and I do "vaguely" recall something like that, but I could not find that particular sof use, nor did anyone else I think (back then at that time) - there was no solid ref. of a study to where sof was added to glec/pib. Easily found however, was riba being tested out added to glec/pib in Abby's older trials - but Abby went to market heavily touting how effective/pan Maviret is, with a special emphasis on it being "riba-free".

I like the theory behind triples, but I do not like riba much as a third or added drug tho! Especially palatable/acceptable are all the "new" NS5A's, NS5B's and 3/4A's that have come out or are coming out nowadays (as doubles OR triples) that are riba-less. The new drugs are becoming very competitively effective, very pan, more effective, powerfully proven to work well for TE and in many cases very close for TN alike.

The efficacies data IS in the trials, you just need access to the drug choices!, and then, your work-up "re-done" for your doc to select and confirm the best regime for your re-treatment.

Man, I hope a doc (in UK OR home country) can find you access to your best drug choices. When was the last time you saw your doc to ask about getting Vosevi (or another regime he feels would be the best for you)? Keep banging on the doors, in UK and home, one IS going to open, soon I hope. C.

mcmaklin · Senior Member

Long time ago I heard my Doc wants to add Sofosbuvir to Maviret? Is it the third medicine that is lack in Maviret combo comparing to Vosevi? Have you heard about such a combination?

Tig · Admin

The repeated RAV testing is kind of a waste until you're ready to start treatment. The RAV's you mentioned, the L31M (common) and Q54H (not so common) are both susceptible to current drugs, but you have to remember, these new drugs are coming at us regularly and one never knows what will be offered next or with what. That's why testing for RAV's now and waiting 6 months or a year to treat serves little purpose. NS5A/B RAV's are long term, but nobody really knows how long term. Could be a year, could be five, don't know. What they can tell is what drugs are more effective and what isn't against not only the virus, but resistance profile to existing RAV's. If during the year wait, one of these variants should disappear or weaken, then your options might change.

Basically, you're right. Vosevi and Maviret are both very effective treatments. Given adequate exposure to either of the drug regimens, I'm confident that you will kill the virus. Remember what RC said about the tire spokes? If you had zero RAV's, then it wouldn't matter how many spokes on the wheel you removed, it would stop the virus from replicating. Since you do have two known RAV's at this time, using a drug regimen that attacks 3 spokes instead of Maviret's 2 spoke attack, your odds theoretically should be better. "Should" is the key word here. Like I said, they are both good regimens and both appear to be recommended for you at this time. If you can obtain Maviret, I certainly wouldn't turn it down. All you have to do is have one of the drugs do it's job and the virus will cease to replicate. You must expose yourself long enough for the drugs to work and even though you have an RAV that will cause some "resistance" to the treatment, it doesn't mean it won't work. If it said "prevents" the intended drug action, then for sure you wouldn't want to use it. They can tell the strength of a particular RAV and the likelihood of success given a certain protocol. Your doctors should be able to ascertain the correct drug regimen and protocol for you quite easily once you are ready to start.

This can be terribly confusing for all of us and I wish I had a perfect explanation for you. This stuff is complicated, but we're learning about it all the time. I'm confident that with the proper testing at the the correct time, it will allow your doctors to determine the best regimen for you. A good specialist will steer you in the right direction. When the opportunity presents itself, and your doctor recommends a particular regimen, do it. You have to place trust in your doctor. Together we can offer discussion and debate here, which will give you the chance to ask some knowledgeable questions. If you aren't getting the right answers, then you have to make a decision based on that. The new DAA's are quite effective and if you take them long enough, you're going to win the battle. I'm pretty sure of that....

mcmaklin · Senior Member

Tig - this is interesting - so what exactly lacks in maviret? Not so good Ewa because I may get Maviret faster. And the more I testes RAVs twice another time a year after treatment and I have still L31M The use of the new triple, Vosevi is popular because it attacks the virus on three

-- Edited by mcmaklin on Saturday 19th of August 2017 05:07:41 PM

Tig · Admin

Mac,

You might like to read this as well. Maviret is a good option. The use of a NS3/4 PI (Vox) wouldn't be advised in people with decomp. cirrhosis, but that won't apply to you anyway. Maviret doesn't require Ribavirin either. The use of the new triple, Vosevi is popular because it attacks the virus on three planes. The resistances are mitigated by their strength and by the addition of other drugs. Using RC's spoke example, all you need to do is destroy one spoke and the virus can't replicate. Provide the proper length of drug exposure and you block the virus ability to replicate. Once undetected your immune system takes over and keeps it that way. If the two dugs in Maviret can provide that, you achieve SVR. The train of thought right now is relapsers (in particular) have one extra drug in the Vosevi combination. Instead of a two spoke attack, you have three. Kind of a basic analogy but it works...

Drug Combo's: Who will benefit?

Hep C Discussion Forum

Contact address:

Legal Disclaimer: