Q80K virus morph?

[mamarocat]

I am told my insurance company wants the Q80k drawn prior to authorization for olysis, because the protease inhibitors target a specific part of the virus which can mutate so as to avoid the drug.  The olysis and solvaldi combo  is ordered to be given off label. Having been on treatment twice, (interferon and RIBA, then changed interferon to Infergen; then triple therapy with incevik, RIBA and interferon)and broken through each time I am hoping to get the results needed and the rotten virus has not morphed! I am so tired of waiting and getting my hopes up, I have developed slight varicies and cirrhosis.  Has any geno 1A been treated after having the virus mutate and been successful?

[mamarocat]

Good luck!

[daroga]

But yesterday I found a lab in uk that accepts specimens from abroad! Now I just have to find a doctor that will let me do it...

[mamarocat]

So sorry to hear that.  Hope,things will work out well for you.

[daroga]

I just received an answer from LabCorp that they do not accept specimens from my country at this time.

[mamarocat]

Quest labs was the only lab in my area.   They took the blood but the test was done  in a lab in California.  I do hope you are able to get some answers
Good luck!.

[daroga]

Thank you. I checked the Quest web page but this test was not listed there as far as I could see. Maybe I will get an answer from LabCorp next week. I am trying to see if it is possible to take the test even though I am not a resident of the US. I would have to pay for it myself if I can find someone that will let me do it.

[mamarocat]

Not sure of actual cost.  Mine was done by quest lab.  ( they sent it to California for processing). I have blue cross.  They said it might cost me between $50 - $100, but I have never received a bill...

[daroga]

What is the price for this Q80K test? Is it only LabCorp that perform them? I contacted them a couple of days ago but have not yet received an answer.

[mamarocat]

My doc says new treatment will be available in October...from all I have read seems to be right....I am hoping we all make the right choices for ourselves....so far I seem to be holding steady.....hoping nothing changes...

[goater]

Hi hepbec,

My understanding is about like yours for early 2015.  It is anyone's guess what impact the health care law will have on the carrier's and their rx formulary when Sol/Led comes to market.  Hopefully, Gilead will make it available at a lower cost than the current off label course.

I'm glad you bumped this post to the top since I missed mamarocat's original older post.

Decided to chance treating again now.  Currently on day 31 of planned 24 week tx of Sol / Oly + Riba (1200).

Cirrhosis-1a.  My GI doc and I discussed testing for poly but decided not to unless insurance required it then we'd do so for appeal.  Tricare approved it within 3 days.

Doc wasn't as excited as I was with these early cirrhotic results and felt I'd remain healthy enough to wait for Sol/Led.  Was Dx'd cirrhosis in 2005 during admission for variceal hemorrhage.  That's at least 9 years, a long time in my head.

Treated 48 weeks with SOC in 2006.  Partial responder.

Treated 48 weeks with SOC/Victrelis in 2011.  Was a late responder, became undetected between weeks 12-24.  Took boatloads of Neupogen and Procrit to avoid dose reduction.  Remained clear at EOT and relapsed at post 3 months.    

I believe up to 48% are poly.  Mararocat, Talisman51, and hdkash I may be there with you but I just don't know.  While poly does reduce the effectiveness of Olysio it doesn't preclude writing for it.  I gave this all some thought and didn't want to waste a potential year for new, albeit better, meds and risk decomp. or development of HCC.  If this tx doesn't pan out I believe there is not a resistance issue with Sovaldi.

Sides, so far, are a cakewalk compared to previous treatments.  Weekly labs and 4 week PCR two days ago.  Bilirubin bumped to 3.9 in week two and 3.2 now.  Hgb was 16 at baseline and remained at 13.9 the past 2 weeks.  

Best wishes for everyone and their decision.  It is a tough call for cirrhotic's.
Marty








    

[hepbec]

I will need to make a decision between the S/O regimen and waiting for Gilead's one pill solution which FDA is scheduled to approve (or not) in October.  Does anyone know how long it will take to come to market if approved in October?  I have seen articles that talk about the new drug "available in 2015"

[Talisman51]

Right there with ya....  1aGT  w/Q80K.
Based on the publicly available 12wk SRV12 numbers from COSMOS, looks like 8 out of 9 q80k+ (includes both naive and non) where SRV12  Crazy small sample size but translates to 88.9% for Q80k+,  If you include the both w/ and w/o Q80k groups you get 20 out of 22 (only one failure in each group) you get 90.9% SRV12.   The ION study (SOF/LDV) for combined naive and non w/ 1aGT 12wks is 311 out of 323 or 96.3%.  Either way 90.9% or 96.3% BOTH great options!  Given the know Simeprevir Q80k resistance I think I can  hold for non PI October regimen.  Difficult personal decision considering lots of factors.
.    

[mamarocat]

Sorry your results were positive, it just stinks!
So you feel 85% success is better than waiting a few months for the next med to be approved?

[hdkash]

So my test was positive too :-(

My Doc and I talked at length and he summarized with "it's an 85+% chance of success! much higher than anything we've tried so far. Worth it to try and lots of options (if your Doc is willing) to fight for approval be it through insurance or patient assistance."
The way he described the potential sides were to compare a decent rain to a tropical storm, been through the storm and yes you will get wet this time but expectations are nowhere near the severity of a storm.
My situation is dynamic as I just found out I am being laid off, so I don't want an interruption of treatment. I will go for it as soon as I either find a job or am dropped by insurance, no insurance might actually help me get financial assistance to cover treatment.
The real take away is that sooner rather than later I (and you) will clear this, if not this round one in the near future, treatment is only getting better.

[mamarocat]

I will be anxious to hear your results, and your octor's recommendations as we have similar experience with prior treatments!

[mamarocat]

Just got the results :(. Results= Mutation detectedQ80k
I am bummed:-(
Am I right in my understanding that with this result it lowers the percentage of SVR to 86% when treated with solvaldi and olysis?

Wondering if anyone else had had this experience?

[mamarocat]

I am classified as stage 2 cirrhosis.  My med team feels strongly that I should have treatment now and are pushing to get insurance approval. They believe the percentage odds for SVR are in my favor...I am still waiting for my lab results to see if there is morphing.  The more I read, the more confused I get...thank you for all the info...I hope that I make the right choice....

[JimmyMose]

Best wishes for getting the best tx in time to achieve SVR and the best future outlook possible.

I am just guessing (non-medical opinion) that your doctor has classified you as stage 2 on a Four-Stage Cirrhosis Classification System.(more info and source link at end) Compensated with varices (no bleeding and lower risk of than decomp) but no ascites.  If your provider has recommended treatment now there should be a good reason.  How strong do you feel about your Hepatology group, including expertise and experience treating liver disease including those with cirrhosis comp or decompensated liver?

Has your doctor explained in detail the reasoning for treating now with SOV/OLY opposed to waiting for newer or other treatments if any?

Although genotype 1a with Q80K mutations had slightly lower numeric response rates in limited test your provider felt that was the best treatment available and your need for it now without testing for Q80K mutations as it wouldn't make a difference.  The insurance company may have a policy requiring testing  for Q80K mutations.  Your provider may have to appeal if denied with thorough details and arguments to try and get approval.  

Have you asked your provider if NS3 Q80K polymorphism is present and the fact you failed prior triple therapy with Telaprevir have any effect on recommendation.  Disclaimer I don't know much if anything about this scenario but more details may be helpful for some others.

This is just an example of one recent insurance company Olysio Plan.   Effective: April 8, 2014  Tuffs Health Plan
http://www.tuftshealthplan.com/providers/pdf/pharmacy_criteria/olysio.pdf
excerpts
Olysio (simeprevir) is a protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. The efficacy of Olysio (simeprevir) has been established in combination with peginterferon alfa and ribavirin in HCV genotype 1 infected patients with compensated liver disease (including cirrhosis). Olysio must not be used as monotherapy. The efficacy of Olysio (simeprevir) in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with HCV genotype 1a with an  NS3 Q80K. polymorphism at baseline compared to those without this polymorphism. Screening of patients with HCV genotype 1a infection for the presence of virus with NS3 Q80K polymorphism at baseline is strongly recommended. Alternative therapy should be considered for patients with this polymorphism. Olysio (simeprevir) should not be used in patients who have failed previous therapy which included a protease inhibitor.

4. What is the specific genotype? Genotype 1a: Go to #5
5. Is the NS3 Q80K polymorphism present? Yes or Unknown: Not
Covered* *Requests for non-covered indications or uses will be considered on a case by case basis.

LIMITATIONS
1. Olysio (simeprevir) will only be approved when used in combination with pegylated interferon and ribavirin.
2. Olysio (simeprevir) will be approved in combination with Sovaldi™ (sofosbuvir) only if the member is treatment naïve, cirrhotic, and is not eligible to receive interferon or the member is a prior non-responder to interferon and ribavirin therapy. The combination will be approved for up to 12 weeks of sofosbuvir and simeprevir with or without ribavirin for interferon ineligible and up to 24 weeks for post-liver transplantation.
__________________________________________________________
Details  Four-Stage Cirrhosis Classification System.
Patients with cirrhosis can be subcategorized as having four stages, with stages 1 and 2 classified under Compensated category and stages 3 and 4 in the Decompensated category. The risk of death increases significantly with each more advanced stage.

http://hepatitisc.uw.edu/pdf/evaluation-staging-monitoring/evaluation-prognosis-cirrhosis/core-concept/all
Some experts have proposed a 4-stage cirrhosis classification system that encompasses the spectrum of compensated and decompensated disease

[mamarocat]

Thank you for all the input.  I have had the bloodwork drawn today. It takes about a week or so for results.   I am still in a quandary as to whether or not to wait for the ledipasvir or hope they accept me for olysis and solvaldi..  My Hepatology group is pushing for treatment now but that was a month ago when we first started trying to get insurance acceptance of treatment..with the way things change so fast... My head is spinning !
It is so very helpful to have this forum to bounce things off of..thank you.

[JimmyMose]

I listed a few VA links in the above medhelp question link

my last comment there was to include this direct link to the latest detailed treatment chart box.
http://www.hepatitis.va.gov/pdf/2014hcv.pdf

But you can also checkout the VA guide links for sofosbuvir and simeprevir in an earlier comment there.  I wonder if the VA is doing an unofficial phase? 4? study and treatment at the same time. They have up to date electronic health info for patient (3 day delay usually) download. Maybe not totally functioning but my guess quick sharing and compiling of specific patient conditions, tests, and treatment, side effects and SVR details., Minus personal information like name & ss number across the entire US VA health system to be analyzed by top health professionals. .

[JimmyMose]

Thank you,  Just wanted to mention these additional excerpts from HCVguidelines.org.....updated 3/21/2014
___________________________________________
Treatment naive GT!
sofosbuvir  plus the HCV protease inhibitor simeprevir (Olysio), with or without ribavirin for 12 weeks.

There is one more paragraph below this one for
"...Thus Q80K testing can be considered but is not strongly recommended."

This regimen should be considered only in those patients who require immediate treatment, because it is anticipated that safer and more effective IFN-free regimens will be available by 2015.
______________________________________________
Treatment Recommended regimen for HCV genotype 1 PEG/RBV (without an HCV protease inhibitor) nonresponder patients:
sofosbuvir  plus the HCV protease inhibitor simeprevir (Olysio), with or without ribavirin for 12 weeks.

"The safety and efficacy of simeprevir have not been studied in HCV-infected patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). The uncertain impact of cholestasis and the occasional association of SMV with elevated transaminases create potential for drug accumulation or impaired hepatic function during SMV use. Clinical trials with SMV have been limited to patients with compensated disease who have CTP class A, total bilirubin of 1.5 x ULN or lower, and transaminases 10 x ULN or lower. For these reasons, simeprevir use should be limited to patients with compensated liver disease. Use of simeprevir is not recommended in patients with moderate to severe hepatic impairment. The combination of PEG/RBV is contraindicated in patients with decompensated cirrhosis (moderate or severe hepatic impairment; CTP class B or C)

decompensated cirrhosis
Patients with decompensated cirrhosis (moderate or severe hepatic impairment; CTP class B or C) should be referred to a medical practitioner with expertise in that condition (ideally in a liver transplant center).
____________________________________________
This statement applies to all treatments
"In many instances, however, it may be advisable to delay treatment for some patients with documented early fibrosis stage (F 0-2), because waiting for future highly effective, pangenotypic, DAA combinations in IFN-free regimens may be prudent. Potential advantages of waiting to begin treatment will be provided in a future update to this guidance".

My Opinions
This is why it's so important to have a very good experience gastroenterologist with knowledge and direct treatment experience including cirrhosis liver disease and hepatology. F3/F4 compensated

Since GT1 nieve  "This regimen should be considered only in those patients who require immediate treatment," that why only medical practitioner with expertise in cirrhosis and liver disease can make that decision.  The doctor through examinations, tests and patient symptoms should be able to to judge how urgent treatment is needed, how often to monitor if waiting, when to treat with what drugs and act immediately to treat if change in cirrhosis progression is detected.    A expert doctor may decide that a specific liver decompensation condition warrants trying Sovaldi Olysio combo.

There is concern about Olysio in moderate or severe hepatic impairment.
Just like there is concern about Sovaldi in severe renal impairment but not as much with Olysio. More time and experience  is needed

My guess what if Ledipasvir gets approved and is safer than Olysio then Gilead decides to sell Ledipasvir a little lower than Olysio. They still make the big bucks on Sovaldi to cover the expensive purchase and corner the market for a little while at least.  

FYI I posted a few comments here about new VA guidelines that mostly agrees with hcv guidelines with a couple differences. see links for complete information.  Like GT2 experience SOV/RBV 16 weeks??  SOV/RBV GT1 close to non recommended except for waiting on transplant or certain post transplant etc.
http://www.medhelp.org/posts/Hepatitis-C/Anyone-getting-Sovaldi-from-VA-yet/show/2149301

[candyce1953]

http://www.prnewswire.com/news-releases/final-data-from-the-phase-2-cosmos-study-of-janssens-once-daily-simeprevir-in-combination-with-sofosbuvir-presented-at-the-international-liver-congress-2014-of-the-european-association-for-the-study-of-the-liver-easl-255020241.html

These are the final results to cosmos phase two cohort two trial, showing the proper combinations for 1a"s

Good luck

[Pamelajean1]

HCVguidelines.org.....updated 3/21/2014

The American Association for the Study of Liver Diseases (AASLD), the Infectious Diseases Society of America (IDSA) and the International Antiviral Society USA jointly issued new guidelines for the treatment of hepatitis C this week. The guidelines recommend how the newly licensed direct-acting antivirals sofosbuvir and simeprevir should be used in the treatment of all hepatitis C virus (HCV) genotypes. The guidelines will be updated regularly as new data and agents become available. New sections on eligibility for treatment, monitoring of treatment and management of acute infection will be added soon.

"It is important to keep in mind that FDA only will approve drugs that have gone through rigorous testing," said IAS-USA panel co-chair Michael Saag from the University of Alabama at Birmingham. "We cannot run a Phase 3 trial on every possible [drug] combination or every possible patient population. The website allows experts in the field to look at the emerging data and craft what we feel the evidence supports, [which] may fall short of what is specifically in an FDA-approved package insert."

"For genotype 1 patients who cannot take interferon, the panel recommends sofosbuvir plus the HCV protease inhibitor simeprevir (Olysio), with or without ribavirin, again for 12 weeks. This off-label regimen has not been through full Phase 3 testing, but performed very well in the Phase 2 COSMOS trial.
An alternative for this group is sofosbuvir plus ribavirin for 24 weeks, though the panel noted that it is not as effective as sofosbuvir plus simeprevir, especially for patients with liver cirrhosis."

"For patients infected with genotype 1a HCV, baseline resistance testing for the Q80K polymorphism may be considered. However, in contrast to using simeprevir to treat a genotype 1a HCV patient with PEG/RBV when the mutation markedly alters the probability of an SVR, the finding of the Q80K polymorphism does not preclude treatment with simeprevir and sofosbuvir, because the SVR rate was high in patients with genotype 1a/Q80K infection (SVR12 rate for cohort 1 was 86% [24 of 28 patients]; SVR4 rate for cohort 2 was 90% [10 of 11 patients]). To date, virologic failure has not been observed in patients in either cohort infected with HCV genotype 1b and with HCV genotype 1a in the absence of the Q80K polymorphism. Thus Q80K testing can be considered but is not strongly recommended."

The American Association for the Study of Liver Diseases and the Infectious Diseases Society released Recommendations for Testing, Managing, and Treating Hepatitis C. Guidelines from these two medical associations carry huge weight, as many medical providers use this expert advice in their own practices. These guidelines are simply written and public, allowing patients access to the latest advice from leading authorities on hepatitis C.

Hope this helps!