Drugs in Development: Phase 3 Genotype 1 — DAA plus PEG/RBV
mallani said
Sep 23, 2013
Hi guys,
I really don't want to start an argument, but the Pegasys vs Pegintron story is worth a mention. I was told by my doc that Pegasys (alpha 2a) was better tolerated and had better SVR rates than Pegintron (alpha 2b). On the Forum, this has been discussed previously, and Members achieved success (SVR) using both. There was disagreement about which one caused the worst side effects. I have now read at least 4 articles claiming SVR rates were better with Pegasys. Bob's link is another, and the Simeprevir Trial results makes 5. In the poor souls stuck with Peginterferon, perhaps it's worth a discussion with your doctor.
Sorry to be so hard on BMS. They obviously have no faith in their own NS-5B inhibitor BMS-791325. As a non-nucleotide inhibitor, it has little resistance to mutation (Sofosbuvir is a nucleotide analogue inhibitor). The Phase 2 Trials they did using this were OK, and I wonder why they have reverted to Peg/ Riba for the Phase 3 Trials. One of our Members, Karen (millercollaborative) has achieved SVR in the Phase 2 Trial using Asun/Daclat/BMS-791325.
Merck have a great drug in Victrelis. I'm sure it could be changed to twice daily dosing, and the 3 pills could be combined into one. It's safety profile is well known and it works!! I think it's been confined to the scrapheap too early. Why aren't they trialling MK-5172/Peg/Riba for the thousands of patients who have failed previous Rx with Victrelis or Incivek? It seems the big PharmCos want to keep all of the profits in-house, rather than co-operating with other companies to find the best ever combination.
Bills said
Sep 22, 2013
Hi Malcom
As Jill say's "as always" I think I'm going to give up trying to understand the information right off the press and wait till i hear it in English from you.
There is so much out there now in so many different stages it makes my head spin. Thanks so much for helping us along. As much as we have to rely on our doctors etc. to advise us on the best treatments available. Getting opinions from a fellow hep C sufferer with your understanding. gives us an edge to understand why a doctor may suggest one drug over another and what we may expect in symptoms and complications with other existing illnesses, understanding tests, why one combo is better for Geno 2 than 1 , cirrhotics vs not and naive vs relapsed etc.
I'm saying for the benefit of newcomers and to let them know how lucky we are to have some as yourself on this form.
Good luck fishing Malcom and thank you very much.
And Hi Jill
And this reminds me to help with $upport of this form.
Bills
Biggyb said
Sep 22, 2013
I am with Bills, makes my head spin. They say 2a over 2b (47% versus 41%) SVR rate.
-- Edited by Biggyb on Sunday 22nd of September 2013 02:56:44 PM
Cinnamon Girl said
Sep 22, 2013
Thanks for your comments, Malcolm, as always. I posted this as a broad overview for general information and appreciate you adding your intelligent and informed analysis.
I don`t really understand why Simeprevir has been given FDA priority review status, as it doesn`t seem to have any advantages over victrelis or incivek apart from maybe fewer side effects (certainly over incivek), and the fact that it`s a single pill per day, which is quite an improvement on the victrelis regimen especially. Or is it more to do with its potential use in combination with other drugs at some point? I notice it`s being studied in phase 2 trials in combination with NS5A blockers IDX719 (Samatasvir) and also Daclatasvir, in certain patient groups.
It`s good to see research continuing and phase 3 trials taking place, but there`s a long way to go yet, so it seems
mallani said
Sep 22, 2013
Hi Jill,
Thanks for the link. I realise that HCV Advocate is only passing these on and we are grateful they keep us up-to-date.
Some comments on the info:
Simeprevir: Please note that when they speak of 'relapsers', they are referring to patients who have relapsed after Peg/Riba treatments, not antiprotease relapsers. For treatment- naive patients, when you look closely at the results, the SVR figures are 85% for F0-1, dropping to 60% for the F4's. The IL28B status is also important with the CC's doing better. For some reason, the results found that patients using Peginterferon alpha-2a had a 10% better chance of SVR than those using Peginterferon alpha-2b. That's strange! Looking at the Sx, they don't appear to be much better than for Victrelis, with the added complication of raised bilirubin.
Sofosbuvir+Peg+Riba: I have not been able to find any SVR figures for an 8 week Rx duration. Gilead have been very close-lipped about Trials involving cirrhotics. Only the Neutrino Trial results have been released. Note, these were all treatment-naive patients. The 12 week Neutrino Trial claimed an overall SVR rate of 90%, with an 80% SVR for cirrhotics. Then they go on to say 'This compares favorably with the expected 60% SVR rate from SOC'. What!! Even for Rx-naive patients, the overall SVR rate for Geno 1 is only ~40% with SOC. I remain skeptical that 12 weeks Rx duration is enough.
Faldoprevir: Again, this is a second generation antiprotease, and as such, it should be better than Victrelis or Incivek. Rx duration is the same, with 24 weeks RGT, and 48 weeks if no RVR. Sx include raised bilirubin and rash. The results are pretty similar to Vict. and Inciv. It does much better in Geno 1b. Enough said.
Daclatasvir/Asunaprevir + Peg/Riba: Poor BMS. They are flogging a dead horse here. Trials show poor results for Geno 1a, but good in Geno 1b. We all agree that Daclatasvir is a good NS-5A blocker, but has a low barrier of resistance to mutations. They really need a good NS-5B blocker to use with it. Perhaps this study will help get approval for Daclatasvir, so Hepatologists can choose whether to use it with Sofosbuvir.
Overall, the second generation antiproteases are not exciting. The idea was that the pill dosing would be simplified ( which it has), they would have less Sx (maybe) and be effective against all Genotypes (apparently not). They supposedly would have a higher barrier to resistance (not proven-except for Merck's MK-5172). Incivek has been made easier with a twice daily dosing regime. What is Merck doing! Why aren't they aggressively trialling MS-5172! It's all getting too hard.
Cinnamon Girl said
Sep 21, 2013
Updated factsheet from the HCV Advocate website, September 2013.
Four new drug combos with Peg and Riba currently in phase 3 studies, for Genotype 1.
Hi guys,
I really don't want to start an argument, but the Pegasys vs Pegintron story is worth a mention. I was told by my doc that Pegasys (alpha 2a) was better tolerated and had better SVR rates than Pegintron (alpha 2b). On the Forum, this has been discussed previously, and Members achieved success (SVR) using both. There was disagreement about which one caused the worst side effects. I have now read at least 4 articles claiming SVR rates were better with Pegasys. Bob's link is another, and the Simeprevir Trial results makes 5. In the poor souls stuck with Peginterferon, perhaps it's worth a discussion with your doctor.
Sorry to be so hard on BMS. They obviously have no faith in their own NS-5B inhibitor BMS-791325. As a non-nucleotide inhibitor, it has little resistance to mutation (Sofosbuvir is a nucleotide analogue inhibitor). The Phase 2 Trials they did using this were OK, and I wonder why they have reverted to Peg/ Riba for the Phase 3 Trials. One of our Members, Karen (millercollaborative) has achieved SVR in the Phase 2 Trial using Asun/Daclat/BMS-791325.
Merck have a great drug in Victrelis. I'm sure it could be changed to twice daily dosing, and the 3 pills could be combined into one. It's safety profile is well known and it works!! I think it's been confined to the scrapheap too early. Why aren't they trialling MK-5172/Peg/Riba for the thousands of patients who have failed previous Rx with Victrelis or Incivek? It seems the big PharmCos want to keep all of the profits in-house, rather than co-operating with other companies to find the best ever combination.
Hi Malcom
As Jill say's "as always" I think I'm going to give up trying to understand the information right off the press and wait till i hear it in English from you.
There is so much out there now in so many different stages it makes my head spin. Thanks so much for helping us along. As much as we have to rely on our doctors etc. to advise us on the best treatments available. Getting opinions from a fellow hep C sufferer with your understanding. gives us an edge to understand why a doctor may suggest one drug over another and what we may expect in symptoms and complications with other existing illnesses, understanding tests, why one combo is better for Geno 2 than 1 , cirrhotics vs not and naive vs relapsed etc.
I'm saying for the benefit of newcomers and to let them know how lucky we are to have some as yourself on this form.
Good luck fishing Malcom and thank you very much.
And Hi Jill
And this reminds me to help with $upport of this form.
Bills
I am with Bills, makes my head spin. They say 2a over 2b (47% versus 41%) SVR rate.
a 2010 report.
http://www.ncbi.nlm.nih.gov/pubmed/20187106
-- Edited by Biggyb on Sunday 22nd of September 2013 02:56:44 PM
Thanks for your comments, Malcolm, as always. I posted this as a broad overview for general information and appreciate you adding your intelligent and informed analysis.
I don`t really understand why Simeprevir has been given FDA priority review status, as it doesn`t seem to have any advantages over victrelis or incivek apart from maybe fewer side effects (certainly over incivek), and the fact that it`s a single pill per day, which is quite an improvement on the victrelis regimen especially. Or is it more to do with its potential use in combination with other drugs at some point? I notice it`s being studied in phase 2 trials in combination with NS5A blockers IDX719 (Samatasvir) and also Daclatasvir, in certain patient groups.
It`s good to see research continuing and phase 3 trials taking place, but there`s a long way to go yet, so it seems
Hi Jill,
Thanks for the link. I realise that HCV Advocate is only passing these on and we are grateful they keep us up-to-date.
Some comments on the info:
Simeprevir: Please note that when they speak of 'relapsers', they are referring to patients who have relapsed after Peg/Riba treatments, not antiprotease relapsers. For treatment- naive patients, when you look closely at the results, the SVR figures are 85% for F0-1, dropping to 60% for the F4's. The IL28B status is also important with the CC's doing better. For some reason, the results found that patients using Peginterferon alpha-2a had a 10% better chance of SVR than those using Peginterferon alpha-2b. That's strange! Looking at the Sx, they don't appear to be much better than for Victrelis, with the added complication of raised bilirubin.
Sofosbuvir+Peg+Riba: I have not been able to find any SVR figures for an 8 week Rx duration. Gilead have been very close-lipped about Trials involving cirrhotics. Only the Neutrino Trial results have been released. Note, these were all treatment-naive patients. The 12 week Neutrino Trial claimed an overall SVR rate of 90%, with an 80% SVR for cirrhotics. Then they go on to say 'This compares favorably with the expected 60% SVR rate from SOC'. What!! Even for Rx-naive patients, the overall SVR rate for Geno 1 is only ~40% with SOC. I remain skeptical that 12 weeks Rx duration is enough.
Faldoprevir: Again, this is a second generation antiprotease, and as such, it should be better than Victrelis or Incivek. Rx duration is the same, with 24 weeks RGT, and 48 weeks if no RVR. Sx include raised bilirubin and rash. The results are pretty similar to Vict. and Inciv. It does much better in Geno 1b. Enough said.
Daclatasvir/Asunaprevir + Peg/Riba: Poor BMS. They are flogging a dead horse here. Trials show poor results for Geno 1a, but good in Geno 1b. We all agree that Daclatasvir is a good NS-5A blocker, but has a low barrier of resistance to mutations. They really need a good NS-5B blocker to use with it. Perhaps this study will help get approval for Daclatasvir, so Hepatologists can choose whether to use it with Sofosbuvir.
Overall, the second generation antiproteases are not exciting. The idea was that the pill dosing would be simplified ( which it has), they would have less Sx (maybe) and be effective against all Genotypes (apparently not). They supposedly would have a higher barrier to resistance (not proven-except for Merck's MK-5172). Incivek has been made easier with a twice daily dosing regime. What is Merck doing! Why aren't they aggressively trialling MS-5172! It's all getting too hard.
Updated factsheet from the HCV Advocate website, September 2013.
Four new drug combos with Peg and Riba currently in phase 3 studies, for Genotype 1.
http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Phase_3_Genotype_1.pdf