Forum Replies Created
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Regarding simeprevir ..
It is my understanding that Janssen uses simeprevir sodium in their branded Olysio, Sovriad and Galexos capsules. The simeprevir API currently available from China is not the sodium salt and therefor of questionable use.
The linked disclosure of a cardiotoxic impurity (Related Substance C) present in the simeprevir manufacturing process poses a greater complexity.
From my reading – Johnson & Johnson (Janssen) has been seeing a substantial decrease in demand for this medicine. Aside from the recommended use in retreatment – is there a market for simeprevir based medicines sufficient to warrant the development of a generic ??
Certainly J&J has studied this ad nauseam – curious to know what folks here are seeing in the real world.
J
PS: Note that simeprevir (Olysio) is part of my upcoming retreatment plan. Current retail price here in the States is $22,500 USD for 28 capsules (150 mg). 24 weeks makes for $135,000 for this component alone. Outrageous ..
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 UndetectedThanks for posting this. Have been reading most all the material available online regarding HCV retreatment. The collection of work presented here by David Wyles MD at UCSD is interesting to be sure.
From the perspective of a patient seeking retreatment – I view information such as this as very encouraging – though academic.
Using the existing AASLD guidelines for initial therapy – medical coverage here in the States for approved HCV DAA medicines is often denied to patients without significant fibrosis scores.
Following the new and current AASLD guidelines for retreatment – “deferral of treatment” is recommended for patients who do not have cirrhosis and do not have reasons for urgent retreatment.
http://www.hcvguidelines.org/full-report/retreatment-persons-whom-prior-therapy-has-failed
Most any retreatment plan using approved HCV medicines here will be unavailable through medical insurance with the existing guidelines and drug costs – emphasis on the latter.
Using the flow chart shown above from Wyles’ presentation – the most basic retreatment option (no NS5A RAVs) calls for 24 weeks of Harvoni – current retail price here is just over $183,000 USD. The base retreatment option when some known NS5A RAVs are present calls for 24 weeks of Sovaldi and Olysio with ribavirin – current retail price here is over $305,000 USD.
While government agencies and insurers have negotiated significant price discounts from the drug manufacturers – these reduced prices are not available to individual patients seeking treatment.
Any realistic retreatment regiment is thereby limited to available generic medicines. This means that new drug studies – however promising – will only produce practical results sometime in the future when and if such medicines are manufactured as generics. Note that Olysio (simeprevir) – currently recommended for retreatment – has yet to become readily available as a generic.
Crossing the first hurdle for treatment has only just recently become a reality for many with the availability of generics. The second hurdle for retreatment is somewhat higher making resources such as FixHepC and access to affordable generic medicines even more important.
J
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 Undetectedklhilde wrote:The benefit of adding ribavirin to retreatment is not exclusive to NS5A inhibitors. In a small study of patients for whom a protease inhibitor regimen had failed, most patients were retreated with a protease inhibitor–containing regimen (ombitasvir/paritaprevir/ritonavir plus dasabuvir) plus sofosbuvir and ribavirin. Fourteen of these 15 patients achieved SVR12.
Am I reading that correctly? They used two different NS5B inhibitors together? (Sofosbuvir and Dasabuvir)
Yes – I believe you are correct – in part. Sofosbuvir is characterized as a nucleotide polymerase inhibitor.
This looks like the AbbVie Quartz-1 study where they added Sofosbuvir to their existing Viekira Pak plus RBV regiment (12 weeks).
Some of the details here:
Note the size of the study group – it is indeed very small.
J
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 UndetectedJonathan
Curious about your progress – please check your PM
J.
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 UndetectedJonathan
Have read your posts here and am very sorry that you too failed to achieve SVR – our cases are indeed similar.
Interesting that you had NS5A resistance testing done before your GZP/EBR therapy – suppose it was part of the Merck trial.
And yes – I had NS3/4A resistance tested. Luckily – against the four readily available protease inhibitors – there were no RAVs detected (note that treatment significant baseline NS3 RAVs are rare). Dodged the prevalent Q80K (present in > 40% of GT 1a patients here) – so it looks like the effectiveness of simeprevir will not be impaired. Have read that there is no clear impact of Q80K on extended simeprevir/sofosbuvir therapy anyway.
I too have also read about the durability of treatment emergent NS5A RAVs. Unlike the NS3 mutations (such as Q80K that fade in ~ 72 weeks) – treatment emergent NS5A RAVs (like Q30R) soldier on well past 96 weeks (the extent of most tests to date). This is another reason that the next course of treatment after DAA failure needs to be carefully chosen.
You have probably studied most of the retreatment options by now. I see that Dr. Freeman just posted a link to another current AASLD hosted article on the subject. The bottom line seems the same on most I have read.
Curious as to your thought on adding daclatasvir to your gastroenterologist’s AASLD based treatment recommendation. It looks like a recent recommendation I have seen for “desperation time” where both serious NS3 and NS5A RAV’s are present (R155, A156, D16
. Would be extremely cautious about throwing everything in the mix – though I can understand the desire to do so.The more I read on retreatment – the more inclined I am to wait awhile longer – maybe just a year. There are a number of potent NS5A inhibitors on the horizon that look very promising. And those existing emergent RAV’s should be easier to deal with by then just with time alone. Will see – waiting isn’t my strong suit.
I wish you the best Jonathan – please keep us posted on your progress. Greatly looking forward to your success story.
And I need to add this for others who are seeking treatment ..
The success rate in achieving SVR with existing DAA therapies of the type available here-and-now is remarkably high – have witnessed it first-hand. Only a very few of us are unfortunate enough to miss on the first attempt – and with the advances in HCV DAA therapies coming so quickly now – there will soon be a day where we are all free of this.
Have been reluctant to post about my lack of success this go-round – concerned that others might become overly worried when they really shouldn’t be. Most everyone will beat this now first try – and I will catch up with them soon.
Probably before I wear-out the new set of tires on my motorcycle – California coast and sunny days ahead.
J.
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 UndetectedJonathan
I did not have HCV drug resistance testing performed prior to my therapy (Viekira/RBV) – hence no baseline data for RAVs.
Subsequent HCV drug resistance testing by LabCorp (Monogram Biosciences) shows an NS5A Q30R RAV and resistance to both ledipasvir and ombitasvir. Without prior testing – I have no way to be sure that this RAV is treatment emergent.
While taking Viekira/RBV – I did experience early viral suppression. Started with a modest 500k VL that went to undetected within 12 days and remained undetected through the 12 week course of therapy. AST/ALT also dropped from ~ 60/100 to a remarkable 13/11 within the first 12 days of therapy – the lowest numbers I had seen in over 40 years.
Side effects during treatment were negligible – if even present. Actually felt much better during treatment than before – or certainly after.
The success was short lived. Testing at EOT plus 12 weeks showed a 2,240k VL and LFTs headed back to pretreatment levels.
Covered most of this in my first post on this forum a week ago – sorry to be repetitive here.
By simply following the AASLD recommendations for retreatment – or those outlined in the article Dr. Freeman recently posted (authored by Dr. Jordan Feld just last month) – I would be back to watchful waiting in the hope that new medicines and treatment protocols would soon appear.
Having waited for decades – and coming so close while experiencing a wonderful but brief respite – I suppose my desire to try another therapy is understandable – even if misguided. My GI is willing to support my decision to go forward with the simeprevir/sofosbuvir + RBV …. I have to admit to second thoughts though. Have read a number of articles covering the increase of RAVs with unsuccessful retreatment protocols.
You mentioned undergoing additional resistance testing – curious as to your strategy. I was thinking about another NS5A resistance assy that includes daclatasvir (Quest Diagnostics) – not sure if it would be helpful – will discuss it with the treating physician should I go forward.
Stalled here at the moment.
All the best
J.
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 UndetectedKnowing his original post here is somewhat dated – I can not help but wonder if Jonathan successfully pursued retreatment. Hopefully he will comment when he comes back online.
My situation is somewhat similar – Viekira/RBV failure (as previously posted). And my gastroenterologist is also directing me towards the AASLD recommendation for retreatment with simeprevir/sofosbuvir and RBV.
It seems there may not be an experience based consensus for DAA retreatment – maybe because it is all too new. In lieu of a better recommendation – I am inclined to follow my GI’s advice.
I do see that Mesochem lists simeprevir on their website – not sure what that means in terms of real-world availability.
Will explore this and other possible retreatment options during my upcoming GP2U appointment.
J
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 UndetectedThanks Vororo for posting that study – I certainly can use every thought on this.
I actually tried to decipher that article awhile back – it does appear that daclatasvir is well studied and effective when paired with sofosbuvir.
Current AASLD guidelines for retreatment in my case specify the simeprivir/sofosbuvir + RBV mix. And my GI here agrees with this. Note that this also shows-up on FixHepC’s HCV Decision Support Tool – referencing AASLD guidelines and the COSMOS study.
Unfortunately – daclatasvir was not included in the NS5A drug resistance testing I had performed – most likely since it is relatively new. Certainly – the labs will include it in future testing.
Will discuss this and all options with Dr. Freeman – however – I am somewhat worried about this next step. It seems that retreatment after DAA failure may have consequences – and the choice of medicines has to be made very carefully. Found this ….
__________“One concern is that failure of a regimen that contains an NS5A inhibitor (ledipasvir in Harvoni, ombitasvir in Viekira Pak / Viekira) may result in the emergence of NS5A-resistant virus that can take up to 96 weeks to disappear.
NS5A inhibitors may have some activity against these variants, but further treatment with an NS5A inhibitor could result in higher-level resistance if hepatitis C is not rapidly suppressed. Adding an agent of a new class could increase antiviral activity.”
The next step looks challenging.
Cheers
John
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 UndetectedThanks kindly for all your replies.
After trying to arrange an appointment on GP2U without success – I forwarded an email as Gaj suggested. Will be looking for a reply with great anticipation.
As to Viekira Pak – I have read the FDA warning that was issued subsequent to my treatment. Since my hepatic status has not progressed to cirrhosis, the risk of liver injury in my case was minimal. Administered under the new guidelines – Viekira Pak appears to be relatively safe and very effective.
Given the choice – I would have chosen Harvoni – if only to avoid the additional ribavirin (which I historically tolerate well). But in the end – my treatment with Harvoni would have likely failed as well – as shown by the presence of the NS5A Q30R RAV in my subsequent resistance tests.
So I have taken the first small steps towards retreatment – starting with my first post here. Will certainly post again as things progress.
Have to believe that I will find a way to finally beat this.
All the best.
John
GT 1a (~196
Diagnosed Non A/B ’85 – HCV ‘89
Rebetron INF/RBV 17 months 2000 – Failure
Infergen INF/RBV 11 months 2002 – Failure
Viekira Pak + RBV 12 weeks 2015 – Failure
VL Und at +3 weeks > EOT – EOT+12 weeks 2,240k
Resistance Tests – NS5a Q30R
SMV/DCV/SOF + RBV 24 weeks 2016
VL Det <15 +2 and +4 weeks – Und +8 weeks > EOT
SVR4, SVR12 and SVR24 Undetected
