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1930700 tn?1327068504

Sovaldi and Olysio My Update

I was approved for both S&O...however my test came back that I was resistant to Olysio becaue the Q80K was detected.  The Q8OK polymorphism has been found to have a significant impact on SVR in patients with HCV genotype 1A (me).  I don't know why they didn't mention Solvaldi...but will ask on a follow-up with Dr.  He said, since I was resistant (80% chance) I should wait for a better treatment or trial and mentioned one that will come out in May - called Jenssen.  (better over 90% cure..rate)

He did a Fibrosure which the good new was that I was not a candidate for some other trial called Abbvie.....(sorry don't have exact names.  He said, you don't have the C word which I took as good news.  My 2011 biopsy said was 2/3...

Now:  The Fibrosure Score. 0.16 Fibrosis Stage F0 - No Fibrosis, Necroinflammat Activity Grade: A-2 moderate activity..something called Apolipoprotein - A-1 at 211 which is High... (don't know what that means).  

I am treatment naive...(been waiting for the orals)...so was excited that finally I got the orals and APPROVED by insurance only to find I am resistant to at least Olysio. :-(

Anyone familiar Jassen trial?  Do my numbers above still look good?

As always, thanks for your continuous help...
Millie
32 Responses
Avatar universal
Q80K polymorphism: QUEST-1 and QUEST-2 studies
In  the simeprevir QUEST-1 and QUEST-2 studies, researchers reported in QUEST-1 patients with HCV genotype1a had almost 20% less SVR than HCV genotype 1b. Noted, at baseline the mutation Q80K was found in approximately 1/3 of genotype 1a patients. On the contrary, in QUEST-2 this mutation was infrequent and did not impact significantly the SVR rate.

http://hepatitiscnewdrugresearch.com/olysiosimeprevir-resistant-variant-q80k.html
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Before making a final decision I would ask my doctor about the results from the QUEST-2 trial which I would figure had a much larger enrollment of patients... Wishing you the Best
1815939 tn?1377995399
"I was approved for both S&O...however my test came back that I was resistant to Olysio becaue the Q80K was detected.  The Q8OK polymorphism has been found to have a significant impact on SVR in patients with HCV genotype 1A (me). "
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If you have the Q80K polymorphism and treat with Simeprevir (Olysio), Interferon and Ribavirin, the SVR rates are considerably lower than if you did not have the Q80K polymorphism.

"Olysio (simeprevir), the first "second wave direct-acting antiviral" to treat HCV was recently FDA approved for genotype 1 in combination with peginterferon alfa and ribavirin in adults with compensated liver disease,"

http://hepatitiscnewdrugresearch.com/olysiosimeprevir-resistant-variant-q80k.html


However, if you treat with Sofosbuvir (Sovaldi) and Simeprevir (Olysio) combined, the Sofosbuvir mitigates the effect of the Q80K polymorphism and the SVR rates are high.

"**A study of an all-oral combination of simeprevir with Gilead's sofosbuvir has shown that the regimen mitigates the effect Q80K has on simeprevir, Gaston Picchio, hepatitis disease area leader at J&J's Janssen unit, said during the meeting."

Same link as above.


Ask your doctor about treating off label with Sovaldi and Olysio because the SVR rates are very high. The Sovaldi mitigates the Q80K polymorphism's effect on Olysio. Your chance of SVR (cure) with this all oral combo is excellent, even if you do have the Q80K polymorphims.


"Simeprevir and Sofosbuvir Cure Hep C Genotype 1 at High Rates"

"A 12-week regimen of Janssen’s simeprevir and Gilead Sciences’ sofosbuvir boasts high cure rates among those with genotype 1 of the virus, the most common in the United States and the most difficult to treat, aidsmap reports. .....

Each of the two drugs is weeks from a likely approval from the U.S. Food and Drug Administration. And while the FDA will not be approving simeprevir and sofosbuvir for use in combination at this time, the findings of the COSMOS study may influence clinicians’ decisions to prescribe them together off-label, in particular for patients with more urgent needs for treatment.

The trial had two groups of participants, all of whom had genotype 1 of hep C. The first included 80 people who were null-responders to previous interferon-based treatment who had absent-to-moderate fibrosis. The second group included 87 either treatment-naive or prior null-responder participants who had advanced fibrosis or compensated cirrhosis. All the participants were randomly assigned to receive either once-a-day treatment of the protease inhibitor simeprevir and the nucleotide polymerase inhibitor sofosbuvir or the same regimen plus ribavirin twice a day. The group was further randomized to receive treatment for either 12 or 24 weeks.

Among those in the first group who were treated for 12 weeks, 93 percent of the participants taking dual therapy achieved a sustained virologic response 12 weeks after completing treatment (SVR12, considered a cure), compared with 96 percent taking the triple regimen. .....

In group 2, all of the seven treatment-naive and the seven null-responder participants on the dual regimen who also had adequate follow-up reached an SVR four weeks after completing treatment (group 2 started treatment after group 1, so there is less follow-up data). Among those on the triple regimen, 100 percent of treatment-naive participants and 93 percent of the null responders achieved an SVR4."

http://www.hepmag.com/articles/sofosbuvir_simeprevir_2501_24726.shtml


"Interim results from Cohort 2 of the COSMOS study evaluating Simeprevir and Sofosbuvir in HCV patients with METAVIR scores F3-F"

In Hepatitis C patients with advanced liver fibrosis or cirrhosis (METAVIR F3 or F4) 12 weeks all oral treatment with simeprevir and sofosbuvir with or without ribavirin led to SVR4 rates of 96% and 100%, respectively.....

Stockholm, Sweden - Medivir AB (OMX: MVIR) today announced interim results from the second Cohort in the ongoing COSMOS study evaluating a once daily combination of simeprevir and sofosbuvir in hard to cure hepatitis C (HCV) patients.

SVR4 results from the 12 week arms of Cohort 2, including treatment naïve or previous null responder HCV patients all with METAVIR score F3-F4 were reported. Treatment for 12 weeks with simeprevir and sofosbuvir, with or without ribavirin, led to SVR4 rates of 96% and 100%, respectively.

Interim results from Cohort 1 of the COSMOS study, which include only prior null responder HCV patients (METAVIR F0-F2) have been reported earlier and demonstrated SVR8 rates of 96% and 93% after 12 weeks treatment simeprevir and sofosbuvir with and without ribavirin, respectively......

COSMOS is a randomized, open label, phase IIa clinical trial evaluating a once-daily combination of the HCV protease inhibitor simeprevir and the nucleotide sofosbuvir with and without ribavirin (RBV) for 12 and 24 weeks. Cohort 1 (n=80) evaluates prior null responder genotype 1 hepatitis C (HCV) patients with METAVIR scores F0-F2 and Cohort 2 (n=87) evaluates prior null responder and treatment-naïve genotype 1 hepatitis C patients with METAVIR scores F3-F4. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver. Liver fibrosis is scored on a four-point scale. At the time of the interim analysis, SVR4 results were available for all patients (n=41) in the 12 week arms of Cohort 2. In this Cohort, 78.2% of patients had GT1a subtype with 40% of those having a Q80K baseline polymorphism, 79.3% had IL28B CT or TT genotype, 47.1% had Metavir score F4 (cirrhosis) and 54.0% were prior null responders.

In the previously reported Cohort 1, 77.5% of the patients had GT1a subtype with 50% of those having a Q80K baseline polymorphism, 93.7%, had IL28B CT or TT genotype and 58.8% had METAVIR score F2."

http://www.natap.org/2013/HCV/082913_01.htm
Avatar universal
Olysio (Simiprevir), by Jassen, is an oral protease inhibitor and has a low to medium barrier to resistance.  Sovaldi (sofosbuvir), by Gilead, is a nucleotide analog NS5B polymerase inhibitor and has a high barrier to resistance.

It looks like your doc wants you to wait for a companion drug for Sovaldi that also has a high barrier to resistance, which is a good idea IMO.  What's producing excellent results is Sovaldi is coupled with an NS5A inhibitor, which also has a high barrier to resistance.

There are several NS5A inhibitors on the market.  As I mentioned, Ledipasvir is Gilead's NS5A inhibitor.  Bristol Myers' NS5A inhibitor is known as Daclatasvir.  (When Bristol Myers and Gilead fell out 2 years ago, people made big stink because at that time, it was the only combination of drugs (sofosbuvir & daclatasvir) with a high cure rate and a high barrier to resistance.)  In October 2013, Jassen "acquired" (purchased?) it's own NS5A inhibitor, GSK2336805, for folks with the Q80K and resistance to Olysio.  

Since NS5A inhibitors have a high barrier to resistance, Jassen has wisely acquired their own.  The "Jassen" trial they're talking about must be comprised of Sovaldi coupled with GSK2336805 (or whatever name they eventually give it) NS5A inhibitor.

Take note that ALL NS5A inhibitors (and the new oral protease inhibitors like Olysio) have to be taken with the KING of HCV drugs - Sovaldi.  If you don't have the dreaded Q80K polymorphism, you can take Sovaldi with Olysio, which a lot of folks are doing.  However, if you have Q80K, then you have to couple Sovaldi with an NS5A inhibitor.  I think all the NS5A inhibitors are comparable.

Here's a link about Jassen's acquisition of its new NS5A inhibitor.  
http://www.investor.jnj.com/releasedetail.cfm?ReleaseID=795554

Verify that the Jassen trial you're considering will consist of Sovaldi and GSK2336805 or another NS5A inhibitor.  If so, find out how close the trial is to opening up and RUN, don't walk, to get in line.

Good luck to you,
HC

P.S. [I too had high resistant polymorphisms (to Invicek) and had to stop triple treatment after 12 weeks.  About a year after stopping, I started a Gilead trial with Sovaldi (sofosbuvir) and Ledipasvir (formerly GS-5885).  I've been cured for 10 months after taking those 2 drugs for 12 weeks.]
Avatar universal
P.S. As far as your numbers, you should talk to your doctor about those.  I can't keep track of all those.  If your biopsy has been done and you're eligible for the trial (and it's the one you want), I say go for it.

Again, good luck!

HC
1930700 tn?1327068504
Thank you...hepcat, wow...so happy you been cure...every minute cure is precious.  

pooh and can-do man...very thorough advice.  I am going to print it and have it when I go see my dr.  He said to come back in May...for a better trial or I guess one that he thinks its better than the combo O&S.  I am going to question him about the combo -  and the study you mention that had a better cure rate....so given that I have the dreaded Q80K...I have to wait for something that works with it...or against as it may be.

Oh, boy...so much stuff...

I thank you all..as I said I will print information/advice you sent me and study it....

You are all the best EVER...THANK YOU!
Avatar universal
Pooh said, "Ask your doctor about treating off label with Sovaldi and Olysio because the SVR rates are very high. The Sovaldi mitigates the Q80K polymorphism's effect on Olysio. Your chance of SVR (cure) with this all oral combo is excellent, even if you do have the Q80K polymorphims."

She can't take Olysio because it's resistant to Q80K polymorphisms, which she has... she needs to take Sovaldi with an NS5A inhibitor, which also has a high barrier to resistance.  Her doc advises against taking Olysio with Sovaldi (and I agree 100%), so why push for it?  She should opt for the TX that's NOT resistant, which is Sovaldi + NS5A inhibitor.

Millihepc, find out if the new trial from Jassen has Sovaldi and Jassen's NS5A inhibitor (or another NS5A inhibitor).  Don't take something to which you know you have resistance.  You'll be wasting your time and money.

Good luck,
HC

milliehepc said, "...however my test came back that I was resistant to Olysio becaue the Q80K was detected.  The Q8OK polymorphism has been found to have a significant impact on SVR in patients with HCV genotype 1A (me).  I don't know why they didn't mention Solvaldi...but will ask on a follow-up with Dr.  He said, since I was resistant (80% chance) I should wait for a better treatment or trial and mentioned one that will come out in May - called Jenssen.  (better over 90% cure..rate)"


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