Relapsed after Harvoni 8 Weeks, now Epclusa?

[Lukey]

I was told about a new med that's supposed to pick up where Harvoni left off with Harvoni 8 week relapsers.

Is that right? Maybe I should see my gastro people after all. I had canceled the appt with them for Sept.

http://www.epclusainfo.com/

[Lynn K]

Hi Lukey

Have you had resistance NS3 (Q80K polymorphism) & NS5A testing done?

Sofosbuvir-Velpatasvir (Epclusa) is an oral fixed-dose combination of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor and velapatasvir, an NS5A replication complex inhibitor.

Ledipasvir is a potent inhibitor of HCV NS5A, a viral phosphoprotein that plays an important role in viral replication, assembly, and secretion. Sofosbuvir is a nucleotide analog inhibitor of hepatitis C virus NS5B polymerase—the key enzyme mediating HCV RNA replication.

So from what I am seeing is the Harvoni and Epclusa both have the same mechanism of action both being NS5A and NS5B inhibitors.

Here is a link to the current AASLD treatment guidelines for prior treatment failures:
http://www.hcvguidelines.org/full-report/retreatment-persons-whom-prior-therapy-has-failed

This was updated 6 July  2016 in some parts

For those without cirrhosis some excerpts from this document:

Recommended for Genotype 1 HCV NS5A Inhibitor Treatment-Experienced Patients
Recommended regimens are listed in groups by level of evidence, then alphabetically.
 

    Deferral of treatment is recommended, pending availability of data for patients with HCV genotype 1, regardless of subtype, in whom previous treatment with any HCV nonstructural protein 5A (NS5A) inhibitors has failed, who do not have cirrhosis, and do not have reasons for urgent retreatment.
Rating: Class IIb, Level C
 
Testing for resistance-associated variants that confer decreased susceptibility to NS3 protease inhibitors and to NS5A inhibitors is recommended for patients with HCV genotype 1, regardless of subtype, in whom previous treatment with any HCV nonstructural protein 5A (NS5A) inhibitors has failed, and who have compensated cirrhosis,‡ or have reasons for urgent retreatment. The specific drugs used in the retreatment regimen should be tailored to the results of this testing as described below.
Rating: Class IIb, Level C
 
When using nucleotide-based (eg, sofosbuvir) dual DAA therapy a treatment duration of 24 weeks is recommended, and weight-based ribavirin, unless contraindicated, should be added.
Rating: Class IIb, Level C
 
If available, nucleotide-based (eg, sofosbuvir) triple or quadruple DAA regimens may be considered. In these settings treatment duration ranges from 12 weeks to 24 weeks (see text), and weight-based ribavirin, unless contraindicated, are recommended.
Rating: Class IIb, Level C

Ledipasvir/sofosbuvir failures

Data on the retreatment of patients for whom prior treatment with ledipasvir/sofosbuvir has failed are very limited. In a pilot study, 41 patients with and without cirrhosis who did not achieve an SVR with 8 weeks or 12 weeks of ledipasvir/sofosbuvir were retreated with 24 weeks of ledipasvir/sofosbuvir. (Lawitz, 2015b) SVR12 rates varied according to the presence or absence of NS5A inhibitor RAVs. Among 11 patients for whom NS5A inhibitor RAVs were not detected, SVR occurred in 11 of 11 (100%); in contrast, among 30 patients for whom NS5A inhibitor RAVs were detected, SVR occurred in 18 of 30 (60%). Importantly, NS5B inhibitor RAVs (eg, S282T) known to confer decreased activity of sofosbuvir were observed in 3 of 12 (25%) patients for whom the retreatment regimen was not successful. (Lawitz, 2015b) Similarly, in the OPTIMIST-2 study in which patients with cirrhosis were treated with simeprevir and sofosbuvir, the presence of NS3 RAVs, namely the Q80K polymorphism, led to a decreased SVR rate in patients with HCV genotype 1a infection. SVR occurred in 25 of 34 (74%) patients with HCV genotype 1a and the Q80K RAV and in 35 of 38 (92%) patients with HCV genotype 1a without the Q80K RAV. (Lawitz, 2015) Based on these data, retreatment for patients for whom an NS5A inhibitor-containing regimen has failed should be considered in the context of retreatment urgency and the presence or absence of RAVs to inhibitors of NS3 and NS5A. Further, based on limited data, ribavirin is recommended as part of all retreatment regimens for patients in whom prior treatment with NS5A inhibitors has failed. Although no data exist, consideration may also be given to the addition of PEG-IFN to the retreatment regimen in patients who are eligible for this agent; PEG-IFN will have antiviral activity regardless of the RAVs present.

But your doctor may have other information I would at least check in and see what their thoughts are for your individual situation

Best of luck to you
Lynn

[Lynn K]

From the prescribing information for Epclusa

"The efficacy of EPCLUSA has not been established in patients who have previously failed treatment with other regimens that include an NS5A inhibitor."

http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.pdf

[Coach Mike]

Sorry L,
You can get some really good advice at FixHepC.com. Join and ask your question there as well. I'm sure Dr. Freeman will offer some excellent advice.
8 weeks is what my GI prescribed to give me a better chance for insurance approval.
Dr. Freeman insists on 12 weeks minimum. I don't know if it would have made any difference in your case, but you were very close to the 6 million v/l threshold.
You have options that don't involve waiting.
Good Luck!
cm

[Lukey]

Hello and thanks.

After relapsing, my VL went from 782k to 420k, then to 380k and I was thinking I was going to control it. Then I went on LDN (low dose naltrexone) last Dec 2015 and I didn't test again until 2 weeks ago but that was 5 weeks after I quit LDN, and it was up to 2.7 million, but my AST and ALT improved to about 20 points each over the max at 67 & 87. I'm back on LDN again as of 1 week ago. It's done some nice things for me but I had stopped it to try some other therapy which didn't seem like it was going to be good. I think my HCV flared bc I had quit LDN but if I'd tested while on LDN I think it would have been impressive, tho I don't know this for sure, but I felt better on LDN. An immune modulator is what it is. Things like HCV can bog the immune system down, and LDN is like throwing coal on a fire in a steam locomotive firebox. I used to have severe allergy to an inhalant mold and would get very agitated and would destroy things if I didn't take antihistamine. I even spent 10 days in state MH hospital bc of it, but was exposed to it again after being on LDN a few months and I just brushed it off like a mosquito bite. That's the good LDN does to the immune system. It was a piece of cake. I've heard of people becoming UND for HCV on LDN. I've also heard of people getting AST and ALT in the normal range and staying there on LDN. It's really a wonderful and a low cost med that's given lots of people with all kinds of things their lives back again. People with MS love it, and other auto immune disorders. People with allergies love it. Most people who take it seem to like it a lot. LDN may not get rid of Hep but it will make Hep a non issue for most people. I really don't even know if I'd want to risk another Hep C med, or the letdown of relapsing after UND status again.    I can be well w/o the UND status. It's what I call having HCV under control.

[Lynn K]

Well just keep an eye on your fibrosis if you don't progress and you can deal with living with being infected with hep c not treating is an option. But if you do start to have an increase in liver damage which is not indicated by ALT AST test results but rather be biopsy, fibroscan or fibrosure testing you should definitely consider treating.

Best of luck to you whatever you decide
Lynn

[Lukey]

Thanks Lynn

[FutureThinker]

Hi Lukey, someone on this forum is/was in a clinical trial recently taking the Epclusa + another drug (I think), that the member said was touted to possibly be a good option for Harvoni relapsers.  Scroll thru the "Post treatment" topics and you'll probably find it. So if the Epclusa isn't a good match for your RAVs, perhaps this future drug will be.  FT

[FutureThinker]

Lukey, I found it, the info on the clinical trial was posted by HHburme and the trial was using Epclusa + Voxilaprevir.  You can read about it at clinicaltrials.gov, Trial # GS-US-367-1171, the POLARIS 1 study. I don't know when it's expected to be approved by the FDA, but check it out.  FT

[Coach Mike]

Some good info on relapse:

http://fixhepc.com/forum/retreatment-corner/1176-how-long-to-wait-before-retreatment.html#19522

cm

[Lukey]

Thanks again.

[FutureThinker]

Coach Mike ----- CONGRATS ON YOUR SVR 24!!!!!!!!!  I was thinking you were close to that point just recently.  What a sigh of relief that this is over for you, after all you had to go thru........ so glad to hear it. I am still waiting for SVR 12, in the next 3.5 weeks and hope to have good news to report, too.  How are you feeling at this point?  FT

[Coach Mike]

Thanks FT!
You've got this hammered, I just know...
I don't have a "normal" to compare against, because I've had this crap all my adult life, BUT, I feel as good as a soon-to-be 63 year old ought to feel, I suppose. I am fortunate to have not killed myself drinking a bit too much over the years, not knowing my liver had other battles to fight...but that is no longer an issue.
Drinking excessively or that "other" other battle.
I feel fortunate and relieved. It was a nightmare that turned into a pitched battle. Knowledge is a great weapon. So are caring people to advise and provide support. My long-time PCP, as well as Dr. James Freeman, Lucinda and HepMag, Greg Jefferys and the wonderful people here and at FixHepC deserve the everlasting thanks of this former HCV sufferer.
They have it-in spades...
Thanks again, to you and all.
cm

[andrew j]

Hi Lukey,

... I'm just wondering how you are - and where you're at with this relapse
stuff?


Best regards,
Andrew J.