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73% SVR for Prior Relapsers and 41% SVR for Prior Non-Responders per New Interim Telaprevir Data
This was posted previously but thought a different heading might cause more attention to the very encouraging Telaprevir results just released for both prior relapsers, prior non-responders.
Of note is that prior relapsers show a 73% SVR rate on 12 weeks of Telaprevir plus combo plus 12 weeks combo (24 weeks total treatment). And that 41% of previous non-responders also achieved SVR, a group that some were concerned would not be able to reach SVR because of previous non-response. These are intent-to-treat numbers so per protocol numbers would be higher. Drop out rates were 7% in the Telaprevir group and 4% in the control group without Telaprevir. This seems less than in previous Telaprevir trials and I'm guessing it's because of the shorter exposure (12 weeks) to Telaprevir. Apparently more than 12 weeks of Telaprevir gives no additional benefit.
Interim Analysis Results
PROVE 3 is a randomized, double-blind, placebo-controlled Phase 2b study that enrolled patients who failed prior treatment with peg-IFN and RBV. Patients enrolled in PROVE 3 included prior non-responders (including null responders), prior relapsers and prior breakthroughs to peg-IFN and RBV treatment. The interim analysis included 453 patients that were enrolled and received at least one dose of study drug. In the interim analysis, 52% (60 of 115) of patients randomized to receive a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) achieved undetectable HCV RNA (<10 IU/mL; Roche TaqMan) 12 weeks post-treatment (SVR12). Of the 115 patients, 66 were categorized as non-responders to prior treatment (defined as patients who never achieved undetectable HCV RNA during prior treatment, including null responders), 40 were prior relapsers (defined as patients who had undetectable HCV RNA at the completion of prior treatment, but relapsed during follow-up), and 9 were prior breakthroughs (defined as patients who had viral rebound during prior treatment). Among patients receiving the 24-week telaprevir-based regimen, 41% (27 of 66) of the prior non-responders, 73% (29 of 40) of prior relapsers, and 44% (4 of 9) of prior breakthroughs achieved SVR 12.
“Patients who have not achieved a sustained virologic response with one or more courses of prior interferon-based therapy represent a significant unmet medical need. These patients have few or no available treatment options and they are at increased risk for progressive liver disease,” said John McHutchison, M.D., Principal Investigator for the PROVE 3 Study and Associate Director of Duke Clinical Research Institute.
A summary of available on-treatment and post-treatment antiviral data from the 24-week telaprevir-based regimen is presented below:
Undetectable HCV-RNA by Response to Prior Peg-IFN/RBV Treatment (PROVE 3 24-week regimen; 12 weeks telaprevir+peg-IFN+RBV, followed by 12 weeks peg-IFN+RBV);intent-to-treat analysis
Week 12 Week 24 (end of treatment) SVR 12 (week 36; 12 weeks post-treatment)
Non-responders (n=66) 71% 65% 41%
Relapsers (n=40) 88% 83% 73%
Breakthroughs (n=9) 44% 44% 44%
Total (n=115) 75% 70% 52%
http://news.moneycentral.msn.com/ticker/article.aspx?Feed=BW&Date=20080609&ID=8746457&Symbol=VRTX
Of note is that prior relapsers show a 73% SVR rate on 12 weeks of Telaprevir plus combo plus 12 weeks combo (24 weeks total treatment). And that 41% of previous non-responders also achieved SVR, a group that some were concerned would not be able to reach SVR because of previous non-response. These are intent-to-treat numbers so per protocol numbers would be higher. Drop out rates were 7% in the Telaprevir group and 4% in the control group without Telaprevir. This seems less than in previous Telaprevir trials and I'm guessing it's because of the shorter exposure (12 weeks) to Telaprevir. Apparently more than 12 weeks of Telaprevir gives no additional benefit.
Interim Analysis Results
PROVE 3 is a randomized, double-blind, placebo-controlled Phase 2b study that enrolled patients who failed prior treatment with peg-IFN and RBV. Patients enrolled in PROVE 3 included prior non-responders (including null responders), prior relapsers and prior breakthroughs to peg-IFN and RBV treatment. The interim analysis included 453 patients that were enrolled and received at least one dose of study drug. In the interim analysis, 52% (60 of 115) of patients randomized to receive a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) achieved undetectable HCV RNA (<10 IU/mL; Roche TaqMan) 12 weeks post-treatment (SVR12). Of the 115 patients, 66 were categorized as non-responders to prior treatment (defined as patients who never achieved undetectable HCV RNA during prior treatment, including null responders), 40 were prior relapsers (defined as patients who had undetectable HCV RNA at the completion of prior treatment, but relapsed during follow-up), and 9 were prior breakthroughs (defined as patients who had viral rebound during prior treatment). Among patients receiving the 24-week telaprevir-based regimen, 41% (27 of 66) of the prior non-responders, 73% (29 of 40) of prior relapsers, and 44% (4 of 9) of prior breakthroughs achieved SVR 12.
“Patients who have not achieved a sustained virologic response with one or more courses of prior interferon-based therapy represent a significant unmet medical need. These patients have few or no available treatment options and they are at increased risk for progressive liver disease,” said John McHutchison, M.D., Principal Investigator for the PROVE 3 Study and Associate Director of Duke Clinical Research Institute.
A summary of available on-treatment and post-treatment antiviral data from the 24-week telaprevir-based regimen is presented below:
Undetectable HCV-RNA by Response to Prior Peg-IFN/RBV Treatment (PROVE 3 24-week regimen; 12 weeks telaprevir+peg-IFN+RBV, followed by 12 weeks peg-IFN+RBV);intent-to-treat analysis
Week 12 Week 24 (end of treatment) SVR 12 (week 36; 12 weeks post-treatment)
Non-responders (n=66) 71% 65% 41%
Relapsers (n=40) 88% 83% 73%
Breakthroughs (n=9) 44% 44% 44%
Total (n=115) 75% 70% 52%
http://news.moneycentral.msn.com/ticker/article.aspx?Feed=BW&Date=20080609&ID=8746457&Symbol=VRTX
Eric,
Holy ****, you said you were going for your 12 blood work. I'm so freakin sorry to hear you have relapsed. I'm kind of stunned actually. Sort of puts the 52% of success with Telaprevir in a broader context. Like a "it's still only 50%" context. I'm sure you could agree with someone wanting to take the chance...up till now, all my docs have been blabbin away about less than 10% chances. But if and when I try, I will always keep you in mind...keep me grounded.
I remember the first time I found out I had rebounded....I thought I was so cool...it took months for me to really get upset. Don't know why. Hope you got someone to hold your hand for a while.
Willow
Holy ****, you said you were going for your 12 blood work. I'm so freakin sorry to hear you have relapsed. I'm kind of stunned actually. Sort of puts the 52% of success with Telaprevir in a broader context. Like a "it's still only 50%" context. I'm sure you could agree with someone wanting to take the chance...up till now, all my docs have been blabbin away about less than 10% chances. But if and when I try, I will always keep you in mind...keep me grounded.
I remember the first time I found out I had rebounded....I thought I was so cool...it took months for me to really get upset. Don't know why. Hope you got someone to hold your hand for a while.
Willow
jim - thanks for the post
ca,willy:
I believe that a number of the resistance mutations to either telaprevir or boceprevir confer cross resistance. Both drugs target the active site of the ns3 serine protease in similar ways. See for example:
http://www.ncbi.nlm.nih.gov/pubmed/18201776
however none of these mutations should have any effect on drugs that target other hcv proteins (eg r1626 or r7128)
interesting question about infecting others with resistant strains. We know the resistant strains are less fit and presumably are overwhelmed by fitter but drug-sensitive strains once the selective pressure of the drugs stops. However whether this effect is complete or partial is not clear. Schering and Vertex clearly know the answer from the sequence data they've collected from patients (do your dominant strains, those that would be passed via blood-based infection, exhibit resistance mutations post-relapse?) but I don't know whether they've released these results.
Overall this seems to be very good news with respect to the (lack of) fitness of the resistance mutations - ie they're such wimps that even the low-level anti-viral effect of non-responders is sufficient to knock them out of the ballpark about half the time.
Resistance to NS3 PIs is so common that resistant variants presumably show up in near everyone. The good news seems to be that even the flawed ifn response raised by known relapsers and non-responders (yeah, I know, we're a sorry bunch) is enough to do a decent job of mopping up.
ca,willy:
I believe that a number of the resistance mutations to either telaprevir or boceprevir confer cross resistance. Both drugs target the active site of the ns3 serine protease in similar ways. See for example:
http://www.ncbi.nlm.nih.gov/pubmed/18201776
however none of these mutations should have any effect on drugs that target other hcv proteins (eg r1626 or r7128)
interesting question about infecting others with resistant strains. We know the resistant strains are less fit and presumably are overwhelmed by fitter but drug-sensitive strains once the selective pressure of the drugs stops. However whether this effect is complete or partial is not clear. Schering and Vertex clearly know the answer from the sequence data they've collected from patients (do your dominant strains, those that would be passed via blood-based infection, exhibit resistance mutations post-relapse?) but I don't know whether they've released these results.
Overall this seems to be very good news with respect to the (lack of) fitness of the resistance mutations - ie they're such wimps that even the low-level anti-viral effect of non-responders is sufficient to knock them out of the ballpark about half the time.
Resistance to NS3 PIs is so common that resistant variants presumably show up in near everyone. The good news seems to be that even the flawed ifn response raised by known relapsers and non-responders (yeah, I know, we're a sorry bunch) is enough to do a decent job of mopping up.
Vertex Unveils More Upbeat Hep C Drug Data
06/09/08 - 10:28 AM EDT
An experimental hepatitis C drug from Vertex Pharmaceuticals (VRTX - Cramer's Take - Stockpickr) can knock back the virus even in the most difficult-to-treat patients, according to results from a clinical trial announced Monday.
The news sent Vertex shares up 63 cents, or 2%, to $32.87 in recent trading Monday morning.
The Vertex drug, telaprevir, was able to reduce levels of the hepatitis C virus down to undetectable levels in 52% of so called non-responder or relapse patients. These are patients considered the hardest to treat because they either did not respond to current drugs like interferon and ribavirin, or their virus returned after treatment.
Based on previous studies, roughly 10% of treatment-resistant hepatitis C patients who are then retreated with interferon and ribavirin are successfully cured of their disease.
The new data on telaprevir come from the PROVE 3 study, a phase II clinical trial that enrolled 453 hepatitis C patients who failed to respond to prior treatment. This is an interim analysis, which means that, to date, telaprevir patients have only been followed for 12 weeks post-treatment. A hepatitis C patient is not considered "cured" of the disease until they have undetectable viral levels 24 weeks, or six months, after treatment.
A Race for Market Share
Based on these results, Vertex and partner Johnson & Johnson (JNJ - Cramer's Take - Stockpickr) said Monday that they will start a pivotal phase III study in treatment-failure patients during the third quarter. There has been great market speculation whether Vertex might be able to seek regulatory approval for telaprevir based on PROVE 3 data alone, however.
John Alam, Vertex's chief medical officer, says it is still too early to comment on the company's ultimate plans for telaprevir in treatment-failure patients. The company intends on sharing final data from PROVE 3 with the U.S. Food and Drug Administration by the end of the year or early 2009. In the meantime, Vertex and Johnson & Johnson are moving ahead on finalizing the design for the phase III study of telaprevir in treatment-failure patients, Alam said.
If telaprevir is found to be effective for these hardest-to-treat hepatitis C patients, the commercial potential for Vertex is significant. There are an estimated 250,000 to 300,000 hepatitis C patients in the U.S. who have failed current interferon-ribavirin therapy and are waiting for something new and more effective to be approved so they can be retreated, and hopefully cured.
This is one of the major reasons why the race to develop and market a new hepatitis C drug is so frenzied. Vertex and J&J are facing off with companies like Schering-Plough (SGP - Cramer's Take - Stockpickr), InterMune (ITMN - Cramer's Take - Stockpickr), Roche and Pharmasset (VRUS - Cramer's Take - Stockpickr) -- all of which are hoping that their respective hepatitis C drugs are superior or can be approved first to be the go-to drug for treatment-resistant patients.
A phase III study of telaprevir in hepatitis C patients not previously treated is underway, with data expected in the first half of 2010. If positive, Vertex plans to seek regulatory approval in the second half of 2010.
PROVE 3 Data Breakdown
Breaking down the PROVE 3 interim results further, 41% of telaprevir-treated patients who had previously not responded at all to standard treatment (non-responders) reached undetectable levels of viral load at 12 weeks post treatment. For those patients who did respond to standard treatment but then relapsed during follow-up, treatment with telaprevir led to an undetectable viral load rate of 73% after 12 weeks of follow-up.
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Patients were treated with 12 weeks of telaprevir plus interferon and ribavirin, followed by another 12 weeks of interferon and ribavirin alone.
There is a control arm in the PROVE 3 study, but these patients are still being followed. At this point, 8% of these patients retreated with standard therapy (interferon and ribavirin) had undetectable levels of virus after 12 weeks of treatment. After 36 weeks of treatment, the undetectable level rose to 30%.
While the control arm patients appear to be doing better with longer re-treatment, Vertex's Alam says most of these difficult-to-treat patients must reach undetectable levels by week 12 if they have any real chance for a long-term cure. Most of the patients who reach undetectable levels after 12 weeks of treatment ultimately relapse again, he says.
----------------------------------------------------------------
We'll have to wait until the final numbers are shown. My guess the differences between the SVR's will be far greater than are apparent in the interim results. We don't yet know about the relapse rate on the triple therapy Prove 3's but it was very low in the naives.
There are issues with resistance but I'm not sure that we yet know the extent of the problem. For me....... it looks as if we have a treatment which will shorten TX time by half, that could approach nearly doubling the SVR rate, and which could potentially quadruple the cure rate for past treatment failures. I hope that we can all celebrate those wonderful advances. This drug will save lives; lots of them.
Willy
06/09/08 - 10:28 AM EDT
An experimental hepatitis C drug from Vertex Pharmaceuticals (VRTX - Cramer's Take - Stockpickr) can knock back the virus even in the most difficult-to-treat patients, according to results from a clinical trial announced Monday.
The news sent Vertex shares up 63 cents, or 2%, to $32.87 in recent trading Monday morning.
The Vertex drug, telaprevir, was able to reduce levels of the hepatitis C virus down to undetectable levels in 52% of so called non-responder or relapse patients. These are patients considered the hardest to treat because they either did not respond to current drugs like interferon and ribavirin, or their virus returned after treatment.
Based on previous studies, roughly 10% of treatment-resistant hepatitis C patients who are then retreated with interferon and ribavirin are successfully cured of their disease.
The new data on telaprevir come from the PROVE 3 study, a phase II clinical trial that enrolled 453 hepatitis C patients who failed to respond to prior treatment. This is an interim analysis, which means that, to date, telaprevir patients have only been followed for 12 weeks post-treatment. A hepatitis C patient is not considered "cured" of the disease until they have undetectable viral levels 24 weeks, or six months, after treatment.
A Race for Market Share
Based on these results, Vertex and partner Johnson & Johnson (JNJ - Cramer's Take - Stockpickr) said Monday that they will start a pivotal phase III study in treatment-failure patients during the third quarter. There has been great market speculation whether Vertex might be able to seek regulatory approval for telaprevir based on PROVE 3 data alone, however.
John Alam, Vertex's chief medical officer, says it is still too early to comment on the company's ultimate plans for telaprevir in treatment-failure patients. The company intends on sharing final data from PROVE 3 with the U.S. Food and Drug Administration by the end of the year or early 2009. In the meantime, Vertex and Johnson & Johnson are moving ahead on finalizing the design for the phase III study of telaprevir in treatment-failure patients, Alam said.
If telaprevir is found to be effective for these hardest-to-treat hepatitis C patients, the commercial potential for Vertex is significant. There are an estimated 250,000 to 300,000 hepatitis C patients in the U.S. who have failed current interferon-ribavirin therapy and are waiting for something new and more effective to be approved so they can be retreated, and hopefully cured.
This is one of the major reasons why the race to develop and market a new hepatitis C drug is so frenzied. Vertex and J&J are facing off with companies like Schering-Plough (SGP - Cramer's Take - Stockpickr), InterMune (ITMN - Cramer's Take - Stockpickr), Roche and Pharmasset (VRUS - Cramer's Take - Stockpickr) -- all of which are hoping that their respective hepatitis C drugs are superior or can be approved first to be the go-to drug for treatment-resistant patients.
A phase III study of telaprevir in hepatitis C patients not previously treated is underway, with data expected in the first half of 2010. If positive, Vertex plans to seek regulatory approval in the second half of 2010.
PROVE 3 Data Breakdown
Breaking down the PROVE 3 interim results further, 41% of telaprevir-treated patients who had previously not responded at all to standard treatment (non-responders) reached undetectable levels of viral load at 12 weeks post treatment. For those patients who did respond to standard treatment but then relapsed during follow-up, treatment with telaprevir led to an undetectable viral load rate of 73% after 12 weeks of follow-up.
Previous «
1 2 3
» Next
Patients were treated with 12 weeks of telaprevir plus interferon and ribavirin, followed by another 12 weeks of interferon and ribavirin alone.
There is a control arm in the PROVE 3 study, but these patients are still being followed. At this point, 8% of these patients retreated with standard therapy (interferon and ribavirin) had undetectable levels of virus after 12 weeks of treatment. After 36 weeks of treatment, the undetectable level rose to 30%.
While the control arm patients appear to be doing better with longer re-treatment, Vertex's Alam says most of these difficult-to-treat patients must reach undetectable levels by week 12 if they have any real chance for a long-term cure. Most of the patients who reach undetectable levels after 12 weeks of treatment ultimately relapse again, he says.
----------------------------------------------------------------
We'll have to wait until the final numbers are shown. My guess the differences between the SVR's will be far greater than are apparent in the interim results. We don't yet know about the relapse rate on the triple therapy Prove 3's but it was very low in the naives.
There are issues with resistance but I'm not sure that we yet know the extent of the problem. For me....... it looks as if we have a treatment which will shorten TX time by half, that could approach nearly doubling the SVR rate, and which could potentially quadruple the cure rate for past treatment failures. I hope that we can all celebrate those wonderful advances. This drug will save lives; lots of them.
Willy
Oh - I also was in the 24 + 24 arm. No results were published for that arm since I am one of the first participants to be at the 12 week post treatment date. I am hopeful that the response rate in the arm I was in will be better that the 12 + 12 arm.
Eric
Eric
I think Vertex will use these results to try and bypass the phase 3 trial and go for NDA in the restrictive case of prior failures. I hope they succeed. Interesting that they did not show the correlation to RVR.
I am a relapser by the way.
Eric
I am a relapser by the way.
Eric
Thanks for that Jim. The future is looking brighter and brighter. Mike
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