Downsides of Daclatasvir

[Jorah]

I was looking at some articles about Daclatasvir/Daklinza ( I can't find them now) but it said something like: If you fail treatment with daclatasvir, the virus mutates to the point that other antivirals won't work. (or something like that)
Has anyone heard about this? Does this happen with other meds or is it a trait of daclatasvir?
I was considering treatment with it but now I'm worried.

Thank you kindly

[KimInTheForest]

Hi Jorah. Excellent question. It got me looking, partly because I had also read that ledipasvir (a component of harvoni) can lead to resistance if one's first harvoni attempt is not successful.

So this is what I found:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961994/

Basically, all of the first generation NS5A inhibitors (which include daclatasvir and ledipasvir and some other things) can result in resistance to other first generation inhibitors. At least as I read it: if you fail at daclatasvir, it may not be useful for you to then try harvoni because they each contain a similar first generation NS5A inhibitor.

However, it looks like the second generation NS5A inhibitors, which include Gilead's GS-5816, are better (but not perfect) at avoiding the resistance problem. You can search clinicaltrials.gov for "GS-5816" to see if there is anything coming up you might be eligible for. I was very interested in finding a GS-5816 trial. But then this opportunity to be part of the harvoni trial came along, and it seemed too good to refuse, since the exact same trial in New Zealand netted a 100% cure rate for tx-naive Geno 3s.

good luck!
kim

[Jorah]

Its a little scary , but thanks so much for the info Kim. I wonder when GS-1518 will be available on the market, who knows maybe 2 years...
I talked to my Hep Docs about the Harvoni study the one you mentioned and they're not convinced, they feel its a very small study and maybe a variant of geno 3 over there...etc etc and thats why they're (Gilead) doing now the study you're on to see if they can reproduce the 100%.
My Doc said that daclatasvir is being approved this week in Ontario and they have high hopes for grazoprevir/elbasvir also G3. They also say within 2-3 years we will have more drugs.
Thanks again you're always such a good source of information and help. 

[KimInTheForest]

Good luck with it Jorah. It can be a dilemma alright about whether to leap now with what is available through trial or prescription or wait for "something better" to come along.

My understanding about the Harvoni/Riba trial for geno 3s is that there has also been one in the US, which had a cure rate above 90% (maybe 95%) for tx-naive geno 3s. And that the reason they do one in each country is as part of the approval process for each country. But it is true the NZ study with the 100% cure rate was just based on 26 people in that arm of the trial. Not large.

best,
kim

[Jorah]

I spoke with Gilead,  they are trying to package Sovaldi/GS-5816 with a protease inhibitor to hit most Genos that is still in the works, they don't have a date for that maybe 2 years. But in November they're looking to move in GS-5816 packaged with Sovaldi if not by November for sure by March.

[KimInTheForest]

Good to know, Jorah. Good work checking with Gilead.

kim

[Debula]

I am posting here to follow this post as my husband is a geno 3 and we were waiting for that new drug to be approved because his doc doesn't want to give him riba
Thanks for the info guys!

[KimInTheForest]

My personal feeling is if you are Geno 3 and have access to Sovaldi+Daklinza (daclatasvir), it would be worth it to go that route. Chances are very high that you will be cured. So the "resistance" issue is not terribly relevant when the cure rate is so high. Also, even if a person is in that unlucky 5% who doesn't get cured, and does perhaps develop resistance, there is so much in the pipeline right now, that there will be another chance before long at something new that will get around the problem of resistance.

Having just gone through a 12-week treatment myself (and pretty sure it worked), my current feeling for anyone with Hep C is: if you have access to a new treatment (especially a short 12-week treatment) that has a super high cure rate and does not involve interferon, just do it. There are so many others who would give anything to be in that position right now. It is a blessing.

cheers,
kim

[Jorah]

Yes Kim, I think you're on the right track with the thinking, I rather have the 24 weeks if I can, I just think that having it (virus) for such  a long time may need some extra time.
With you finishing the 12 weeks how do you feel?

Out of curiosity when you go on a trial, who provides the meds? Does your pharmacy dispense them or you get a shipment in bulk from the company. Who tests your blood and follows you, your own Doc ?

Thanks again

[KimInTheForest]

Hi Jorah. Today is my 10th day post-tx, and it is the first day I have started to feel good (but not spectacular). The ribavirin anemia took a toll on me, and it will take a while for my hemoglobin to rebound. This is the first day that I have had something approximating normal energy and mental functioning, and decent mood and attitude. I am VERY eager to experience my new life once the anemia is resolved. I had a taste of it in my early weeks of treatment, when the virus was wiped out but the anemia had not yet kicked in - and it was GREAT! I had energy and mental clarity and eagerness and 'aliveness' like I have not had for years. So I think that was a glimpse of what my new life will be like once the anemia resolves.

As for trials, you won't get your drugs directly from a pharmacy. And your local doctor is unlikely to be the person monitoring your progress unless he/she is also the one running the trial (or one of the study groups for the trial). Trials and trial participants are really closely monitored. My study group was based at a liver centre in a large city. So I travelled out of town to that liver centre for all my check-ups and blood tests. Nothing else would have satisfied Gilead's requirements for monitoring. The liver centre gave me my drugs as well, 4 weeks' worth at a time, although i went more frequently than 4 weeks for all the blood tests. Each time I went, I had to bring my pill bottles and have the contents counted and recorded to make sure I was following protocol.

Each time my blood is collected for labs (Day 1, Week1, Week2, Week4, Week8, Week 12, EOT-4 weeks, EOT-12 weeks), the lab results fill 30 pages! So they are running a lot of tests for trial purposes and research purposes beyond the most basic that a prescribing physician might order if you were simply being treated for Hep C. The consent form I had to sign was 20 pages, and it would have been 40 pages if it involved an experimental drug. Harvoni is no longer experimental. But something like GS-5816 would be.

kim

[Jorah]

I love to hear that part when you say : I had a taste of it in my early weeks of treatment, when the virus was wiped out but the anemia had not yet kicked in - and it wasGREAT! I had energy and mental clarity and eagerness and 'aliveness' like I have not had for years.

I crave that, all these years I always wondered if the low energy  was just me or it had to do with the hep or maybe I’m just getting old. 

I’m glad you’re feeling better, it must be not easy, they should invent a machine sort of like an aquarium air stone that oxygenates your blood.  Maybe having an oxygen tank at home and wearing periodically will help?   LOL

Thanks for the info about the study, I remember years ago a company shipped me several bottles of a natural product for free , part of a study to determine if the stuff was good, I think it was called hepatico from some Russian Doc. (didn’t work for me) But what did help was Chinese herbal medicine it took care of this low grade fever sensation that I had.

Talking about Daklinza I just noticed that article of of the coinfected on the front page about Sovaldi/Daklinza… interesting. Successful but they were all on antiretroviral therpy together with Sovaldi/Daklinza.

Thanks for sharing the info, later   

[Debula]

Hi Kim / Jonah
Kim I am so happy to hear you are starting to get your energy back
I wish I had a glimpse like you did but sadly, I was exhausted before and still am
Maybe I always will be   But my liver is pretty bad so that might be the reason.
Hopefully once I am cured maybe . just maybe my liver function will get a little better.
Johah I feel you-I crave that too!  I too thought it was about getting old or a thyroid condition that I have which also causes fatigue and mental fog

So I just read that it is FDA approved! http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm


The doc gave him (my husband) and appointment for November in hopes that daclatasvir will be FDA approved by then. YAY he was right!  Now I wonder how insurance will handle this.

Here is something from the artilcle

" The safety and efficacy of Daklinza in combination with sofosbuvir were evaluated in a clinical trial of 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection. Participants received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks and were monitored for 24 weeks post treatment. The studies were designed to measure whether a participant’s hepatitis C virus was no longer detected in the blood 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s infection had been cured.

Results showed that 98 percent of the treatment-naive participants with no cirrhosis of the liver and 58 percent of the treatment-naive participants with cirrhosis achieved sustained virologic response. Of the participants who were treatment-experienced, 92 percent with no cirrhosis of the liver and 69 percent with cirrhosis achieved sustained virologic response. Daklinza labeling carries a Limitations of Use statement to inform prescribers that sustained virologic response rates are reduced in HCV genotype 3 infected patients with cirrhosis."

And here is a link from Bristol-Myers Squibb
http://news.bms.com/press-release/fda-approves-daklinza-daclatasvir-treatment-patients-chronic-hepatitis-c-genotype-3

YAY! off to check and see if our insurance covers it!!

Be well
Deb

[Westy]

It's an old thread but my response may be relevant for some. As you can see in my signature I did a BMS peg/Riba trial in 2011 and didn't respond, they pulled the Daclatasvir out at about week 6 when I stopped responding. I am now into week 8 of Sof Dac Riba regime that will hopefully knock it on the head. The path messed up the VL test at week 6 so now waiting for result and expecting UND at week 7.

The prior use of Dac and resistence was a consideration but thankfully it appears to have worked. First V/L went from 19 mill to just 16 in 14 days so i;m in the game.

cheers

[Gaj]

Hi All,

Yes, oldish thread but perhaps a bit of extra information about resistance.
My, admittedly laymans, reading of the literature is that while restistance to one NS5A inhibitor may result in resistance to another, it will depend on how the resistance is expressed via the enzymes/links involved. So while resistance to Dac may result in resistance to Led (and/or others) and also the reverse.....it depends!
So tests would be required to determine which enzymes/links were causing the resistance and then hopefully choose another inhibitor that operates slightly differently.
But as always, seek expert advice for your own particular situation.

Gaj