Aa
Off Label Treatment
I haven't been here since 2005/06 when I treated the first time. I am a relapser. Looking through the questions and comments on here brought back such memories. At one time I knew all the answers for treatment and all the medical jargon. I'm now so out of it......
Anyway, I'm allergic to interferon. Of course, it's so rare my dr didn't pay attention to me and I did all 48 weeks of tx. Then I was found to have sarcoidosis. I can't take interferon again. So now the semeprevir, saldavi and riboviron tx for 12 weeks. 12 weeks??? I couldn't believe it. I was going in expecting another 48 weeks.
I'm 1a. viral load 6,528,000. hgb 13.1 What is this about a mutation? I am unaware of this. Valorie
Anyway, I'm allergic to interferon. Of course, it's so rare my dr didn't pay attention to me and I did all 48 weeks of tx. Then I was found to have sarcoidosis. I can't take interferon again. So now the semeprevir, saldavi and riboviron tx for 12 weeks. 12 weeks??? I couldn't believe it. I was going in expecting another 48 weeks.
I'm 1a. viral load 6,528,000. hgb 13.1 What is this about a mutation? I am unaware of this. Valorie
According to the articles above, if you are treating with Sofosbuvir and Simeprevir, then you don't really have to worry about the Q80K polymorphism. The Sofosbuvir mitigates the effects of the polymorphism. According to the article, you would treat for 12 weeks. The treatment has a high cure rate.
Best of luck.
Best of luck.
Thanks for the info. Had to read it a few times to get my mind around it. I asked Bridget about the mutation and she didn't seem to know about it. Since it is so prevalent in the US and my dr isn't testing for it I may be destined to do the 24 weeks of tx.
Hey there! Didn't really expect familiar faces to still be around. Nice to see "friends" again. :) Started TX yesterday. We'll see how it goes this time.
Thank you. That is awesome article found it very exciting knowledgable. Thank you again so much.
Valorie
Valorie
Bean!!! My goodness the old faces are coming out of the wood work. :) I am so glad to see all of you. I start TX this Thursday the 27th.
Looking forwarding to see you again and renewing our friendships and making new ones.
Kindest Regards, Valorie
Looking forwarding to see you again and renewing our friendships and making new ones.
Kindest Regards, Valorie
I'm also 1a, F4 and just started tx with Solvadi/Olysio without the ribavirin. The following is a recommendation based on results of the Cosmos trial.
This is an update from 2/13/2014....
The American Association for the Study of Liver Diseases (AASLD), the Infectious Diseases Society of America (IDSA), and the International Antiviral Society-USA (IAS-USA) this week announced the first new hepatitis C treatment guidelines that include next-generation direct-acting antiviral agents recently approved by the FDA. The guidance is available on a new website, HCVguidelines.org, that will enable frequent updates to reflect emerging data.
"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."
This is an update from 2/13/2014....
The American Association for the Study of Liver Diseases (AASLD), the Infectious Diseases Society of America (IDSA), and the International Antiviral Society-USA (IAS-USA) this week announced the first new hepatitis C treatment guidelines that include next-generation direct-acting antiviral agents recently approved by the FDA. The guidance is available on a new website, HCVguidelines.org, that will enable frequent updates to reflect emerging data.
"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."
I know. Can you believe it - 12 weeks with out interferon. It is absolutely unbelievable and about time. I treated with you in 2005 and 6 and failed too. I did clear with Victrelis, but I don't wish either of the PI"s on anyone and am so grateful there is finally a successful treatment without INF. I am not up on this current treatment but you know this is the place to find out.
My very best
bean (Kathy)
My very best
bean (Kathy)
Hi Val. Nice to see you. I'm not really up to date on the new stuff like others are. But, yes, there is more effective non-interferon treatment for geno 1 these days.
I have copied and pasted the info about the Q80K polymorphism in many Genotype 1a patients. I also included the link to the article.
Please note the paragraph towards the bottom of the article, which I have separated out and put first:
"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."
So it appears that if the Sofosbuvir is included in the treatment regimen, then the Q80K polymorphism does not affect SVR. If Sofosbuvir is not included in the treatment regimen then the SVR rate is considerable lower if one has the Q80K polymorphism.
From Hepatitis New Drug Research
OLYSIO™ (simeprevir) - Q80K polymorphism
"Last month, Olysio (simeprevir), the first "second wave direct-acting antiviral" was FDA approved in combination with peginterferon alfa and ribavirin to treat HCV genotype 1, adults, with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin. Although, simeprevir appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, and easier to take, there are some drawbacks. Before starting simeprevir patients with HCV genotype 1a need to be screened for a genetic mutation called Q80K polymorphism. Alternative therapy should be considered for people with the mutation, according to simeprevir prescribing information.
In the QUEST-1 and QUEST-2 studies, researchers reported in QUEST-1 patients with HCV genotype 1a had almost a 20% less SVR than HCV genotype 1b. As 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.
Johnson & Johnson went on to perform an analysis pooling all subjects from the C205, C206, C208, C216, and HPC3007 trials, and found 48 percent of U.S. patients with a HCV genotype 1a had the Q80K polymorphism at baseline, compared to only 19 percent of patients in Europe. The mutation is almost nonexistent in those with a genotype 1b infection.
**Notably, no Q80K-related reductions in efficacy were observed during the pivotal trials of the currently approved NS3/4A protease inhibitors, telaprevir and boceprevir.
Excerpt: OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C, November 2013
Genotype 1a treatment-naïve patients receiving OLYSIO who had the Q80K polymorphism
In the QUEST-1 and QUEST-2 studies, among genotype 1a treatment-naïve patients receiving OLYSIOTM who had the Q80K polymorphism (a naturally occurring variation in the HCV NS3/4A protease enzyme), 58 percent achieved SVR12 versus 84 percent of patients without the Q80K polymorphism. In the placebo arm, 52 percent of patients with the Q80K polymorphism achieved SVR12. In the PROMISE study, among prior-relapser patients with the Q80K polymorphism who received OLYSIOTM, 47 percent achieved SVR12 versus 78 percent of patients without the polymorphism. In the placebo arm, 30 percent of patients with the Q80K polymorphism achieved SVR12.
Table 2 presents SVR12 data by subgroups from the pooled studies in treatment-naïve subjects (C208 and C216) as well as from the trial in subjects who relapsed after prior interferon-based therapy (HPC3007). In all other subgroup analyses presented in Table 2, SVR12 rates were significantly higher in the simeprevir group compared to the Control group.
*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.
As mentioned, given the high frequency of the Q80K polymorphism in the U.S. population and its significant negative impact on rates of SVR12, according to the prescribing information, the FDA is recommending that all Genotype 1a patients be screened for the Q80K polymorphism. Alternative treatment options should be considered for patients found to be infected with this polymorphic variant."
Please note the paragraph towards the bottom of the article, which I have separated out and put first:
"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."
So it appears that if the Sofosbuvir is included in the treatment regimen, then the Q80K polymorphism does not affect SVR. If Sofosbuvir is not included in the treatment regimen then the SVR rate is considerable lower if one has the Q80K polymorphism.
From Hepatitis New Drug Research
OLYSIO™ (simeprevir) - Q80K polymorphism
"Last month, Olysio (simeprevir), the first "second wave direct-acting antiviral" was FDA approved in combination with peginterferon alfa and ribavirin to treat HCV genotype 1, adults, with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin. Although, simeprevir appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, and easier to take, there are some drawbacks. Before starting simeprevir patients with HCV genotype 1a need to be screened for a genetic mutation called Q80K polymorphism. Alternative therapy should be considered for people with the mutation, according to simeprevir prescribing information.
In the QUEST-1 and QUEST-2 studies, researchers reported in QUEST-1 patients with HCV genotype 1a had almost a 20% less SVR than HCV genotype 1b. As 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.
Johnson & Johnson went on to perform an analysis pooling all subjects from the C205, C206, C208, C216, and HPC3007 trials, and found 48 percent of U.S. patients with a HCV genotype 1a had the Q80K polymorphism at baseline, compared to only 19 percent of patients in Europe. The mutation is almost nonexistent in those with a genotype 1b infection.
**Notably, no Q80K-related reductions in efficacy were observed during the pivotal trials of the currently approved NS3/4A protease inhibitors, telaprevir and boceprevir.
Excerpt: OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C, November 2013
Genotype 1a treatment-naïve patients receiving OLYSIO who had the Q80K polymorphism
In the QUEST-1 and QUEST-2 studies, among genotype 1a treatment-naïve patients receiving OLYSIOTM who had the Q80K polymorphism (a naturally occurring variation in the HCV NS3/4A protease enzyme), 58 percent achieved SVR12 versus 84 percent of patients without the Q80K polymorphism. In the placebo arm, 52 percent of patients with the Q80K polymorphism achieved SVR12. In the PROMISE study, among prior-relapser patients with the Q80K polymorphism who received OLYSIOTM, 47 percent achieved SVR12 versus 78 percent of patients without the polymorphism. In the placebo arm, 30 percent of patients with the Q80K polymorphism achieved SVR12.
Table 2 presents SVR12 data by subgroups from the pooled studies in treatment-naïve subjects (C208 and C216) as well as from the trial in subjects who relapsed after prior interferon-based therapy (HPC3007). In all other subgroup analyses presented in Table 2, SVR12 rates were significantly higher in the simeprevir group compared to the Control group.
*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.
As mentioned, given the high frequency of the Q80K polymorphism in the U.S. population and its significant negative impact on rates of SVR12, according to the prescribing information, the FDA is recommending that all Genotype 1a patients be screened for the Q80K polymorphism. Alternative treatment options should be considered for patients found to be infected with this polymorphic variant."
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
