Aa
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
About miked I dont think he ever reached SVR so he was probebly more of a partial responder then a breaktrougher.
ca
ca
I just spoke to one of the principle investigators on this trial and he said that their non-responder arm had no idea if there were any participants who had no 2 log drop previously. He alluded to the fact that these people (never had a 2 log drop) are extremely resistant to Inf and it is doubtful that adding just telaprevir will be the answer for the vast majority of them. BIG BUMMER.
I am in the Prove 3 trial. I'm a previous non-resonder (partial responder who did not have a 2 log drop by 12 weeks the last time I treated) getting ready for my 12 week post labs, This news has me a little nervous. I'm grateful that I was in the 48 week arm and I did not have any breakthrough once I cleared. I was <30 at week 4 and UD at week 8. I go for my next labs on June 16.
While not wishing to rain on this parade, as a previous breakthrough I am not finding this news so great for me. At 44% SVR12 rate that is comparable to the non-responders rate of 41%. It is a very small sample of prior breakthroughs(9 people) though, so perhaps this figure will not turn out to be representative.
I had somehow believed that prior breakthroughs would be easier to treat than people who did not get any interferon response but that might not be the case at all. I think I based that belief on miked from this forum who did Prove3 and got SVR with the triple tx and had been a prior breakthrough. Anyway with odds of 44% I wouldn't be stepping up to the plate for the telaprevir triple if I could help it (ignoring the fact that I already have telaprevir resistant variants anyway).
dointime
I had somehow believed that prior breakthroughs would be easier to treat than people who did not get any interferon response but that might not be the case at all. I think I based that belief on miked from this forum who did Prove3 and got SVR with the triple tx and had been a prior breakthrough. Anyway with odds of 44% I wouldn't be stepping up to the plate for the telaprevir triple if I could help it (ignoring the fact that I already have telaprevir resistant variants anyway).
dointime
ty for the link!
An increasing number of new hepatitis C virus NS3-protease inhibitors are being evaluated for the treatment of chronic hepatitis C. Treatment-induced selection of mutants conferring resistance to protease inhibitors has been shown both in vivo and in vitro. A specific mutation, A156T has been shown to confer high-level resistance to several such agents (BILN2061, VX-950, SCH446211 (SCH6) and SCH503034). Here we report the presence of the A156T mutation in close to 1% of NS3 sequences within the liver quasispecies of a chronic hepatitis C patient never treated with anti-NS3-protease inhibitors.
PMID: 18006035 [PubMed - indexed for MEDLINE]
But if i understand it right it says that Hcv infected people who never had been in contact,
with protease inhibitors still have up to 1% of the A156T mutation how many % dose thos have who have been in contact with the meds that targeting NS3?
Is NS3 a part of the HCV virus were this A156 mutation dwells?
I must admit this is not the easiest english for me. If someone can explain what the above text means in plain english would be must appreciated.
My point by asking those question about resistance, was an attempt to balance the enthusiasm,that I have so much understanding for being a relapser my self, so we dont rush into something that seems intellegent and vise, but could end up in something dangerous and not so vise. Wouldn´t be the first time that happens when narrowminded
economical aspects is involved would it?
I´ve heard about another new med Debio 025 a cyclofelin inhibitor that has no crosresistance with other hep c meds.
ca
An increasing number of new hepatitis C virus NS3-protease inhibitors are being evaluated for the treatment of chronic hepatitis C. Treatment-induced selection of mutants conferring resistance to protease inhibitors has been shown both in vivo and in vitro. A specific mutation, A156T has been shown to confer high-level resistance to several such agents (BILN2061, VX-950, SCH446211 (SCH6) and SCH503034). Here we report the presence of the A156T mutation in close to 1% of NS3 sequences within the liver quasispecies of a chronic hepatitis C patient never treated with anti-NS3-protease inhibitors.
PMID: 18006035 [PubMed - indexed for MEDLINE]
But if i understand it right it says that Hcv infected people who never had been in contact,
with protease inhibitors still have up to 1% of the A156T mutation how many % dose thos have who have been in contact with the meds that targeting NS3?
Is NS3 a part of the HCV virus were this A156 mutation dwells?
I must admit this is not the easiest english for me. If someone can explain what the above text means in plain english would be must appreciated.
My point by asking those question about resistance, was an attempt to balance the enthusiasm,that I have so much understanding for being a relapser my self, so we dont rush into something that seems intellegent and vise, but could end up in something dangerous and not so vise. Wouldn´t be the first time that happens when narrowminded
economical aspects is involved would it?
I´ve heard about another new med Debio 025 a cyclofelin inhibitor that has no crosresistance with other hep c meds.
ca
Susie: Does this mean that after 12 weeiks of telaprevir + 12 more weeks of SOC, 41% of previous non-responders will still be unetected?
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My take is that the 41% represents SVR 12 (UND at 12 weeks post tx) for previous non-responders and not just those UND. Since the 12 week post tx UND seems to correlate very closely with the 24 week post tx UND, I would think that there's every reason to believe that these figures should hold up to a significant extent.
-- Jim
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My take is that the 41% represents SVR 12 (UND at 12 weeks post tx) for previous non-responders and not just those UND. Since the 12 week post tx UND seems to correlate very closely with the 24 week post tx UND, I would think that there's every reason to believe that these figures should hold up to a significant extent.
-- Jim
Susie: my read is that it's much better than that. Of the 115 in the 12-triple+12-soc arm, 66 were non-responders using a "never achieved undetectable HCV RNA during prior treatment" definition. Of the 66, 27 were still UND 12 weeks after EOT. Some reduction in the svr rate can be expected at the final 24 week test, but as I recall the number of relapses between 12 and 24 runs under 5%. Also, 66 is going to be too few to statistically distinguish "never got 1 log" vs "no 2 log by 12" vs "got 2 log but never got und" but hopefully they'll post the details at some point.
CA: I came across the following
http://www.ncbi.nlm.nih.gov/pubmed/18006035
which seems to provide a definite answer to your question about transmission of resistance strains. The A156T mutation confers resistance to all three NS3-targeted drugs (telaprevir, boceprevir, biln). If up to 1% of virions carry this mutation in a never-treated patient they are definitely fit enough to pass an infection. Given the 1% it might take a transfusion rather than a needle stick.
CA: I came across the following
http://www.ncbi.nlm.nih.gov/pubmed/18006035
which seems to provide a definite answer to your question about transmission of resistance strains. The A156T mutation confers resistance to all three NS3-targeted drugs (telaprevir, boceprevir, biln). If up to 1% of virions carry this mutation in a never-treated patient they are definitely fit enough to pass an infection. Given the 1% it might take a transfusion rather than a needle stick.
I only had a chance to glance at this cause I am due at my doctor's in 30 minutes. Does this mean that after 12 weeiks of telaprevir + 12 more weeks of SOC, 41% of previous non-responders will still be unetected? It will be interesting to see how many hold that SVR at 24 weeks EOT. I hope all of them do. Also, unless I am reading this uncorrectly, it does not say the previous non-responders never had a 2 log drop. I wish we could know that data as it is very important to some of us.
Susie
Susie
Eric,
You thought we weren't paying attention to your test results. I am, but I sure don't want to put any pressure on you about it all....it's all such a **** shoot. Anyway, I apologize to you for my "overreacting"....it's good to be wrong some times!!
Here's crossing my fingers for more good news for you and about Telaprevir in the coming weeks. It's hard to believe that the FDA would approve with just two trials and even harder to believe that by the end of this year we could have the drug available to us all. Like a dream that I'm not sure I want to dream.....so I'll just keep waiting.
Willows
You thought we weren't paying attention to your test results. I am, but I sure don't want to put any pressure on you about it all....it's all such a **** shoot. Anyway, I apologize to you for my "overreacting"....it's good to be wrong some times!!
Here's crossing my fingers for more good news for you and about Telaprevir in the coming weeks. It's hard to believe that the FDA would approve with just two trials and even harder to believe that by the end of this year we could have the drug available to us all. Like a dream that I'm not sure I want to dream.....so I'll just keep waiting.
Willows
Obviously great news... However, I have two friends now with advanced Cirrhosis who are living in constant fear. It's a shame they can't be given the drug without the possible placebo. I have elected not to travel 12 times from Las Vegas to L.A. for my treatment because of the 33% chance I will get a placebo.
Here in Las Vegas gas is today at $4.16 for regular unleaded and my Durango at 13 mpg would be a huge cost and loss if I were to get a placebo, to say nothing of the wear and tear on my body.
Rest assured that I will work tirelessly on Vertex to see if I can guarantee the Teleprevir instead of a placebo in exceptional cases such as myself (4 times non-responder), Susan (another marathon non-responder), and others who have also suffered a lot here through failed treatments. “The wheel that squeaks the loudest, gets the grease” Stay tuned...
Magnum
Here in Las Vegas gas is today at $4.16 for regular unleaded and my Durango at 13 mpg would be a huge cost and loss if I were to get a placebo, to say nothing of the wear and tear on my body.
Rest assured that I will work tirelessly on Vertex to see if I can guarantee the Teleprevir instead of a placebo in exceptional cases such as myself (4 times non-responder), Susan (another marathon non-responder), and others who have also suffered a lot here through failed treatments. “The wheel that squeaks the loudest, gets the grease” Stay tuned...
Magnum
Yay!!
I thought so, but obviously we are all waiting right along with you for these results---you gotta be feeling the love :-)
Izzy
I thought so, but obviously we are all waiting right along with you for these results---you gotta be feeling the love :-)
Izzy
I am sorry to post such a confusing message. I have not relapsed; I was trying to say that I was in the group that had the best chance of SVR and I also treated longer than anyone in the just release data. All good news!
Sorry for the confusion,
Eric
Sorry for the confusion,
Eric
Have been in the roll over study prove 3.
On my way to the week 12 point.
Over 6 log at baseline.
I never developed rash.
Was nauseous only on the first day after treatment started, then half the next day.
Non detected at week 4.
Slight blip at week 8 (<60 Iu/mL)
Have been working out daily since last 2 weeks to try to improve my chances. Something I couldn't do when off treatment because it made me feel horrid.
Happy to get the chance to try this stuff! Happy to hear it is making a difference to so many people!
Cheese.
On my way to the week 12 point.
Over 6 log at baseline.
I never developed rash.
Was nauseous only on the first day after treatment started, then half the next day.
Non detected at week 4.
Slight blip at week 8 (<60 Iu/mL)
Have been working out daily since last 2 weeks to try to improve my chances. Something I couldn't do when off treatment because it made me feel horrid.
Happy to get the chance to try this stuff! Happy to hear it is making a difference to so many people!
Cheese.
I caught that as well-but I am hoping that he meant he was a relapser BEFORE this trial. Surely he didn't get the results already-he just had the blood work today.....
Did I miss something? Did Eric already get his results? Where did you see he relapsed? It just can't be! It isn't on his profile.
Foo
Foo
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.
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
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.
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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
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