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Telaprevir 107 study (past TX failures)
This will get ample discussion at AASLD. Telaprevir can cure past NULL RESPONDERS- How do you like that? Willy
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Vertex Pharmaceuticals Incorporated
Interim Results from Study 107 Highlight the Potential Role of Telaprevir-Based Regimens in HCV Patients Who Failed Prior Treatment
* 57% of prior treatment null responder patients achieved an SVR with a 48-week telaprevir-based regimen
* 90% of prior treatment relapsers and 55% of prior treatment partial responders achieved an SVR with 24-week or 48-week telaprevir-based regimens
* Results provide further support for the ongoing Phase 3 registration study, REALIZE, in treatment-failure patients
CAMBRIDGE, Mass., Oct 28, 2009 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that treatment with telaprevir-based regimens in Study 107 resulted in high sustained viral response (SVR) rates in treatment-failure patients infected with hepatitis C virus (HCV). Interim results from 94 patients in Study 107 showed that 90% of prior treatment relapsers (n=29) and 55% of prior treatment partial responders (n=29) achieved an SVR after treatment with 24-week or 48-week telaprevir-based regimens, and 57% of prior treatment null responders (n=28) achieved an SVR after treatment with a 48-week telaprevir-based regimen. At the time of this interim analysis, eight patients (7%, n=117) had discontinued all therapy due to adverse events, which included 4 patients who discontinued due to rash and 1 patient who discontinued due to anemia.
Study 107 is an ongoing, open-label Phase 2 rollover study of patients who had received pegylated interferon (peg-IFN) and ribavirin (RBV) in the control arms of the Phase 2 PROVE studies and who did not achieve an SVR. Telaprevir is an investigational HCV protease inhibitor being developed by Vertex Pharmaceuticals in collaboration with Tibotec and Mitsubishi Tanabe Pharma.
"Results that include SVR rates of 57% in the difficult-to-treat null responder population are important for prior treatment-failure patients who have limited treatment options," said Peter Mueller, Ph.D., Vertex's Executive Vice President, Global Research and Development and Chief Scientific Officer. "These results, as well as data from other telaprevir studies, continue to support the potential role of telaprevir as a new treatment option for hepatitis C patients."
Patient Type TVR regimen SVR Viral Relapse Rates
Prior Null Responders* T12 + PR 48 (n=28) 57% (16/28) 20% (4/20)
Prior Partial Responders** T12 + PR24 (n=25) 55% (16/29) 22% (5/23)
orT12 + PR48 (n=3)
or Unassigned (n=1)
Prior Relapsers+ T12 + PR24 (n= 25) or 90% (26/29) 4% (1/28)
T12 + PR48 (n=3) or
Unassigned (n=1)
Prior Viral Breakthrough± T12 + PR24 (n=7) or 75% (6/8) 0 (0/6)
T12 + PR48 (n=1)
* Defined as patients who achieved a viral load decline of less than 1 log10 at week 4 or 2 log10 or less at week 12 during prior therapy
**Defined as patients who had a greater than 2 log10 viral decline at week 12 but had detectable HCV RNA at week 24
+Defined as patients who had undetectable HCV RNA at the end of treatment with peg-IFN and RBV but subsequently relapsed
±Defined as patients who had undetectable HCV RNA but relapsed before the end of treatment
Undetectable HCV RNA is defined as <25IU/mL undetectable by Roche COBAS Taqman HCV test
This analysis includes 1 prior partial responder and 1 prior relapser who discontinued all treatment prior to reaching week 12 of dosing and subsequently achieved an SVR - designated as "unassigned"
Interim Analysis of Study 107
Discontinuation of all therapy due to adverse events occurred in eight patients. A complete safety analysis is still being performed and will be reported when the full data are presented at a medical conference expected in 2010.
"These results, which suggest that 48-week telaprevir-based regimens may help to optimize outcomes for treatment-failure patients, support the rationale for many of the key design elements of the ongoing Phase 3 trial, REALIZE, being conducted by our partner, Tibotec," said Dr. Robert Kauffman, Vertex's Senior Vice President, Clinical Development and Chief Medical Officer. "In Study 107 we observed patterns of response across the treatment-failure population, and made amendments during the course of the study in an effort to optimize treatment. The SVR rates reported here are part of our effort to identify the most appropriate regimen for this difficult-to-treat population and to show that 48-week regimens may further enhance SVR rates for certain treatment-failure patients."
Study 107 Design and Interim Results
Study 107 is an ongoing, open-label Phase 2 rollover study of telaprevir in combination with peg-IFN and RBV in patients who had previously enrolled in the control arms of either of the PROVE 1, PROVE 2 or PROVE 3 studies, and did not achieve an SVR. Patients in Study 107 were well-characterized as null responders, partial responders, relapsers or breakthroughs, based on their antiviral response to prior peg-IFN and RBV treatment as a result of their participation in the control arms of prior PROVE clinical trials. This interim analysis, which includes all but two patients who are still on treatment in the study, was conducted to support planned regulatory agency interactions in Europe. Final analysis from Study 107 is planned for presentation at a medical conference in 2010.
The interim results reported here reflect data from patients who were considered to have received an appropriate treatment regimen based on their prior response to peg-IFN and RBV and reflecting the amendments made during the conduct of Study 107. When Study 107 began, all patients were to receive 12 weeks of telaprevir in combination with peg-IFN and RBV followed by an additional 12 weeks of peg-IFN and RBV (T12/PR24). Stopping rules required any patient who did not achieve undetectable HCV RNA by week 4 to stop all treatment. In 2008, Study 107 was amended and underwent several changes. The most important change to the protocol was to the week 4 stopping rules for virologic failure, as it became evident that treatment-failure patients had a somewhat slower viral response to treatment than did naïve patients. Following this amendment, patients who had detectable HCV RNA at week 4 were permitted to continue therapy. Additionally, while the initial study protocol specified 24 weeks of total treatment for all patients, a longer total duration of treatment (48 weeks) was determined to be warranted in prior null responders to provide a higher likelihood of achieving an SVR.
From a total of 117 patients who enrolled in Study 107, data from 94 patients were included in this interim analysis. The 23 patients not included in this interim analysis were null responders, who, prior to protocol amendments, were designated to receive only 24 weeks of therapy, and a portion of whom met the strict stopping rule criteria at week 4. The 48-week telaprevir-based regimen is being studied in the ongoing Phase 3 trial, known as REALIZE, in treatment-failure patients. Final data will be presented at a medical conference in 2010.
------------------------------------------------------------------------------------------------------------------------------
Vertex Pharmaceuticals Incorporated
Interim Results from Study 107 Highlight the Potential Role of Telaprevir-Based Regimens in HCV Patients Who Failed Prior Treatment
* 57% of prior treatment null responder patients achieved an SVR with a 48-week telaprevir-based regimen
* 90% of prior treatment relapsers and 55% of prior treatment partial responders achieved an SVR with 24-week or 48-week telaprevir-based regimens
* Results provide further support for the ongoing Phase 3 registration study, REALIZE, in treatment-failure patients
CAMBRIDGE, Mass., Oct 28, 2009 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that treatment with telaprevir-based regimens in Study 107 resulted in high sustained viral response (SVR) rates in treatment-failure patients infected with hepatitis C virus (HCV). Interim results from 94 patients in Study 107 showed that 90% of prior treatment relapsers (n=29) and 55% of prior treatment partial responders (n=29) achieved an SVR after treatment with 24-week or 48-week telaprevir-based regimens, and 57% of prior treatment null responders (n=28) achieved an SVR after treatment with a 48-week telaprevir-based regimen. At the time of this interim analysis, eight patients (7%, n=117) had discontinued all therapy due to adverse events, which included 4 patients who discontinued due to rash and 1 patient who discontinued due to anemia.
Study 107 is an ongoing, open-label Phase 2 rollover study of patients who had received pegylated interferon (peg-IFN) and ribavirin (RBV) in the control arms of the Phase 2 PROVE studies and who did not achieve an SVR. Telaprevir is an investigational HCV protease inhibitor being developed by Vertex Pharmaceuticals in collaboration with Tibotec and Mitsubishi Tanabe Pharma.
"Results that include SVR rates of 57% in the difficult-to-treat null responder population are important for prior treatment-failure patients who have limited treatment options," said Peter Mueller, Ph.D., Vertex's Executive Vice President, Global Research and Development and Chief Scientific Officer. "These results, as well as data from other telaprevir studies, continue to support the potential role of telaprevir as a new treatment option for hepatitis C patients."
Patient Type TVR regimen SVR Viral Relapse Rates
Prior Null Responders* T12 + PR 48 (n=28) 57% (16/28) 20% (4/20)
Prior Partial Responders** T12 + PR24 (n=25) 55% (16/29) 22% (5/23)
orT12 + PR48 (n=3)
or Unassigned (n=1)
Prior Relapsers+ T12 + PR24 (n= 25) or 90% (26/29) 4% (1/28)
T12 + PR48 (n=3) or
Unassigned (n=1)
Prior Viral Breakthrough± T12 + PR24 (n=7) or 75% (6/8) 0 (0/6)
T12 + PR48 (n=1)
* Defined as patients who achieved a viral load decline of less than 1 log10 at week 4 or 2 log10 or less at week 12 during prior therapy
**Defined as patients who had a greater than 2 log10 viral decline at week 12 but had detectable HCV RNA at week 24
+Defined as patients who had undetectable HCV RNA at the end of treatment with peg-IFN and RBV but subsequently relapsed
±Defined as patients who had undetectable HCV RNA but relapsed before the end of treatment
Undetectable HCV RNA is defined as <25IU/mL undetectable by Roche COBAS Taqman HCV test
This analysis includes 1 prior partial responder and 1 prior relapser who discontinued all treatment prior to reaching week 12 of dosing and subsequently achieved an SVR - designated as "unassigned"
Interim Analysis of Study 107
Discontinuation of all therapy due to adverse events occurred in eight patients. A complete safety analysis is still being performed and will be reported when the full data are presented at a medical conference expected in 2010.
"These results, which suggest that 48-week telaprevir-based regimens may help to optimize outcomes for treatment-failure patients, support the rationale for many of the key design elements of the ongoing Phase 3 trial, REALIZE, being conducted by our partner, Tibotec," said Dr. Robert Kauffman, Vertex's Senior Vice President, Clinical Development and Chief Medical Officer. "In Study 107 we observed patterns of response across the treatment-failure population, and made amendments during the course of the study in an effort to optimize treatment. The SVR rates reported here are part of our effort to identify the most appropriate regimen for this difficult-to-treat population and to show that 48-week regimens may further enhance SVR rates for certain treatment-failure patients."
Study 107 Design and Interim Results
Study 107 is an ongoing, open-label Phase 2 rollover study of telaprevir in combination with peg-IFN and RBV in patients who had previously enrolled in the control arms of either of the PROVE 1, PROVE 2 or PROVE 3 studies, and did not achieve an SVR. Patients in Study 107 were well-characterized as null responders, partial responders, relapsers or breakthroughs, based on their antiviral response to prior peg-IFN and RBV treatment as a result of their participation in the control arms of prior PROVE clinical trials. This interim analysis, which includes all but two patients who are still on treatment in the study, was conducted to support planned regulatory agency interactions in Europe. Final analysis from Study 107 is planned for presentation at a medical conference in 2010.
The interim results reported here reflect data from patients who were considered to have received an appropriate treatment regimen based on their prior response to peg-IFN and RBV and reflecting the amendments made during the conduct of Study 107. When Study 107 began, all patients were to receive 12 weeks of telaprevir in combination with peg-IFN and RBV followed by an additional 12 weeks of peg-IFN and RBV (T12/PR24). Stopping rules required any patient who did not achieve undetectable HCV RNA by week 4 to stop all treatment. In 2008, Study 107 was amended and underwent several changes. The most important change to the protocol was to the week 4 stopping rules for virologic failure, as it became evident that treatment-failure patients had a somewhat slower viral response to treatment than did naïve patients. Following this amendment, patients who had detectable HCV RNA at week 4 were permitted to continue therapy. Additionally, while the initial study protocol specified 24 weeks of total treatment for all patients, a longer total duration of treatment (48 weeks) was determined to be warranted in prior null responders to provide a higher likelihood of achieving an SVR.
From a total of 117 patients who enrolled in Study 107, data from 94 patients were included in this interim analysis. The 23 patients not included in this interim analysis were null responders, who, prior to protocol amendments, were designated to receive only 24 weeks of therapy, and a portion of whom met the strict stopping rule criteria at week 4. The 48-week telaprevir-based regimen is being studied in the ongoing Phase 3 trial, known as REALIZE, in treatment-failure patients. Final data will be presented at a medical conference in 2010.
I believe the current Telprevir trial discouraged the use of rescue drugs and helpers, like AD's, just so they could get cleaner data. The addition of those helpers would also mean less of a dropout rate due to adverse reactions.
http://www.reuters.com/article/marketsNews/idCNN2727066420091028?rpc=44
A few snippets, view the link for the complete article. -Willy
___________________________________________________
Interim results from an ongoing study, released on Wednesday, showed 57 percent of patients who failed to respond to the standard treatments of pegylated-interferon and ribavirin, and 90 percent of those who responded but later relapsed, achieved a sustained viral response when telaprevir was added to their regimen.
The percentage of patients in whom the virus is undetectable after completing treatment yields the critical measure known as sustained viral response, or SVR.
"Ninety percent in prior relapsers is very impressive and suggests that the rate in naive (previously untreated) patients could move up to the 75-80 percent range," said Sanford Bernstein analyst Geoffrey Porges."
______________________________
also.....
Of 117 patients enrolled in the study, data from 94 was included in the interim analysis, Vertex said.
Eight patients in the study discontinued treatment due to adverse side effects, including rash and anemia.
"The most impressive finding in this analysis is the low discontinuation rate due to adverse events," Porges said. "The discontinuation rate of 7 percent and the rash rate of 3.5 percent are materially lower than the rates in the earlier blinded studies with telaprevir and pegylated-interferon."
________________________________________
(my comment-Willy)
I think we may see future higher SVR rates in the Vertex trials, that would be the automatic result of reducing the drop out rate. We may also see that with rescue drugs or the use of a 4 week lead in rates could also improve some.
We are just beginning to see some of the great new treatments, not just Telaprevir or Boceprevir. We are also just beginning to enter the period where these will be combined (such as with polymerase and protease inhibitors).
Good things are coming (particularly for geno 1's) if we can wait.
best,
Willy
A few snippets, view the link for the complete article. -Willy
___________________________________________________
Interim results from an ongoing study, released on Wednesday, showed 57 percent of patients who failed to respond to the standard treatments of pegylated-interferon and ribavirin, and 90 percent of those who responded but later relapsed, achieved a sustained viral response when telaprevir was added to their regimen.
The percentage of patients in whom the virus is undetectable after completing treatment yields the critical measure known as sustained viral response, or SVR.
"Ninety percent in prior relapsers is very impressive and suggests that the rate in naive (previously untreated) patients could move up to the 75-80 percent range," said Sanford Bernstein analyst Geoffrey Porges."
______________________________
also.....
Of 117 patients enrolled in the study, data from 94 was included in the interim analysis, Vertex said.
Eight patients in the study discontinued treatment due to adverse side effects, including rash and anemia.
"The most impressive finding in this analysis is the low discontinuation rate due to adverse events," Porges said. "The discontinuation rate of 7 percent and the rash rate of 3.5 percent are materially lower than the rates in the earlier blinded studies with telaprevir and pegylated-interferon."
________________________________________
(my comment-Willy)
I think we may see future higher SVR rates in the Vertex trials, that would be the automatic result of reducing the drop out rate. We may also see that with rescue drugs or the use of a 4 week lead in rates could also improve some.
We are just beginning to see some of the great new treatments, not just Telaprevir or Boceprevir. We are also just beginning to enter the period where these will be combined (such as with polymerase and protease inhibitors).
Good things are coming (particularly for geno 1's) if we can wait.
best,
Willy
The general trend is the thing to pay attention to. The study is small; made up of SOC Prove 1 and 2 TX failures. This provided the clear data about exactly how they failed while on SOC. Based on that they were able to note responses and determine a course of triple therapy TX for the nonreponders in the Phase 3 trials.
The actual percentages would likely change in a much larger study.
BTW....all Phase 3 TVR dosing ended a month or two ago. They won't share data for a while but they probably know a lot at this point.
Off to work.
Willy
The actual percentages would likely change in a much larger study.
BTW....all Phase 3 TVR dosing ended a month or two ago. They won't share data for a while but they probably know a lot at this point.
Off to work.
Willy
Interesting. I would like to see better data on the partial responders - success rate 12/24 vs 12/48. Also, what was the RVR rate and how did that affect SVR. But this is encouraging news, since I am in the realize trial and am about to do shot 38.
Yes.
TVR works best on geno 1's and 2's
The geno 4 study was small and only so-so if I recall, and the geno 3 trial was a huge disappointment. TVR did very little to response/ SVR rate.
In the USA there are a large number of genotype 1's.
For many non or null responders there has not been a decent viable TX option. One also wonders what would happen with a 4 week SOC lead in. It is possible that these numbers could be improved some. To the best of my knowledge this was also done without rescue drugs; another possible means of improvement.
best,
Willy
TVR works best on geno 1's and 2's
The geno 4 study was small and only so-so if I recall, and the geno 3 trial was a huge disappointment. TVR did very little to response/ SVR rate.
In the USA there are a large number of genotype 1's.
For many non or null responders there has not been a decent viable TX option. One also wonders what would happen with a 4 week SOC lead in. It is possible that these numbers could be improved some. To the best of my knowledge this was also done without rescue drugs; another possible means of improvement.
best,
Willy
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