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Asunaprevir? 6 years 6 months ago #13580

  • Serg
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Hi all!

I am in doubt about schema of therapy. 1b, compensated F4, TT/TG IL28b, high viral load, relapse after 48 weeks of peg/rib 10 years ago. Planning 24 weeks with sof/dac/rib or sof/led/rib using indian generics.

What is better for 1b compensated F4 with unfavorable predictors - dac or led? Is this correct that led is more effective for 1a and dac is more effective for 1b, due to their different "resistance" profiles?

In genotype 1b virus, BMS-790052 is significantly more active against the Y93H mutation (0.05 nM for BMS-790052 vs. 5 nM for GS-5885) [24]. In contrast, in genotype 1a, GS-5885 is 4–5 times more active against the M28T and Q30H mutations than BMS-790052, while the latter is approximately 2 times more potent against the L31M mutation.


What do you think about adding asunaprevir to the schema of therapy? Original asunaprevir (Sunvepra) is available in Russia at not very high price (200-250 USD per 4 weeks). From the one hand, preleminary 3-week triple therapy small study with asun shows impressive 100% SVR rate for some patients with favorable predictors and fast virologic responce, and, intuitively, 3 inhibitors may work better than two... But, from the other hand - these schemas with asun are not well-studied, and there are high chances of developing NS3/4 resistance in case of relapse from therapy with asun... If i will have NS3/4 resistance after relapse from therapy with asun - sof+simeprevir probably will be ineffective.

What do you think about it?
Thank you.
Probably infected in 1977
2005 - diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 - PegIFN/rib 48 weeks treatment, relapse
2016 - compensated F4, MELD 8-9, ALT 100-160
2018 - compensated F4, MELD 8, ALT 91

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Asunaprevir? 6 years 6 months ago #13586

Hi Serg,

24 weeks Sof/Led or Sof/Dac alone should give you a 99% SVR probability.
  • F4 is a weak negative predictor.
  • High viral load (assuming you are > 6 million) says definitely do 12 not 8
  • Past failure is your major issue as it drops the 97% SVR to 94% @12 weeks but this pulls up to 99% @ 24 weeks.

As you note there is a slightly different resistance profile for Led and Dac. You already have all your RAVs even if we can't measure them. These drugs are not mutagenic, they simple expose RAVs by selection.

Please note that the following advice has relatively little proven scientific basis (in trials data) but if you're going to do 24 weeks - and that is the right choice - then 12 weeks Sof+Dac and 12 weeks Sof+Led gives you 24 weeks Sof + exposure to 2 different NS5As, so if you have a few mutants left at the end of the first 12 weeks, the second 12 weeks should do the job on these stragglers.

1b is the easiest to clear, so you are looking at great odds without Asunaprevir.

Asunaprevir, like all NS3/4 agents, is a bit toxic. I would suggest keeping it up your sleeve as the Plan B if the 99% odds of 24 weeks of 2 DAAs don't work for you.

I would not bother with the Ribavirin. It will add little or nothing to your SVR probability on a 24 week treatment course, but it will make you suffer during treatment.

If you go here: fixhepc.com/hcv you will find a tool that contains the EASL and AASLD guidelines, but more importantly if you put in your numbers and then use the "Show Trials" button at the end of the results it will show you pretty much everything that is known in terms of hard data.
YMMV
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Asunaprevir? 6 years 6 months ago #13587

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Hi James! Thank you very much.

Yes, 8 weeks of therapy is not optimal in my case. Well, ribavirin will not add much for SVR probability... But this based on clinical trials with expensive original drugs (and, possible, with selected patients having good predictors). We cannot be completely sure in high quality of new dac/led indian generics yet (because we have no SVR statistics at this time)... Even without NS5A inhibitor, sof+rib may give some chances for SVR (48 week with sof+rib in cirrhotics may give more than 50% SVR - www.natap.org/2015/EASL/EASL_23.htm) And, AASLD recommends 12 week sof/led with riba (or 24 without riba) for F4 - this means that riba may have some positive effect in terms of SVR probability, at least for 12 week treatment...

It is interesting idea - to combine 12 week of sof+dac and 12 week of sof+led... I will think about it.

Thank you.

P.S. Great decision support tool!
Probably infected in 1977
2005 - diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 - PegIFN/rib 48 weeks treatment, relapse
2016 - compensated F4, MELD 8-9, ALT 100-160
2018 - compensated F4, MELD 8, ALT 91

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Asunaprevir? 6 years 6 months ago #13591

Do 24 weeks Sof + Dac, no Riba.

Riba will take 94% SVR for a prior treatment failure GT1 patient to 96% SVR on a 12 week treatment but given you can have 99% SVR with 24 weeks without Riba unless you (personally) need to save the money you as an individual patient are far better off running with 24 weeks.

We will publish the SVR data for generics on 16th April at EASL, but if you want to get started use the treatment advice above.

Glad you like the tool!
YMMV
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Asunaprevir? 6 years 6 months ago #13592

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Thanks. I will wait "real world" SVR statistics for NS5A indian generics before starting on 24 weeks.
Probably infected in 1977
2005 - diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 - PegIFN/rib 48 weeks treatment, relapse
2016 - compensated F4, MELD 8-9, ALT 100-160
2018 - compensated F4, MELD 8, ALT 91

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Asunaprevir? 6 years 6 months ago #13601

The doc knows. We will all know 4/17.
This email address is being protected from spambots. You need JavaScript enabled to view it.
forums.delphiforums.com/generichcvtx

G 1a F-1
Started tx 10/23/15 (Meso sof & led) ALT 48 AST 28 v/l 1.6 mil
11/17/15 4 wk lab ALT 17 AST 16 <15
11/18/15 Started Harvoni
12/16/15 8 wk lab ALT: 15 AST: 13 V/l UND
1/14/16 Fin. Tx
7/07/16 UND SVR 24

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Asunaprevir? 6 years 5 months ago #14179

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Yes. Also, i hope we will get some "self-reported" SVR data from russian-spoken forums in near future. Several patients on these forums already finished therapy with new indian NS5A generics, and it requires several weeks to get SVR data. Self-reported SVR data for indian licensed sofosbuvir generics (mostly, it seems, hepcinat and myhep) for 1b genotype looks good. I know about 2 reported relapses per approximately 100 svr's reported for genotype 1 (mostly 1b) for sof+dac (dac mostly based on chinese api) containing therapy. One of these two relapses, probably, occurs due to previous failure of dac+asun therapy and subsequent resistance. Both relapsers used generic sof from Egypt, not from India.
Probably infected in 1977
2005 - diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 - PegIFN/rib 48 weeks treatment, relapse
2016 - compensated F4, MELD 8-9, ALT 100-160
2018 - compensated F4, MELD 8, ALT 91
The following user(s) said Thank You: DrJames, LondonGirl

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