Is Epclusa superior to Daklinza for Geno 3?

[Jorah]

Hello There,
Seems that the Doctors at my Liver clinic have held back patients from going on daclatasvir/Sof and they prefer them going on epclusa. Does anyone why? I didn't have a chance to ask them...one of the nurses mentioned quickly that with daklinza if it doesn't work the first time it inhibits a chance to repeat with sovaldi...or something like that. LOL

Thank you kindly

[Lynn K]

Per the current AASLD treatment guidelines they are equally recommended

http://www.hcvguidelines.org/full-report/initial-treatment-box-summary-recommendations-patients-who-are-initiating-therapy-hcv

Genotype 3 Treatment-Naïve Patients Without Cirrhosis - Recommended
Recommended regimens are listed in groups by level of evidence, then alphabetically.
 
Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) for 12 weeks is a Recommended regimen for treatment-naïve patients with HCV genotype 3 infection who do not have cirrhosis.
Rating: Class I, Level A
 
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) for 12 weeks is a Recommended regimen for treatment-naïve patients with HCV genotype 3 infection who do not have cirrhosis.
Rating: Class I, Level A

[Jorah]

Thank you Lynn 

In the same link that you sent me I noticed that treatment for those with compensated cirrhosis, the treatment with Epclusa stays the same (12 weeks same dose) but for the Daklinza/sofo they double up the time 24 months and add ribavirin. Which make me conclude that Epclusa is more powerful. They're not sure if I have cirrhosis they think I'm F2 depending on what day I take the liver scan, a month latter they thought I was F3

Genotype 3 Treatment-Naïve Patients with Compensated Cirrhosis‡- Recommended
Recommended regimens are listed in groups by level of evidence, then alphabetically.
 
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) for 12 weeks is a Recommended regimen for treatment-naïve patients with HCV genotype 3 infection who have compensated cirrhosis.¶
Rating: Class I, Level A
 
Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) for 24 weeks with or without weight-based ribavirin is a Recommended regimen for treatment-naïve patients with HCV genotype 3 infection who have compensated cirrhosis.¶
Rating: Class IIa, Level B

[Lynn K]

Well even if you are F3 that is not really cirrhosis. Has your doctor diagnosed you with cirrhosis? A Fibroscan is less accurate in the mid ranges. The liver biopsy remains as the gold standard for cirrhosis diagnosis although is is still somewhat imperfect due to possible damping error.

I wouldn't use the word powerful rather perhaps more effective at combating the virus. But your doctors will need to make the call on the best treatment for you based on your current medical condition. They are the experts.

[Jorah]

LOL  They can't make up their mind, I get a different fellow intern each time.. I fall under the head doctor of the liver clinic, but all these big doctors have interns that see the patients that then report back to the big Doctor.  Last month I told them I want to see my main doctor and he finally said that my fibrotests are 0.54 consistent with F2.
Fibroscans were less consistent in June 2015 was 12.4 F3-F4 advanced fibrosis. Eight months later they were down to 8.4 and then 10.3. My main Doctor thinks that I'm borderline cirrhosis.
They want me on Epclusa not Daklinza, I hope the decision they make is the right one. I don't always trust doctors, I've seen some in the past get influenced by the pharmaceutical companies. This is why I was asking around.
But the idea that you need less Epclusa than daklinza for cirrhosis treatment sounds good. (even if I'm not cirrhotic) 

[Lynn K]

The big consideration to me would be avoiding ribavirin if possible. That medicine can be difficult for many patients. Some people experience a serious rash that has caused some to have to discontinue treatment while others like myself have a reduction in red blood cell counts resulting in anemia which basically meant I got winded on climbing short flights of stairs and generally felt tired and run down on treatment.

Best of luck

[Jorah]

Yes...I'm scared of Riba    the person who's taking care of my case didn't think that they were going to put me on Riba. None of the Doctors I saw said that they would include Riba. Hell, I'm scared of epclusa too reading the stories here... Now they may phase out Riba for voxilaprevir (GS-9857) they had excellent cure rates for people with cirrhosis.
I'm looking at you Sig and you sure went thru hell with all those meds, they tried to put me peg and the other stuff I chose to wait. (but circumstances are not the same for everyone of course)

[Lynn K]

Well riba wasn't fun but one can do whatever you put you mind to do. Back 1995 there were no easy meds that was all there was so I did what I had to do. Didn't work but I had to try.

Most people have a very easy time with treatment only a small minority report having a difficult time with treatment.

My best advice is don't borrow worry about a tomorrow that may never come.

Best of luck to you

[Jorah]

Thanks Lynn   

[elias]

Two points to consider:

1) If you look at the Phase III clinical trials for Epclusa, GT3 failures~5% occurred almost exclusively among  those with cirrhosis. Cirrhosis being defined by level on Fibroscan or Fibrosure.

So with GT 3 non-cirrhotics, the SVR12 rate is ~99% with Epclusa.  I dont think Sovaldi+Daklinza had that high a success rate


2) Sovaldi and Daklinza are by by two different drug companies Gilead and BM Squibb respectively.  The cost of medication combination from two different manufacturers is more than twice as high as a drug combo by one company. Furthermore, Gilead did lower its wholesale acquisition cost for Epclusa significantly below that of its Harvoni combo.  I forgot exact figures. But your insurance co will in the long run be "happier" with Epclusa, even if they refuse you at first. It's to their advantage

[KimInTheForest]

Hi Jorah! Good to see you back here. It's been a while.

I too was Geno 3a, as you probably recall. And I went for the harvoni/ribavirin trial - which worked and was the only way I could get DAAs here in BC at that time (May 2015). But it really took a toll on me, which is still playing out. It was the best option for me at the time. But if I had known Epclusa was coming... well, let's just say I would not hesitate to take Epclusa if I still had HCV. I would also choose Epclusa over Sovaldi/Daklinza because Epclusa is even newer. And it seems with each refinement to the DAAs, the picture gets better. Less sides, higher success rates. etc.

good luck!
kim

[Jorah]

1) If you look at the Phase III clinical trials for Epclusa, GT3 failures~5% occurred almost exclusively among  those with cirrhosis. Cirrhosis being defined by level on Fibroscan or Fibrosure.

So with GT 3 non-cirrhotics, the SVR12 rate is ~99% with Epclusa.  I dont think Sovaldi+Daklinza had that high a success rate

Thanks Elias I looked around and can't find the 99% you mention, I called Gilead (the number at the epclusa website)and the people I spoke to said 95%... that's for those with both cirrhosis and naive..she didn't have the numbers for naive only. My understanding is that with Daklinza/Sofo the cure rate is 97 %. So this is why I wonder why the DR would put me on epclusa rather than daklinza/sofo.
Thanks

[Jorah]

Hey !!   

I pass by occasionally to look at the news, I think we talked since you were cured. Yes I'm also 3a. I'm sorry to hear you're still having trouble..is this because of the ribavirin ? I remember you didn't feel well towards the end. 
I always value you thoughts and information on this issue .
Yes Epclusa is newer and Gilead is on the forefront of these meds, but you know..I saw the 2% spread of daklinza over epclusa..so I started thinking maybe daklinza is better..
I maybe starting meds within a couple of weeks, so I want to make the best decision.

Regards   ..later

Hi Jorah! Good to see you back here. It's been a while.

I too was Geno 3a, as you probably recall. And I went for the harvoni/ribavirin trial - which worked and was the only way I could get DAAs here in BC at that time (May 2015). But it really took a toll on me, which is still playing out. It was the best option for me at the time. But if I had known Epclusa was coming... well, let's just say I would not hesitate to take Epclusa if I still had HCV. I would also choose Epclusa over Sovaldi/Daklinza because Epclusa is even newer. And it seems with each refinement to the DAAs, the picture gets better. Less sides, higher success rates. etc.

good luck!
kim

[elias]

Thanks Elias I looked around and can't find the 99% you mention, I called Gilead (the number at the epclusa website)and the people I spoke to said 95%... that's for those with both cirrhosis and naive..she didn't have the numbers for naive only

Hi again Jorah:

I will tell you how I came to that 99% success rate figure for GT 3 non-cirrhotics with Epclusa

Heres the medical journal write-up for GT 2 and GT3's on Sovaldi/Velpatasvir:

http://www.nejm.org/doi/full/10.1056/NEJMoa1512612?af=R&rss=currentIssue

The: ASTRAL-3 Trial described there is the one you're interested in. It's the large Phase III study of GT3 and Epclusa It's described in much detail in that NEJM article

From that article:

Among the 277 patients who received sofosbuvir–velpatasvir, 11 (4%) had virologic failure after the end of treatment, and 2 patients were lost to follow-up. Characteristics of the 11 patients in the sofosbuvir–velpatasvir group who had a relapse are provided in Table S4 in the Supplementary Appendix.

These 275 patients include  cirrhotic, non-cirrhotic, tx naive and tx experienced. You will notice only 11 of all of these had virological failure.

Now look at who those 11  failures were by going to Table 4 in the Supplementary Appendix.  Which you can find here:

www.natap.org/2015/AASLD/nejmoa1512612_appendix.pdf

Scroll down all the way to Table 4 in that Supplementary Appendix.

You will see that out of the 11 failures, one had reinfected himself later with another GT. SEVEN others had cirrhosis  In other words 70% of the treatment failures not due to reinfection had liver cirrhosis Which is way larger proportionately than in that Phase III treatment group of 275.  Of the three remaining virologic failures who were not cirrhotic, two were tx experienced.


 So only one non-cirrhotic who was tx naive among this large group of 275 GT3 ers had experienced virologic failure.

The difficulty with GT3 and clearing HCV with Epclusa is almost entirely attributable to cirrhosis status.

I can't give you the breakdown with Sofosbuvir/Daklatasvir for GT3. It's not as high as this. and as I pointed out, you'd need two costly medications from two different drug companies. Each of those being way overpriced. Last I  looked Sovaldi itself is (oddly) priced higher it terms of wholesale acquisition cost than is Epclusa.

============
PS:

I had faced a somewhat similar dilemma back in September, when insurance at first denied Epclusa as it wasnt on their formulary. Daklinza however was. But Sovaldi/Dakilnza was not  FDA approved for GT2. Insurance wanted me to go with Sovaldi/Riba Since there's reason to think Daklinza may be pan-genotypic, I was looking into getting the Sof/Dak combo via generics abroad. I realized however it would be in the insurance company's selfish interests to allow "Exception to Formulary" for me and that I could make a  good argument for this. As well as medical argument for avoiding the Riba.  So I did my homework on it. In retrospect, I'm glad I held out for the Epclusa.

[Jorah]

Your numbers make sense Elias, very good investigative skills    My Docs say that I may have beginning of cirrhosis, but hopefully it will still work. (but the're not sure, they say for sure advanced fibrosis, they don't do the the needle biopsy anymore) I'm sure if they thought I had cirrhosis they would've added Riba. (although they now have voxilaprevir)

The daklinza/S for non cirrhotic genotype 3 seems to be 96% (https://www.ncbi.nlm.nih.gov/pubmed/25614962)

You may of heard that Abbvie came out with a pangenic combo that works in 8 weeks. Its 95% for G3 and 97 % for G2.   https://news.abbvie.com/news/eight-weeks-treatment-with-abbvies-investigational-pan-genotypic-regimen-glecaprevirpibrentasvir-gp-achieved-high-svr-rates-across-all-major-genotypes-chronic-hepatitis-c.htm

Good that you were able to get the Epclusa over the Sov/Riba, 24 weeks could be a nightmare with the riba. The wanted first to give me interferon and afterwards the 24 week combo but I didn't do it .
Didn't know daklinza can be pangenic, I know Kim did the harvoni/Riba for G3 and it worked. The small study of 22 (G3) all did well with the harvoni. I know Gilead did a larger study of harvoni for G3, but they wouldn't tell me the results. (Harvoni is approved for G1)

So you're also cured now, I wish you the best and thank you so much for helping.
Later

Hi again Jorah:

I will tell you how I came to that 99% success rate figure for GT 3 non-cirrhotics with Epclusa

Heres the medical journal write-up for GT 2 and GT3's on Sovaldi/Velpatasvir:


The: ASTRAL-3 Trial described there is the one you're interested in. It's the large Phase III study of GT3 and Epclusa It's described in much detail in that NEJM article

From that article:

These 275 patients include  cirrhotic, non-cirrhotic, tx naive and tx experienced. You will notice only 11 of all of these had virological failure.

Now look at who those 11  failures were by going to Table 4 in the Supplementary Appendix.  Which you can find here:

www.natap.org/2015/AASLD/nejmoa1512612_appendix.pdf

Scroll down all the way to Table 4 in that Supplementary Appendix.

You will see that out of the 11 failures, one had reinfected himself later with another GT. SEVEN others had cirrhosis  In other words 70% of the treatment failures not due to reinfection had liver cirrhosis Which is way larger proportionately than in that Phase III treatment group of 275.  Of the three remaining virologic failures who were not cirrhotic, two were tx experienced.


 So only one non-cirrhotic who was tx naive among this large group of 275 GT3 ers had experienced virologic failure.

The difficulty with GT3 and clearing HCV with Epclusa is almost entirely attributable to cirrhosis status.

I can't give you the breakdown with Sofosbuvir/Daklatasvir for GT3. It's not as high as this. and as I pointed out, you'd need two costly medications from two different drug companies. Each of those being way overpriced. Last I  looked Sovaldi itself is (oddly) priced higher it terms of wholesale acquisition cost than is Epclusa.

============
PS:

I had faced a somewhat similar dilemma back in September, when insurance at first denied Epclusa as it wasnt on their formulary. Daklinza however was. But Sovaldi/Dakilnza was not  FDA approved for GT2. Insurance wanted me to go with Sovaldi/Riba Since there's reason to think Daklinza may be pan-genotypic, I was looking into getting the Sof/Dak combo via generics abroad. I realized however it would be in the insurance company's selfish interests to allow "Exception to Formulary" for me and that I could make a  good argument for this. As well as medical argument for avoiding the Riba.  So I did my homework on it. In retrospect, I'm glad I held out for the Epclusa.

[elias]

Hi again Jorah:

Fibrosure of 0.54 is hardly cirrhosis. I think cutoff for that is 0.75. I'm 0.66 which is F3.

I read Fibroscans can be off if you ate within 8 hours of test. It'll read higher. Youre supposed to not eat before Fibrosure blood test as well, but they took the test on me without telling me.

No matter how you slice it, with Epclusa they add Riba only in cases of de-compensated cirrhosis anyhow..

Yes. There are even better medications coming down the pike. But with Sof/Vel/Vox, (which is really Epclusa+Voxilaprevir) they recommend "saving" that in case you fail a DAA and need re-treatment.

Actually when they compared 8 weeks of the Sof/Vel/Vox with 12 weeks of Sof/Vel (=Epclusa), Epclusa had a higher success rate than the even newer Sof/Vel/Vox. Possibly, 12 weeks of Sof/Vel/Vox might beat Epclusa. But insurance companies being what they are, they may decide to approve you for only 8 weeks. They wont be able to  do that with Epclusa, because AFAIK, there's no Epclusa regimen for 8 weeks only.

Glec/Pib by Abbvie  is promising as well. But neither of these is yet approved by FDA. Wont be until the summer. It's good to know they're around, in case of a rare Epclusa failure. But I wouldn't hold out on Epclusa for those. Not a good idea to wait too long with F2 or F3

Heres a podcast of CME Internet Symposium: Based on: AASLD 2016 Expert Review

http://hosted.medipix.com/aasld2016/

Might help you sort it out, in terms of the new meds being good for re-treatment options etc... Its by leading specialists in the field..

BTW: I'm not cured yet. I took only that VL test 4 weeks after finishing Epclusa.Was undetected then. So I'm SVR4 I guess. But not yet SVR 12. Have to wait for April for that

[Jorah]

Hello Elias , they never told me either that I shouldn't eat for the tests. Grrrrr  Now I know and when they take blood the next time I'll make sure not to eat within 2 hours of the test. I don't remember if I ate within the 2 hours last time I went.
Nice podcast thanks.... I know of one of the Doctors as I get emails from inpractice  hepatology.

Yes, I got mixed up with your SVR time, I thought first April then for some reason I thought differently, but I wish you the best and lets cross fingers.

Thanks for all the information...