Aa
vertex for tx failures and relapsers.
Vertex Pharmaceuticals to Start Phase 3 'REALIZE' Trial with Telaprevir in Treatment-Failure HCV Patients
First HCV protease inhibitor in pivotal trial for this difficult
to treat patient population
Trial to enroll all major treatment-failure patient groups,
including null responders, partial responders and relapsers
Two telaprevir registration programs to address significant unmet
need in treatment-naive and treatment-failure patients
CAMBRIDGE, Mass., Aug 19, 2008 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the Company has reached agreement with U.S. and E.U. regulatory authorities to proceed with the REALIZE trial, a pivotal Phase 3 clinical trial with the hepatitis C virus (HCV) protease inhibitor telaprevir in combination therapy for patients with chronic HCV infection who failed to achieve a sustained viral response (SVR) with prior therapy. The trial will be conducted in the U.S. and E.U. and will enroll approximately 650 genotype 1 HCV patients who failed prior treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV). The trial is designed to evaluate two 48-week telaprevir-based regimens in comparison with a 48-week control arm. Telaprevir will be dosed for 12 weeks. The primary endpoint of the trial is SVR, defined as undetectable HCV RNA (less than10 IU/mL) 24 weeks after the completion of treatment.
"In Phase 2 clinical trials, telaprevir-based regimens have demonstrated the potential to increase sustained viral response rates across a broad spectrum of patients infected with the hepatitis C virus, including patients who failed to achieve SVR with previous pegylated interferon and ribavirin therapy, many of whom are at high risk for life-threatening HCV-related complications," said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, Weill Medical College of Cornell University. "The REALIZE trial of telaprevir is a landmark Phase 3 trial of an investigational HCV protease inhibitor in null responder and other patients who failed prior treatment and will seek to generate additional data to demonstrate the benefit of telaprevir in this difficult to treat patient population."
"Approximately 6 million patients are chronically infected with hepatitis C in the U.S. and E.U. today, and approximately 650,000 of these patients have failed previous treatments of pegylated interferon and ribavirin therapy and are in need of a new therapeutic option to treat their disease," said Kurt C. Graves, Vertex's Executive Vice President, Chief Commercial Officer and Head, Strategic Development. "Data generated from this Phase 3 trial in treatment-failure patients, as well as data from the ongoing Phase 3 ADVANCE trial in treatment-naive patients, may further contribute to the emerging profile of telaprevir to address the significant medical need in both treatment-naive and treatment-failure patients."
Global Phase 3 Trial in Patients who Failed to Achieve SVR with Prior Therapy
The REALIZE Trial (Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes) will enroll approximately 650 genotype 1 HCV patients and will be conducted by Tibotec at more than 100 centers in the U.S. and E.U. Tibotec expects to complete enrollment of the REALIZE trial in the first quarter of 2009. The trial will include the following patient groups:
- Null responders (defined as patients who achieved less than 2 log
reduction in HCV RNA at Week 12 of prior therapy);
- Partial responders (defined as patients who achieved at least a 2
log reduction at Week 12, but failed to achieve undetectable HCV RNA
by Week 24 of prior therapy); and
- Relapsers (defined as patients who had undetectable HCV RNA at the
completion of at least 42 weeks of prior treatment, but relapsed
during follow-up).
The REALIZE trial will dose telaprevir in combination with pegylated
interferon alfa-2a (PEGASYS) and ribavirin. The REALIZE trial will
enroll three 48-week trial arms:
1. Telaprevir dosed at 750 mg every eight hours (q8h) for 12
weeks in combination with standard doses of peg-IFN and RBV,
followed by 36 weeks of treatment with peg-IFN and RBV
alone;
2. Delayed start arm, comprised of 4 weeks of treatment with
peg-IFN and RBV, followed by telaprevir dosed at 750 mg q8h
for 12 weeks in combination with standard doses of peg-IFN
and RBV, followed by another 32 weeks of peg-IFN and RBV
alone; and
3. A control arm with standard doses of peg-IFN and RBV dosed
for 48 weeks
Patients in all treatment arms will be followed for 24 weeks after completion of treatment to assess SVR.
Updates on the status of Vertex and Tibotec's clinical trials of telaprevir are available at www.clinicaltrials.gov.
First HCV protease inhibitor in pivotal trial for this difficult
to treat patient population
Trial to enroll all major treatment-failure patient groups,
including null responders, partial responders and relapsers
Two telaprevir registration programs to address significant unmet
need in treatment-naive and treatment-failure patients
CAMBRIDGE, Mass., Aug 19, 2008 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the Company has reached agreement with U.S. and E.U. regulatory authorities to proceed with the REALIZE trial, a pivotal Phase 3 clinical trial with the hepatitis C virus (HCV) protease inhibitor telaprevir in combination therapy for patients with chronic HCV infection who failed to achieve a sustained viral response (SVR) with prior therapy. The trial will be conducted in the U.S. and E.U. and will enroll approximately 650 genotype 1 HCV patients who failed prior treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV). The trial is designed to evaluate two 48-week telaprevir-based regimens in comparison with a 48-week control arm. Telaprevir will be dosed for 12 weeks. The primary endpoint of the trial is SVR, defined as undetectable HCV RNA (less than10 IU/mL) 24 weeks after the completion of treatment.
"In Phase 2 clinical trials, telaprevir-based regimens have demonstrated the potential to increase sustained viral response rates across a broad spectrum of patients infected with the hepatitis C virus, including patients who failed to achieve SVR with previous pegylated interferon and ribavirin therapy, many of whom are at high risk for life-threatening HCV-related complications," said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, Weill Medical College of Cornell University. "The REALIZE trial of telaprevir is a landmark Phase 3 trial of an investigational HCV protease inhibitor in null responder and other patients who failed prior treatment and will seek to generate additional data to demonstrate the benefit of telaprevir in this difficult to treat patient population."
"Approximately 6 million patients are chronically infected with hepatitis C in the U.S. and E.U. today, and approximately 650,000 of these patients have failed previous treatments of pegylated interferon and ribavirin therapy and are in need of a new therapeutic option to treat their disease," said Kurt C. Graves, Vertex's Executive Vice President, Chief Commercial Officer and Head, Strategic Development. "Data generated from this Phase 3 trial in treatment-failure patients, as well as data from the ongoing Phase 3 ADVANCE trial in treatment-naive patients, may further contribute to the emerging profile of telaprevir to address the significant medical need in both treatment-naive and treatment-failure patients."
Global Phase 3 Trial in Patients who Failed to Achieve SVR with Prior Therapy
The REALIZE Trial (Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes) will enroll approximately 650 genotype 1 HCV patients and will be conducted by Tibotec at more than 100 centers in the U.S. and E.U. Tibotec expects to complete enrollment of the REALIZE trial in the first quarter of 2009. The trial will include the following patient groups:
- Null responders (defined as patients who achieved less than 2 log
reduction in HCV RNA at Week 12 of prior therapy);
- Partial responders (defined as patients who achieved at least a 2
log reduction at Week 12, but failed to achieve undetectable HCV RNA
by Week 24 of prior therapy); and
- Relapsers (defined as patients who had undetectable HCV RNA at the
completion of at least 42 weeks of prior treatment, but relapsed
during follow-up).
The REALIZE trial will dose telaprevir in combination with pegylated
interferon alfa-2a (PEGASYS) and ribavirin. The REALIZE trial will
enroll three 48-week trial arms:
1. Telaprevir dosed at 750 mg every eight hours (q8h) for 12
weeks in combination with standard doses of peg-IFN and RBV,
followed by 36 weeks of treatment with peg-IFN and RBV
alone;
2. Delayed start arm, comprised of 4 weeks of treatment with
peg-IFN and RBV, followed by telaprevir dosed at 750 mg q8h
for 12 weeks in combination with standard doses of peg-IFN
and RBV, followed by another 32 weeks of peg-IFN and RBV
alone; and
3. A control arm with standard doses of peg-IFN and RBV dosed
for 48 weeks
Patients in all treatment arms will be followed for 24 weeks after completion of treatment to assess SVR.
Updates on the status of Vertex and Tibotec's clinical trials of telaprevir are available at www.clinicaltrials.gov.
I think the reason for limited and carefully timed usage of the protease inhibitors is due to the fact they HCV can develop resistence to the drugs in a matter of weeks.
What is concerning me about Vertex though - is that we are introducing an additional drug to the mix, which who knows what long term side effects, which for many people, perhaps even most, will not add any real benefit (as many can succeed on SOC with only 2 drugs). We are only starting to understand SOC now, and it will be a while before Vertex, and the other drugs in development are understood. That's why I am thinking we may see a protocol arise whereby perhaps, a patient tries SOC, and if at 4 weeks not RVR, then Vertex is introduced (either immediately, or after a 1 month break or so). I mean, for a 1A who would be RVR and eligible for short treatment anyway, what is the benefit?
Vertex is an exciting option for those who have not responded, but I am very concerned that already people are not treating because they are terrified. Adding a Rash to the mix of the already present symptoms isn't necessarily going to get the masses who have already decided treatment would be too tough, running to the doctor to give it a go, even if it does cut treatment time.
Hopefully something better is in the pipeline that can make the existing treatments less invasive symptom wise, or if more effective than current, at least doesn't add additional side effect miseries to the mix.
Vertex is an exciting option for those who have not responded, but I am very concerned that already people are not treating because they are terrified. Adding a Rash to the mix of the already present symptoms isn't necessarily going to get the masses who have already decided treatment would be too tough, running to the doctor to give it a go, even if it does cut treatment time.
Hopefully something better is in the pipeline that can make the existing treatments less invasive symptom wise, or if more effective than current, at least doesn't add additional side effect miseries to the mix.
Is this trial listed on ClinicalTrials.org yet? I couldn't find it. If not, does anyone know when or if the locations are posted?
A few things;
I think that some of this is a little confusing since it seems that trials mentioned are getting confused; the earlier non responders trials done by both Vertex and Sherring Plough or the current trials in progress.
Drug companies try to put the best "face" on their trials or trial results and it's our job or the job of the press to sort it out for us. Unfortunately the results are often fed to us in various forms which don't always invite easy comparisons.
Were I to treat, I would take the treatment which offered the highest SVR rate and the shortest treatment time. Right now that would appear to be Vertex without regard to whether one was treatment naive or a past treatment failure. Some will allege that the treatment is less safe or harder than SOC and they are correct incrementally since the stats show that there are more discontinuations but in the balance they have shown to have a far higher SVR rate which could climb to nearly double that of SOC. If one was a treatment failure one might have 3-4 times the success rate with Vertex than of simply retrying SOC.
When one makes assessments about "safety" one must also factor in the results of long term use of current SOC. There are many people who have suffered a range of all the black box warnings with appear on the label of the current meds one must take. Oddly.....sometimes one even reads threads from people who attained an SVR and yet wish that they had never treated due to sides that have lingered long enough that the people consider them permanent. IF one could reduce the exposure to current SOC might one reduce the various forms of damage which SOC can cause?
I'm a 55 year old male genotype 1. With SOC my chances of SVR may at best be 50-50. When one looks about this forum one often sees people who have failed various forms of TX many times. Should one factor in the amount of drugs one takes repeated times when one fails repeatedly....or is forced to extend ones treatment as some people also must do? This is one of the difficult choices that one must make when deciding whether to treat or to wait.
I don't personally find that Vertex response rates will serve to keep people from treating. I do understand that they may choose to wait for a better form of treatment. Vertex is only just entering the Phase 3 trials. I don't think people have yet seen all that the compound can do. Vertex has been developed expressly to raise the SVR rate and to shorten treatment. I've never heard it suggested by anyone that it will ONLY be offered to past treatment failures. Why would that be done when it seems to work well for all groups of people with HCV? It is still to early to make announcements about the success rates since Vertex has not released final results on the Prove 3 treatment failure trial .......but..... the preliminary results are great. They still have yet the Phase 3 trial to tweak the efficacy and results. How could this be improved further?
1) Improved management of sides (like the rash),
2) use of rescue drugs (such as procrit for low RBC),
3) and investigating the use of a SOC lead in which may yet improve further the response rate.
They already have an unprecedented success rate; well beyond good enough for FDA approval. They will raise the bar further in Phase 3 and surpass past results, IMHO.
Boceprevir is a second, it may be a close second or may not be as close as the press may think. As mentioned the 2 trials may not be easily compared due to many differences. Restated.... it may be UNwise to compare them until more data is revealed. I think that the efficacy may not be as great as Vertex. With Boceprevir, one saw lackluster success rates with past treatment failures, a higher relapse rate and overall a longer TX time when compared to Vertex. It is still too early to tell definitively but that is just my opinion based on what I've read.
I'm excited that both of these are making it though trials. There will soon be two protease inhibitors which may be combined with a polymerase inhibitor in the very near future. Success in this area could bring the SVR rate higher still and treatment time to a even shorter period. One of the Vertex arms in the naive trial has a 8 week triple therapy course of treatment. IF people respond well in that trial we may see a comparable response rate as the "12 & 12" but it could further sidestep rash and anemia issues for many participants. I'm content to wait...... for the results of the trial..... and for now..... for a better form of treatment.
I don't think that we will have that long to wait.
best,
willy
I think that some of this is a little confusing since it seems that trials mentioned are getting confused; the earlier non responders trials done by both Vertex and Sherring Plough or the current trials in progress.
Drug companies try to put the best "face" on their trials or trial results and it's our job or the job of the press to sort it out for us. Unfortunately the results are often fed to us in various forms which don't always invite easy comparisons.
Were I to treat, I would take the treatment which offered the highest SVR rate and the shortest treatment time. Right now that would appear to be Vertex without regard to whether one was treatment naive or a past treatment failure. Some will allege that the treatment is less safe or harder than SOC and they are correct incrementally since the stats show that there are more discontinuations but in the balance they have shown to have a far higher SVR rate which could climb to nearly double that of SOC. If one was a treatment failure one might have 3-4 times the success rate with Vertex than of simply retrying SOC.
When one makes assessments about "safety" one must also factor in the results of long term use of current SOC. There are many people who have suffered a range of all the black box warnings with appear on the label of the current meds one must take. Oddly.....sometimes one even reads threads from people who attained an SVR and yet wish that they had never treated due to sides that have lingered long enough that the people consider them permanent. IF one could reduce the exposure to current SOC might one reduce the various forms of damage which SOC can cause?
I'm a 55 year old male genotype 1. With SOC my chances of SVR may at best be 50-50. When one looks about this forum one often sees people who have failed various forms of TX many times. Should one factor in the amount of drugs one takes repeated times when one fails repeatedly....or is forced to extend ones treatment as some people also must do? This is one of the difficult choices that one must make when deciding whether to treat or to wait.
I don't personally find that Vertex response rates will serve to keep people from treating. I do understand that they may choose to wait for a better form of treatment. Vertex is only just entering the Phase 3 trials. I don't think people have yet seen all that the compound can do. Vertex has been developed expressly to raise the SVR rate and to shorten treatment. I've never heard it suggested by anyone that it will ONLY be offered to past treatment failures. Why would that be done when it seems to work well for all groups of people with HCV? It is still to early to make announcements about the success rates since Vertex has not released final results on the Prove 3 treatment failure trial .......but..... the preliminary results are great. They still have yet the Phase 3 trial to tweak the efficacy and results. How could this be improved further?
1) Improved management of sides (like the rash),
2) use of rescue drugs (such as procrit for low RBC),
3) and investigating the use of a SOC lead in which may yet improve further the response rate.
They already have an unprecedented success rate; well beyond good enough for FDA approval. They will raise the bar further in Phase 3 and surpass past results, IMHO.
Boceprevir is a second, it may be a close second or may not be as close as the press may think. As mentioned the 2 trials may not be easily compared due to many differences. Restated.... it may be UNwise to compare them until more data is revealed. I think that the efficacy may not be as great as Vertex. With Boceprevir, one saw lackluster success rates with past treatment failures, a higher relapse rate and overall a longer TX time when compared to Vertex. It is still too early to tell definitively but that is just my opinion based on what I've read.
I'm excited that both of these are making it though trials. There will soon be two protease inhibitors which may be combined with a polymerase inhibitor in the very near future. Success in this area could bring the SVR rate higher still and treatment time to a even shorter period. One of the Vertex arms in the naive trial has a 8 week triple therapy course of treatment. IF people respond well in that trial we may see a comparable response rate as the "12 & 12" but it could further sidestep rash and anemia issues for many participants. I'm content to wait...... for the results of the trial..... and for now..... for a better form of treatment.
I don't think that we will have that long to wait.
best,
willy
im new to the protese drugs...i thought they were injectable ..sorry bout that..ive herad that BOC has very little,if any rash sx...are schling plow a buch of liars or what?
The Phase 3 trial for 1 HCV patients who are RVR, is hardly inspiring. I mean, isn't 24 weeks often all that is needed with SOC for RVR now?
If they could combine such treatments with perhaps say, a monthly dose of interferon instead of a weekly one, that would excite me. But as it stands, adding a third drug with additional side effects to the mix, I fear is just going to scare more people away from starting treatment. There already are too many people scared IMO.
If they could combine such treatments with perhaps say, a monthly dose of interferon instead of a weekly one, that would excite me. But as it stands, adding a third drug with additional side effects to the mix, I fear is just going to scare more people away from starting treatment. There already are too many people scared IMO.
Here is the next paragraph from the above article (the Vertex Press Release)
http://www.hivandhepatitis.com/hep_c/news/2008/082208_a.html
"Pivotal Trial in Treatment-Naive Patients
Vertex and Tibotec are also conducting the global 3-arm pivotal Phase 3 ADVANCE trial in treatment-naive genotype 1 HCV patients that is focused on 24-week telaprevir-based regimens for patients achieving rapid viral response (HCV RNA less than 10 IU/mL at 4 weeks). Vertex is on track to complete enrollment of the ADVANCE trial during the fourth quarter of 2008 and expects to have sustained viral response (SVR) data from the trial in the first half of 2010."
http://www.hivandhepatitis.com/hep_c/news/2008/082208_a.html
"Pivotal Trial in Treatment-Naive Patients
Vertex and Tibotec are also conducting the global 3-arm pivotal Phase 3 ADVANCE trial in treatment-naive genotype 1 HCV patients that is focused on 24-week telaprevir-based regimens for patients achieving rapid viral response (HCV RNA less than 10 IU/mL at 4 weeks). Vertex is on track to complete enrollment of the ADVANCE trial during the fourth quarter of 2008 and expects to have sustained viral response (SVR) data from the trial in the first half of 2010."
Boceprevir was all over the news about a week ago. seems this is not the first time shering-plough has fudged trial results to make a drug look better. There also were posts about it on this forum within the last 2 weeks.
I have not seen this news on Boceprevir so any link would be appreciated. I doubt that the data would be skewed due to rescue drugs, but I had some bad feelings about them myself when they showed the control are at only 38% SVR -- much lower than anything I have seen. I thought it made the BOC results look too high.
frijole
frijole
i have been talking to my hepatologist about the Telaprevir trials and he told me none of the Vertex trials will allow rescue drugs. I think Vertex does not want to skew the trial results. Boceprevir has been in the news lately about their trial data being misleading. Maybe some of this is due to them allowing rescue drugs?
That is also one of my questions, as i needed neupogen during SOC. I just found out about this last night; it was announced 8/19. I'm sure more info will be coming. When I saw my hepatologist last week, he said that a relapser trial is coming, but he thought it would happen mid 2009.
Rocker.. I'm not sure what you mean. The shots are still the same as soc (weekly peg shots). It's unfortunate that they feel the need to have a control arm for relapsers and nonresponders.. I also had hoped that for a 24 week trial. Anyway, it's nice to see things moving along for those of us who did not reach SVR.
Rocker.. I'm not sure what you mean. The shots are still the same as soc (weekly peg shots). It's unfortunate that they feel the need to have a control arm for relapsers and nonresponders.. I also had hoped that for a 24 week trial. Anyway, it's nice to see things moving along for those of us who did not reach SVR.
I find the statement about Vertex being fouced on those who have failed Hep C treatments quite informing. It is what I have suspected for a while, when Vertex is approved, in may not become SOC. It may instead be an add-on, for those who have failed SOC.
Anyone who has decided not to try SOC now, because they are waiting for Vertex, may be making a mistake, as they may be required to try SOC first anyway (better to do 2 drugs, than 3).
Anyone who has decided not to try SOC now, because they are waiting for Vertex, may be making a mistake, as they may be required to try SOC first anyway (better to do 2 drugs, than 3).
WHere did you get the info on the rescue drugs. I know this has been the protocol, but this late in trials, I thought the general consensus( or may it was just that I was hoping) was to get a comparison of Boceprevir (which uses rescue drugs in trials) and Telaprevir.
I got this same email from Vertex ( you can get on their email alerts thru their website for anyone who is interested) and forwarded it to the trial coordinator in Dallas who said she hadn't heard anything yet.
frijole
I got this same email from Vertex ( you can get on their email alerts thru their website for anyone who is interested) and forwarded it to the trial coordinator in Dallas who said she hadn't heard anything yet.
frijole
Rock: you will know if you are getting the study drug when you get the worse rash of your life :-) seriously if you can get a VL test on your own after 2 weeks and your are unde then you most like got the study drug. some say the Telaprevir pill tastes bitter but Vertex may have got hip to this and now make the placebo bitter as well.
CoWriter: No rescue drugs in the Vertex trials
CoWriter: No rescue drugs in the Vertex trials
If i shoot 3 times a day....i will know what group im in????....can i tell which group i will be in.???...proberly a dumb question
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