Aa
Boceprevir --Phase 2 EASL Results
http://www.reuters.com/article/marketsNews/idINN2332156320090423?rpc=44
UPDATE 2-Schering hepatitis C drug shines, but anemia seen
Thu Apr 23, 2009 11:09am EDT
* Virus undetectable in 75 pct of treated patients
* Best response seen for any drug in mid-stage trials
* But anemia seen in half of treated patients
* 39 to 51 pct of treated patients needed EPO for anemia
By Ransdell Pierson
NEW YORK, April 23 (Reuters) - A Schering-Plough Corp (SGP.N) drug knocked the hepatitis C virus down to undetectable levels in three-fourths of patients in a mid-stage study, twice the effectiveness seen with standard treatments, researchers said on Thursday.
But half the patients taking the boceprevir experimental medicine developed anemia -- a potential commercial disadvantage to a similar pill called telaprevir that Vertex Pharmaceutical Inc (VRTX.O) is developing.
Both drugs work through a new mechanism -- by blocking a protein called protease that the virus needs to replicate -- and are considered potential big-selling products. As many as 4 million Americans are believed to be infected with the virus, the leading reason for liver transplants.
Results of the Phase II boceprevir trial, involving 595 patients who were infected with the virus but had not previously been treated, were presented in Copenhagen at the annual meeting of the European Association for the Study of the Liver. Patients had genotype 1, the most common form of the virus.
During the first month of the study, all patients received the two standard hepatitis C treatments sold by Schering-Plough -- a long-acting form of interferon called Pegintron and the anti-viral pill ribavirin.
One group of patients then added boceprevir to Pegintron and ribavirin for 44 weeks, while another group took only Pegintron and ribavirin over the same period.
After the 48-week trial concluded, 75 percent of those in the boceprevir group had a sustained virologic response (SVR) -- meaning undetectable levels of virus.
"This is the highest sustained virologic response reported for any Phase II study of patients with genotype 1," said Dr. Paul Kwo, an associate professor at Indiana University School of Medicine, the study's chief investigator.
By contrast, only 38 percent of patients who did not get boceprevir drove the virus down to undetectable levels in the same 48-week period.
Researchers also determined that after only 28 weeks of treatment with boceprevir, Pegintron and ribavirin, 56 percent of patients achieved SVR.
Anemia was seen in about half of patients taking boceprevir, and in a third of patients taking only Pegintron and ribavirin.
page 2
Erythropoietin (EPO), a widely used anemia treatment, was used by 39 percent to 51 percent of patients taking boceprevir, and by 26 percent of those taking only Pegintron and ribavirin.
"Management of anemia with EPO is a common practice in hepatitis C treatment today," said Kwo, who noted that ribavirin and protease inhibitors both increase the risk of anemia.
A lesser incidence of anemia was reported last year for Vertex' rival telaprevir in mid-stage trials -- ranging from 29 to 37 percent of patients. Telaprevir knocked the virus to undetectable levels in about two thirds of patients.
Kwo, who has also tested the Vertex product, said data from late-stage trials of boceprevir and telaprevir will provide a clearer indication of relative anemia risk for the two new protease inhibitors.
Geoffrey Porges, a biotech analyst for Sanford Bernstein who is attending the Copenhagen meeting, said the need to take EPO to control anemia will hurt boceprevir.
"It would be very unusual for a drug to go forward and more or less require the use of another drug that's not even approved for that indication," Porges said.
Boceprevir is considered one of the most important of Schering-Plough's experimental drugs. Merck & Co (MRK.N) will inherit the pill when it completes its planned purchase of Schering later this year.
Shares of Merck were down 0.57 percent to $22.85, while Schering-Plough fell 0.14 percent to $21.64, both in late morning trading on the New York Stock Exchange.
(Additional reporting by Bill Berkrot) (Reporting by Ransdell Pierson; Editing by Lisa Von Ahn and Gunna Dickson)
UPDATE 2-Schering hepatitis C drug shines, but anemia seen
Thu Apr 23, 2009 11:09am EDT
* Virus undetectable in 75 pct of treated patients
* Best response seen for any drug in mid-stage trials
* But anemia seen in half of treated patients
* 39 to 51 pct of treated patients needed EPO for anemia
By Ransdell Pierson
NEW YORK, April 23 (Reuters) - A Schering-Plough Corp (SGP.N) drug knocked the hepatitis C virus down to undetectable levels in three-fourths of patients in a mid-stage study, twice the effectiveness seen with standard treatments, researchers said on Thursday.
But half the patients taking the boceprevir experimental medicine developed anemia -- a potential commercial disadvantage to a similar pill called telaprevir that Vertex Pharmaceutical Inc (VRTX.O) is developing.
Both drugs work through a new mechanism -- by blocking a protein called protease that the virus needs to replicate -- and are considered potential big-selling products. As many as 4 million Americans are believed to be infected with the virus, the leading reason for liver transplants.
Results of the Phase II boceprevir trial, involving 595 patients who were infected with the virus but had not previously been treated, were presented in Copenhagen at the annual meeting of the European Association for the Study of the Liver. Patients had genotype 1, the most common form of the virus.
During the first month of the study, all patients received the two standard hepatitis C treatments sold by Schering-Plough -- a long-acting form of interferon called Pegintron and the anti-viral pill ribavirin.
One group of patients then added boceprevir to Pegintron and ribavirin for 44 weeks, while another group took only Pegintron and ribavirin over the same period.
After the 48-week trial concluded, 75 percent of those in the boceprevir group had a sustained virologic response (SVR) -- meaning undetectable levels of virus.
"This is the highest sustained virologic response reported for any Phase II study of patients with genotype 1," said Dr. Paul Kwo, an associate professor at Indiana University School of Medicine, the study's chief investigator.
By contrast, only 38 percent of patients who did not get boceprevir drove the virus down to undetectable levels in the same 48-week period.
Researchers also determined that after only 28 weeks of treatment with boceprevir, Pegintron and ribavirin, 56 percent of patients achieved SVR.
Anemia was seen in about half of patients taking boceprevir, and in a third of patients taking only Pegintron and ribavirin.
page 2
Erythropoietin (EPO), a widely used anemia treatment, was used by 39 percent to 51 percent of patients taking boceprevir, and by 26 percent of those taking only Pegintron and ribavirin.
"Management of anemia with EPO is a common practice in hepatitis C treatment today," said Kwo, who noted that ribavirin and protease inhibitors both increase the risk of anemia.
A lesser incidence of anemia was reported last year for Vertex' rival telaprevir in mid-stage trials -- ranging from 29 to 37 percent of patients. Telaprevir knocked the virus to undetectable levels in about two thirds of patients.
Kwo, who has also tested the Vertex product, said data from late-stage trials of boceprevir and telaprevir will provide a clearer indication of relative anemia risk for the two new protease inhibitors.
Geoffrey Porges, a biotech analyst for Sanford Bernstein who is attending the Copenhagen meeting, said the need to take EPO to control anemia will hurt boceprevir.
"It would be very unusual for a drug to go forward and more or less require the use of another drug that's not even approved for that indication," Porges said.
Boceprevir is considered one of the most important of Schering-Plough's experimental drugs. Merck & Co (MRK.N) will inherit the pill when it completes its planned purchase of Schering later this year.
Shares of Merck were down 0.57 percent to $22.85, while Schering-Plough fell 0.14 percent to $21.64, both in late morning trading on the New York Stock Exchange.
(Additional reporting by Bill Berkrot) (Reporting by Ransdell Pierson; Editing by Lisa Von Ahn and Gunna Dickson)
gd: ay', and just think of the impending confusion in cocktail choices, Dr X prescribe daily sex-on-the-beach but Dr Y favors a sloe-screw, what's a poor patient to do?
willy: it's interesting to compare the arms of the ongoing phase III trials for TV and BC and the phase II for R7128. No one's trying to skimp on the RBV anymore. Vertex seems interested in limiting TV exposure, probably because of the stronger AEs. Schering isn't flinching at prescribing BC for the duration. Roche is checking on dosage (500 vs 1000mg). All three also want to check whether 24w is good enough, and all are big trials.
With the Phase III trials full, the R7128 trial looks like the best option for naive g1s choosing tx at the moment. Looking ahead, it would be great to have some way to add R7128 after TV/BC approval but unless something changes that seems out of reach for four more years or so. Here's a much more detailed description of the R7128/R7227 (Inform-1) trial than given in abstract 263 above:
http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9MzIzMnxDaGlsZElEPS0xfFR5cGU9Mw==&t=1
Slide 15 shows the VL drop for all 8 patients in the 1000/200 arm : to und in 14 days with no ifn/rbv with one breakthrough (likely mopped up with some ifn.._)
andiamo: Vertex definitely did a much better job of data collection on its relapse/nr trial than Schering, whose results ended up being uninterpretable. I doubt there's any underlying difference in the effect of the two drugs but it would be great to see Vertex qualify for early approval on the basis of its prove3 data.
willy: it's interesting to compare the arms of the ongoing phase III trials for TV and BC and the phase II for R7128. No one's trying to skimp on the RBV anymore. Vertex seems interested in limiting TV exposure, probably because of the stronger AEs. Schering isn't flinching at prescribing BC for the duration. Roche is checking on dosage (500 vs 1000mg). All three also want to check whether 24w is good enough, and all are big trials.
With the Phase III trials full, the R7128 trial looks like the best option for naive g1s choosing tx at the moment. Looking ahead, it would be great to have some way to add R7128 after TV/BC approval but unless something changes that seems out of reach for four more years or so. Here's a much more detailed description of the R7128/R7227 (Inform-1) trial than given in abstract 263 above:
http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9MzIzMnxDaGlsZElEPS0xfFR5cGU9Mw==&t=1
Slide 15 shows the VL drop for all 8 patients in the 1000/200 arm : to und in 14 days with no ifn/rbv with one breakthrough (likely mopped up with some ifn.._)
andiamo: Vertex definitely did a much better job of data collection on its relapse/nr trial than Schering, whose results ended up being uninterpretable. I doubt there's any underlying difference in the effect of the two drugs but it would be great to see Vertex qualify for early approval on the basis of its prove3 data.
Re thinking my position on
'Being thankful to have HVC'
Well, maybe not... but without hcv I never would have known about new PI's development.
My VRTX has gone up almost 10 pts since Thanksgiving purchase, and my SGP is also doing good.
Hopefully these new PI drugs will eradicate HCV once and for all.
And like the good American capitalist I am, just loving being able to profit from this.
apache
'Being thankful to have HVC'
Well, maybe not... but without hcv I never would have known about new PI's development.
My VRTX has gone up almost 10 pts since Thanksgiving purchase, and my SGP is also doing good.
Hopefully these new PI drugs will eradicate HCV once and for all.
And like the good American capitalist I am, just loving being able to profit from this.
apache
I am pretty sure the stock price is increasing due to the expectation that Vertex will be given early approval for treatment failures only, based on the data released at EASL. There was a dramatic increase in volume of "call" options the day after the data on Prove 3 was published.
I think cocktails will be the future for many of us.
I've heard it's like pouring gasoline on a fire :)
I've heard it's like pouring gasoline on a fire :)
btw, since log base 10 is what is usually quoted, a one log drop is a ten fold vl reduction.
----------------------------------------------------
Ya know I quoted someone who should know..... and on the way home I started thinking about that and thought that it had to be wrong but I'm about 90% sure I understood that properly..... but that you are right. It was on a webcast and I don't think it is available any more but I'll take a look. You are right of course; no argument.
So far as the trial.......
PI's + IFN or
PI's + RBV or
PI's + IFN + RBV
Simply 2 PI's; no SOC
Then there could also be dosing arms to figure the optimal dosing; whew!!
It could be any or all. BUT........ remember what happened when people were exposed to TVR + IFN but no ribaviren? = 60% failure and they may have resistance issues. The deal is....these drugs will be potent and will cure some people; maybe a lot but I think I'd prefer to be in a 2b trial or a Phase 3 trial.
Unfortunately any trial that takes place in 2009 will likely have a both a SOC control arm and could also have a TVR/SOC *second* control arm. I would venture a guess that after TVR is approved we may lose the SOC (IFN & RBV) arm.
best,
Willy
----------------------------------------------------
Ya know I quoted someone who should know..... and on the way home I started thinking about that and thought that it had to be wrong but I'm about 90% sure I understood that properly..... but that you are right. It was on a webcast and I don't think it is available any more but I'll take a look. You are right of course; no argument.
So far as the trial.......
PI's + IFN or
PI's + RBV or
PI's + IFN + RBV
Simply 2 PI's; no SOC
Then there could also be dosing arms to figure the optimal dosing; whew!!
It could be any or all. BUT........ remember what happened when people were exposed to TVR + IFN but no ribaviren? = 60% failure and they may have resistance issues. The deal is....these drugs will be potent and will cure some people; maybe a lot but I think I'd prefer to be in a 2b trial or a Phase 3 trial.
Unfortunately any trial that takes place in 2009 will likely have a both a SOC control arm and could also have a TVR/SOC *second* control arm. I would venture a guess that after TVR is approved we may lose the SOC (IFN & RBV) arm.
best,
Willy
I suppose it all depends on how long you're prepared to wait but r7128 approval (2013?) is already looking too long for me and anything further out seems a bit of a blur.
Best wishes for Vertex stockholders on the J&J buyout, but even if VCH222 is promising it looks a long way out. What Vertex presented last Sat. in Copenhagen were first results in human testing :
http://www.kenes.com/easl2009/Posters/Abstract821.htm
preliminary phase I testing. Meanwhile r7128 has been gathering successful results for a while and is just starting a 400 patient worldwide phase II, scheduled to complete around the time TV and BC get approval. In their phase III design one would hope they'd choose to compare ifn/rbv/ns3 against ifn/rbv/ns3/r7128. If they instead compare ifn/rbv vs ifn/rbv/r7128 it might be hard to find participants...
as for Pharmasset's next contender, psi7851, it looks great, but, uh, might be dead by then...here's a nice detailed summary of the trial and error work that went into impoving r7128:
http://www.pharmasset.com/download/VRUS-R7128-HCVDrugDiscovery-CHI-042828.pdf
btw, since log base 10 is what is usually quoted, a one log drop is a ten fold vl reduction.
Best wishes for Vertex stockholders on the J&J buyout, but even if VCH222 is promising it looks a long way out. What Vertex presented last Sat. in Copenhagen were first results in human testing :
http://www.kenes.com/easl2009/Posters/Abstract821.htm
preliminary phase I testing. Meanwhile r7128 has been gathering successful results for a while and is just starting a 400 patient worldwide phase II, scheduled to complete around the time TV and BC get approval. In their phase III design one would hope they'd choose to compare ifn/rbv/ns3 against ifn/rbv/ns3/r7128. If they instead compare ifn/rbv vs ifn/rbv/r7128 it might be hard to find participants...
as for Pharmasset's next contender, psi7851, it looks great, but, uh, might be dead by then...here's a nice detailed summary of the trial and error work that went into impoving r7128:
http://www.pharmasset.com/download/VRUS-R7128-HCVDrugDiscovery-CHI-042828.pdf
btw, since log base 10 is what is usually quoted, a one log drop is a ten fold vl reduction.
Vertex is up 9% today and was up about 6% yesterday. Why? Well, one rumor is that J and J is going to buy it. One other reason is the results at EASL.
The "Stat C" type TX; dual PI's is looking more and more like the wave of the future. Vertex is well poised to meet that type of treatment. It clearly has the lead protease inhibitor (IMHO). When it acquired VCH-222 it may have also bought the lead polymerase inhibitor. The 4 day monotherapy results for each was 3.6 and 3.7 log respectably. Josh Boger of Vertex has said that they combine beautifully and they will produce a log drop in viral load that is "additive and synergistic". That means in theory one could see at minimum a 7.3 log reduction in days. The beauty is that each compound covers the cross resistance issue that the other may possess. In theory it will be tough for the virus to have an escape route.
Keep also in mind..... here is what is maintained about the 2nd generation drug;
-----------------------
"PSI-7851 has demonstrated in vitro anti-HCV activity with EC(50) values of 90 +/- 60 nM, which is approximately 15- to 20-fold more potent than the active metabolite of Pharmasset's first generation nucleoside polymerase inhibitor, R7128.
---------------------------
Each log reduction that a compound produces equals a 100 fold reduction in viral load. This is where we will have to compare the compounds; *in logs*. Further, they also have to combine well; for instance combining teleprevir and boceprevir would be useless; they are both strong in the same area and are weak on certain mutant variants. In addition to covering a broad spectrum the compounds must be survive toxicology results; I think some are metaboliszed in different areas of the body so for instance to not overload one organ. We are seeing that many compounds are having a tough time geting one compound to be effective and non-toxic. It is a long way to go to get 2 that combine well. I think Vertex may have one. I think the stock market may think so too.
Vertex expects to go to trials with Teleprevir and VCH-222 in combination late 2009; possibly also with arms with riba only, IFN only and the 4 compounds together.
My opinion is that the combo may be highly effective just as dual therapy..... but remember that HCV RNA likes to "hide" in scar tissue and may still take some extended treatment to completely rid the body of it. IF there is any cross resistance issue mere dual PI's may not be enough to de-throne the king. They should dramatically reduce the need for exposure to SOC and to hear Vertex talk about it Interferon is the culprit that affects most people long term post TX.
got to run,
Willy
The "Stat C" type TX; dual PI's is looking more and more like the wave of the future. Vertex is well poised to meet that type of treatment. It clearly has the lead protease inhibitor (IMHO). When it acquired VCH-222 it may have also bought the lead polymerase inhibitor. The 4 day monotherapy results for each was 3.6 and 3.7 log respectably. Josh Boger of Vertex has said that they combine beautifully and they will produce a log drop in viral load that is "additive and synergistic". That means in theory one could see at minimum a 7.3 log reduction in days. The beauty is that each compound covers the cross resistance issue that the other may possess. In theory it will be tough for the virus to have an escape route.
Keep also in mind..... here is what is maintained about the 2nd generation drug;
-----------------------
"PSI-7851 has demonstrated in vitro anti-HCV activity with EC(50) values of 90 +/- 60 nM, which is approximately 15- to 20-fold more potent than the active metabolite of Pharmasset's first generation nucleoside polymerase inhibitor, R7128.
---------------------------
Each log reduction that a compound produces equals a 100 fold reduction in viral load. This is where we will have to compare the compounds; *in logs*. Further, they also have to combine well; for instance combining teleprevir and boceprevir would be useless; they are both strong in the same area and are weak on certain mutant variants. In addition to covering a broad spectrum the compounds must be survive toxicology results; I think some are metaboliszed in different areas of the body so for instance to not overload one organ. We are seeing that many compounds are having a tough time geting one compound to be effective and non-toxic. It is a long way to go to get 2 that combine well. I think Vertex may have one. I think the stock market may think so too.
Vertex expects to go to trials with Teleprevir and VCH-222 in combination late 2009; possibly also with arms with riba only, IFN only and the 4 compounds together.
My opinion is that the combo may be highly effective just as dual therapy..... but remember that HCV RNA likes to "hide" in scar tissue and may still take some extended treatment to completely rid the body of it. IF there is any cross resistance issue mere dual PI's may not be enough to de-throne the king. They should dramatically reduce the need for exposure to SOC and to hear Vertex talk about it Interferon is the culprit that affects most people long term post TX.
got to run,
Willy
completely agree about r1728, and though I know that any drinking is staunchly opposed around here, I think cocktails will be the future for many of us. The main issue to my mind is how long can one wait, or using dointime's phrase, how much liver-time do you have left?
Though R7128 is the best bet out there approval seems to be moving at a very deliberate space. Phase II trials are now *starting* to recruit world wide and won't complete until 2011 (clinicaltrials.gov id NCT00869661) Assuming the definition of SOC immediately changes to ifn/rbv/ns3-pi the day either tv or bc get fda approval, trying to enroll in the Roche/Pharmasset phase III for r7128 would be a good shot. Otherwise the best bet for a late 2010/2011 departure is likely to ntz(alinia)/ifn/rbv/ns3pi with a SAMe chaser.
Some may be prepared to wait for R7128 approval before txing, but that seems a ways out. The frustrating part of this, IMHO opinion, is that our proprietary/competitive model of drug-development works very well when it's an issue of A or B as per the current Schering/Vertex fight, but works poorly when the optimal strategy is A and B, something that would require more cooperation than competition.
For example, though it's been obvious for years that polymerase/protease combos are the way to go, we had to wait until abstract 263 above to have this tested in human. Even then, the combo tests only get done after one company has managed to acquire both types of PI, as Vertex recently did. Meanwhile, the evident first choice from a patient's perspective, R7128 with tv or bc, doesn't get tested.
Though R7128 is the best bet out there approval seems to be moving at a very deliberate space. Phase II trials are now *starting* to recruit world wide and won't complete until 2011 (clinicaltrials.gov id NCT00869661) Assuming the definition of SOC immediately changes to ifn/rbv/ns3-pi the day either tv or bc get fda approval, trying to enroll in the Roche/Pharmasset phase III for r7128 would be a good shot. Otherwise the best bet for a late 2010/2011 departure is likely to ntz(alinia)/ifn/rbv/ns3pi with a SAMe chaser.
Some may be prepared to wait for R7128 approval before txing, but that seems a ways out. The frustrating part of this, IMHO opinion, is that our proprietary/competitive model of drug-development works very well when it's an issue of A or B as per the current Schering/Vertex fight, but works poorly when the optimal strategy is A and B, something that would require more cooperation than competition.
For example, though it's been obvious for years that polymerase/protease combos are the way to go, we had to wait until abstract 263 above to have this tested in human. Even then, the combo tests only get done after one company has managed to acquire both types of PI, as Vertex recently did. Meanwhile, the evident first choice from a patient's perspective, R7128 with tv or bc, doesn't get tested.
Also interesting in willing link. Table 3 is the final results for 28 weeks is 82%. So it looks like shorter tx ALSO works here and has a better SVR rate.
It seems some of the protease inhibitors are more effective on genotypes 1 and 2 than they are on 3. The Polymerase inhibitors, however seem to be very potent across all genotypes. R7228 by Pharmasset is one that in interim results showed 90% RVR for genotype 2 and 3 non responders It's also one of two inhibitors being used in the Inform-1 trial WITHOUT interferon. They will be reporting the interim results of this on Saturday. The pre-announcement sounds very promising as inform-1 is adding 2 more co-horts with higher dosages since the lowest dosage results are very good. This REALLY could be the treatment of the future as many other inhibitors, including Pharmasset's 7851 which is 15-20% MORE powerful than 7228 are also effective across all genotypes.
I have no problem with completing the full course of treatments..., it's the doctors and these darn studies that keep me from staying the course. I actually did 52 weeks on one of my treatments w/o clearing, got close at the end, but was finally stopped. I was on 1600 mg of Riba and daily Infergen and was willing to keep going, on another treatment, as well as Procrit and Neupogen, but was stopped at 8 mon. after not clearing. I would do whatever treatment, including the Riba and Interferon, if it had a good chance of clearing me of this stubborn virus.
Susan400
Susan400
by the way they are doing a presentation on debio at EASl this week.
I thought of you when writing Trinity. When Vertex combines the twin PI's this year they may see a huge log drop; could be more than enough to trump the resistant virii. May hit em so fast that there's no time to mutate. On the other hand a few stragglers in scar tissue may make this a pipe dream. The deal with this type treatment is they may drop or reduce riba or IFN and thus open up a type of TX that many people can do.
Current TX may be less effective if you are IR, or cannot complete a longer course of TX of either interferon or ribaviren.
best,
willy
I thought of you when writing Trinity. When Vertex combines the twin PI's this year they may see a huge log drop; could be more than enough to trump the resistant virii. May hit em so fast that there's no time to mutate. On the other hand a few stragglers in scar tissue may make this a pipe dream. The deal with this type treatment is they may drop or reduce riba or IFN and thus open up a type of TX that many people can do.
Current TX may be less effective if you are IR, or cannot complete a longer course of TX of either interferon or ribaviren.
best,
willy
Given the opportunity, I will take the Boceprevir over the Telaprevir any day as I had the horrible rash with Telaprevir. I've had anemia before with all my other treatments using standard SOC drugs and it's totally something that you can work with. That rash that I had was ridiculous and it's not something that I can ever deal with again! I still say that the first doctor that I can convince to give me a try on the Boceprevir after it's available, then I'll be doing it. I really don't care if there's a problem with resistance, but from what a very knowledgeable Hepatologist told me, since I was only on the 2 drugs w/o the Riba in the mix and only on it for 5 weeks and because it will have been over 2 yrs by the time I'm able to get my hands on it, that the resistance may not even be a factor after all and that it's worth a try at it again w/the 3 drugs. It's not like I'm going to be running around affecting other people, donating blood or anything of that nature, so what do I care if I get resistance contained in my own body? Maybe I'm just having some wishful thinking....
Susan400
Susan400
Thanks for the links. There are quite a few presentations as well as one on Schering's 2nd generation drug I believe. The Boceprevir data isn't cutting edge; I think they released this earlier but as preliminary data. They now have solid data and a bit more discussion. For me the anemia is an issue but it is one which can be addressed with epo.
-----------------
"Anemia was seen in about half of patients taking boceprevir, and in a third of patients taking only Pegintron and ribavirin
-----------------------
Regarding the best ever results; it's good news, very good news. The question may remain how many people were on rescue drugs in the trial (if any). If they had trial participants on rescue drugs this may be about as good as it gets. If none were on, then one would surmise that the SVR rates could climb.
Comparing it to Telaprevir...... the same question remains what kind of ultimate SVR rate they can tweak out of the compound. Given that so far they have not used rescue drugs or a 4 week SOC *lead in* we should see the potential for improvement in that compound as well. The 2 compounds should not be compared until we have an apples to "apples" comparison. According to Vertex they are still seeing fewer drop outs, higher compliance and therfore higher success rates.
----------------------
Trinity, no one truly knows the answer to that question and won't until it is proven on large numbers of people. As it sits now they have non-human studies which show that in petrie dishes there is a resistance issue; no question about that I think.
We often then surmise that people are saddled with the resistance forever and I acknowledge that could be true........ but......
Some virologists theorize that after time the PI resistant mutations could revert back to the wild type that SOC can effect, so after time the resistant population could diminish and possibly be overcome with a new attack. How long it takes to revert back is an open question.
2) Somewhat in the same manner that hardy resistant microbes can be beaten with a stronger antibiotic the same principle could apply to defeating a new "resistant" strain. ie;
a) A more powerful PI such as the 2nd generation Scherring compound (reputed to be 15X more powerful than telaprevir in vitro) could possibly wipe it out. or....
b) The new Telaprevir twin PI treatment coming soon which utilized a combination of polymerase and protease inhibitors (telaprevir and VCH-222) the first trial to be at about year end.
c) and other different or more powerful treatments could trump the resistance issue. (adding alinia, predosing lead ins, adding other adjunct compounds)
d) any other means which makes the IFN treatment more effective, possibly such as treating IR if it were an issue
It's all theory and as of yet unproven (on live people and in any numbers) to the best of my knowledge.
best,
Willy
-----------------
"Anemia was seen in about half of patients taking boceprevir, and in a third of patients taking only Pegintron and ribavirin
-----------------------
Regarding the best ever results; it's good news, very good news. The question may remain how many people were on rescue drugs in the trial (if any). If they had trial participants on rescue drugs this may be about as good as it gets. If none were on, then one would surmise that the SVR rates could climb.
Comparing it to Telaprevir...... the same question remains what kind of ultimate SVR rate they can tweak out of the compound. Given that so far they have not used rescue drugs or a 4 week SOC *lead in* we should see the potential for improvement in that compound as well. The 2 compounds should not be compared until we have an apples to "apples" comparison. According to Vertex they are still seeing fewer drop outs, higher compliance and therfore higher success rates.
----------------------
Trinity, no one truly knows the answer to that question and won't until it is proven on large numbers of people. As it sits now they have non-human studies which show that in petrie dishes there is a resistance issue; no question about that I think.
We often then surmise that people are saddled with the resistance forever and I acknowledge that could be true........ but......
Some virologists theorize that after time the PI resistant mutations could revert back to the wild type that SOC can effect, so after time the resistant population could diminish and possibly be overcome with a new attack. How long it takes to revert back is an open question.
2) Somewhat in the same manner that hardy resistant microbes can be beaten with a stronger antibiotic the same principle could apply to defeating a new "resistant" strain. ie;
a) A more powerful PI such as the 2nd generation Scherring compound (reputed to be 15X more powerful than telaprevir in vitro) could possibly wipe it out. or....
b) The new Telaprevir twin PI treatment coming soon which utilized a combination of polymerase and protease inhibitors (telaprevir and VCH-222) the first trial to be at about year end.
c) and other different or more powerful treatments could trump the resistance issue. (adding alinia, predosing lead ins, adding other adjunct compounds)
d) any other means which makes the IFN treatment more effective, possibly such as treating IR if it were an issue
It's all theory and as of yet unproven (on live people and in any numbers) to the best of my knowledge.
best,
Willy
Question: Can those who do not SVR on the protease inhibitors treat again or does the body develop a resistance or whatever the term is called. Has it been proven that additional treatments with the protease inhibitors would be ineffective because of this?
doesn't look like any ntz/alinia news will be released but there's a couple of promising tv presentations, including final prove3 data
http://www.kenes.com/easl2009/Orals/261.htm
and indications that, somewhat surprisingly, there may be a difference in g2/g3 tv response:
http://www.kenes.com/easl2009/Orals/177.htm
Also, FINALLY, results in human that combine polymerase/protease inhibitors (Roche's r7128/itm-191)
http://www.kenes.com/easl2009/Orals/263.htm
Anadys also reports on this, but still in glassware
http://www.kenes.com/easl2009/Orals/213.htm
http://www.kenes.com/easl2009/Orals/261.htm
and indications that, somewhat surprisingly, there may be a difference in g2/g3 tv response:
http://www.kenes.com/easl2009/Orals/177.htm
Also, FINALLY, results in human that combine polymerase/protease inhibitors (Roche's r7128/itm-191)
http://www.kenes.com/easl2009/Orals/263.htm
Anadys also reports on this, but still in glassware
http://www.kenes.com/easl2009/Orals/213.htm
Funny...............Geoffrey Porges, a biotech analyst for Sanford Bernstein who is attending the Copenhagen meeting, said the need to take EPO to control anemia will hurt boceprevir.
"It would be very unusual for a drug to go forward and more or less require the use of another drug that's not even approved for that indication," Porges said.
-----------------------------------------------
Gotta love these analyst, maybe they should come here to learn EPO is common with the drug Ribavirin with just SOC. I''ve had the same problem with anemia under both SOC and boceprevir, no better no worse.
cando
"It would be very unusual for a drug to go forward and more or less require the use of another drug that's not even approved for that indication," Porges said.
-----------------------------------------------
Gotta love these analyst, maybe they should come here to learn EPO is common with the drug Ribavirin with just SOC. I''ve had the same problem with anemia under both SOC and boceprevir, no better no worse.
cando
thanks for the posting Willy; it's spring, dogwoods are in bloom, and it's time for a fresh crop of EASL abstracts. Here's the abstract for that press-relase
http://www.kenes.com/easl2009/Orals/12.htm
Looks like the final sprint1 numbers came in better than expected. Hope Can-do, GB and other blue-pill sprinters find a big smile in the '94%' in the 5th row of that table. Merck stockholders aren't going to be the only disappointed ones if the FDA stalls bc because of the anemia ( personally I'd definitely opt for low HGB over a rash)
http://www.kenes.com/easl2009/Orals/12.htm
Looks like the final sprint1 numbers came in better than expected. Hope Can-do, GB and other blue-pill sprinters find a big smile in the '94%' in the 5th row of that table. Merck stockholders aren't going to be the only disappointed ones if the FDA stalls bc because of the anemia ( personally I'd definitely opt for low HGB over a rash)
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