Aa
NEW HOPE?
VX-950 is an investigational oral protease inhibitor for the treatment of hepatitis C virus infection. HCV protease is a unique viral enzyme that is essential for viral replication, and for helping the virus evade host immune defenses. VX-950 is one of two drugs in development at Vertex for the treatment of HCV, and is one of the most advanced drug candidates in this new class of direct antivirals. On May 10, 2005, Vertex reported details of interim results from a Phase Ib study of VX-950 in patients with chronic hepatitis C virus infection. In this study, VX-950 was well-tolerated and demonstrated potent antiviral activity. In addition, patients treated with 750 mg of VX-950 every eight hours achieved a median reduction of HCV-RNA of 4.4 log10, equivalent to a 25,000-fold reduction in viral levels, at the end of 14 days of treatment. At the end of 14 days of treatment, 4 of 8 patients in the 750 mg dose group tested HCV-RNA negative in the quantitative Roche COBAS TaqMan
I need to start editing better.....sorry for the redundancy and the typos in my previous post.
I don't believe it has been tested on genotypes other than 1 yet. I imagine that by/in Phase III it will be. I don't understand the differences between genotypes, but here is a crude explanation of what I do know:
The drug was built by a computer, molecule by molecule, in order to get it to "stick" to the virus. That is an issue, since I have heard it described that the "dimple" on the virus is where the drug needs to stick, and it had been tough to do that. The drug inhibits NS3/4 protease which I guess is what hides it from the immune system. The drug has a half life about equal to that of the virus. Once uncoated, the virus is eliminated by the immune system, and thus, cannot replicate. EVR is often a great indicator of SVR, and the greater than 3 log drop in 3 days is an important indicator. Even if interferon (whatever form is used by then) is needed, the number of shots should be dramatically reduced. The person I have talked to there tells me that the worst of the sides are cumulative, as far as neurological issues go.
This is only a guess on my part: Since genotypes 2 and 3 are easier to treat than geno. 1, I would hope that would be the case here, too. The only way to know is to see it in the clinic.
VRTX was just upgraded on Friday by JPM, and their analyst said it was the best of 9 compounds currently being tested. I would hope the FDA does everything they can to keep the timeline moving.
This is just a guess on my part, but I think drug cos. target geno. 1 more because it is the toughest to treat (and most common) and maybe they figure if you could treat the toughest, than the "easier" (I know, nothing's easy) should work as well.
John
The drug was built by a computer, molecule by molecule, in order to get it to "stick" to the virus. That is an issue, since I have heard it described that the "dimple" on the virus is where the drug needs to stick, and it had been tough to do that. The drug inhibits NS3/4 protease which I guess is what hides it from the immune system. The drug has a half life about equal to that of the virus. Once uncoated, the virus is eliminated by the immune system, and thus, cannot replicate. EVR is often a great indicator of SVR, and the greater than 3 log drop in 3 days is an important indicator. Even if interferon (whatever form is used by then) is needed, the number of shots should be dramatically reduced. The person I have talked to there tells me that the worst of the sides are cumulative, as far as neurological issues go.
This is only a guess on my part: Since genotypes 2 and 3 are easier to treat than geno. 1, I would hope that would be the case here, too. The only way to know is to see it in the clinic.
VRTX was just upgraded on Friday by JPM, and their analyst said it was the best of 9 compounds currently being tested. I would hope the FDA does everything they can to keep the timeline moving.
This is just a guess on my part, but I think drug cos. target geno. 1 more because it is the toughest to treat (and most common) and maybe they figure if you could treat the toughest, than the "easier" (I know, nothing's easy) should work as well.
John
This sounds like a great hope. Will it only be effective for genotype 1 or will weaker genotypes such as 3a be treatable with these inhibitors as well?
Go VX-950!, but more "GOOD HOPE" offered by Tarvacin, which on 8-8-05 entered into a human HEP-C Phase1 trial at Bach & Godofsky Infectious Diseases in Bradenton, FL., with Dr. Eliot W. Godofsky as principle investigator.
For more on the Tarvacin HEP-C trial, see this MedHelp thread:
http://www.medhelp.org/perl6/hepatitis/messages/39170.html
For more on the Tarvacin HEP-C trial, see this MedHelp thread:
http://www.medhelp.org/perl6/hepatitis/messages/39170.html
By the way, my name is John. I should have signed the prior post.
I am posting because I know quite a bit about VX-950. I own the stock, basically because of this drug.
First, phase IB was 2 week trial only. There was a greater than 3 log drop of vl in only 3 days. After 11 days in the optimal dose group, half did go below the level of quantitation, with a median drop of 4.4 logs. Current treatment averages about 2.5 logs over 12 weeks. In other words, it reduced viral load by 25,000 times over 11 days, whereas current treatment reduces it on average by 100 times over 12 weeks. This is why leading hepatologists were calling it the single most important presentation at DDW this year.
Phase IB was an oral suspension in water. The pill prototype is made and will be available for phase II. In animal models, the pill form has actually shown even better bioavailibilty, which means, results should actually improve, with maybe smaller dosing. A second phase IB trial is scheduled to begin in Europe in the next couple of months. It will be a 2 week trial but this time with interferon, which in vitro, added a 1-2 log drop vs. VX-950 alone.
There were no adverse events, no cardial toxicity (as with BILN 2061), and side effects will minimal and non-specific-fatigue, etc.
Phase II will begin in the US later this year, and there will be studies for a monotherapy, their other drug MMPD, and with current treatment. The trials will be 1 or 3 months in duration. The fast-acting nature of the drug suggests a much shorter treatment time.
Yes, 4 out of 8 is the same as current treatment. But that does not take into account that that number was reached in only 11 days. This was also in geno 1 type patients.
To this point, no other drug approved or in the clinic has shown anywhere near the activity this drug has. That is why there is so much hope. Vertex designed this drug molecule by molecule using computers to find a way to bind the drug to the virus and uncoat the necessary protease (NS3/4 I think). The half life of the drug is about equal to the half life of the virus, which is a big help.
Here is their gameplan:
Phase IB in Europe in the 4th qtr. IND with FDA in the 4th qtr, with Phase II scheduled to start by the end of the year, the other phase II trials to begin early next year. They will be using a 3 month followup instead of 6 month in phase II because they will be using the most sensitive test, Taqman. Also, if SVR on the sensitive tests is neg. at 3 months, the chance of relapse is just as small as current assumptions and diagnostics.
Phase III should begin in 2007, but this will have a 6 month followup. They plan on filing the NDA by 2008 (hopefully that timeline can be met) and I am sure this qualifies for a priority 6 month review.
This is the best candidate I know of to be used as a monotherapy. Even if interferon is needed, it might only be a few shots instead of 48, and maybe ribavirin won't be necessary, which would eliminate some terrible side effects.
Don't forget, interferon as we know it may not be the best thing available in a few years. Albuferon from Human Genome Sciences is in late phase II testing, and this would only be taken once every 2-4 weeks. I am quite optomisitic that in a few years, the treatment landscape will be quite different.
Also, I have always lurked, but never posted until now. The quality of all of your posts and support is tremendous, that's why I kept coming back to lurk.
and finally, some of VRTX's webcasts are archived at www.vrtx.com if anyone is interested in listening. I have not missed one yet.
First, phase IB was 2 week trial only. There was a greater than 3 log drop of vl in only 3 days. After 11 days in the optimal dose group, half did go below the level of quantitation, with a median drop of 4.4 logs. Current treatment averages about 2.5 logs over 12 weeks. In other words, it reduced viral load by 25,000 times over 11 days, whereas current treatment reduces it on average by 100 times over 12 weeks. This is why leading hepatologists were calling it the single most important presentation at DDW this year.
Phase IB was an oral suspension in water. The pill prototype is made and will be available for phase II. In animal models, the pill form has actually shown even better bioavailibilty, which means, results should actually improve, with maybe smaller dosing. A second phase IB trial is scheduled to begin in Europe in the next couple of months. It will be a 2 week trial but this time with interferon, which in vitro, added a 1-2 log drop vs. VX-950 alone.
There were no adverse events, no cardial toxicity (as with BILN 2061), and side effects will minimal and non-specific-fatigue, etc.
Phase II will begin in the US later this year, and there will be studies for a monotherapy, their other drug MMPD, and with current treatment. The trials will be 1 or 3 months in duration. The fast-acting nature of the drug suggests a much shorter treatment time.
Yes, 4 out of 8 is the same as current treatment. But that does not take into account that that number was reached in only 11 days. This was also in geno 1 type patients.
To this point, no other drug approved or in the clinic has shown anywhere near the activity this drug has. That is why there is so much hope. Vertex designed this drug molecule by molecule using computers to find a way to bind the drug to the virus and uncoat the necessary protease (NS3/4 I think). The half life of the drug is about equal to the half life of the virus, which is a big help.
Here is their gameplan:
Phase IB in Europe in the 4th qtr. IND with FDA in the 4th qtr, with Phase II scheduled to start by the end of the year, the other phase II trials to begin early next year. They will be using a 3 month followup instead of 6 month in phase II because they will be using the most sensitive test, Taqman. Also, if SVR on the sensitive tests is neg. at 3 months, the chance of relapse is just as small as current assumptions and diagnostics.
Phase III should begin in 2007, but this will have a 6 month followup. They plan on filing the NDA by 2008 (hopefully that timeline can be met) and I am sure this qualifies for a priority 6 month review.
This is the best candidate I know of to be used as a monotherapy. Even if interferon is needed, it might only be a few shots instead of 48, and maybe ribavirin won't be necessary, which would eliminate some terrible side effects.
Don't forget, interferon as we know it may not be the best thing available in a few years. Albuferon from Human Genome Sciences is in late phase II testing, and this would only be taken once every 2-4 weeks. I am quite optomisitic that in a few years, the treatment landscape will be quite different.
Also, I have always lurked, but never posted until now. The quality of all of your posts and support is tremendous, that's why I kept coming back to lurk.
and finally, some of VRTX's webcasts are archived at www.vrtx.com if anyone is interested in listening. I have not missed one yet.
I think this drug, even in combination with Interferon, is supposed to have less sx than the current tx.
Susan
Susan
John,
Thank you for your infomative post. There are a lot of folks here, including myself, who are eager for something better to come along. I appreciate you taking the time to post what you know about this new drug. I hope your investment pays off handsomely!
Susan
Thank you for your infomative post. There are a lot of folks here, including myself, who are eager for something better to come along. I appreciate you taking the time to post what you know about this new drug. I hope your investment pays off handsomely!
Susan
Thank you, but I must say, the investment paying off would be icing on the cake, as I, like many in here, are looking for a better treatment option. It is ironic that the disease led me to the investment, when it is usually the other way around.
It seems to me that they are planning this well, as they are ahead of curve going into phase II. I have actually considered getting in a clinical trial if things would fall in place for that.
It seems to me that they are planning this well, as they are ahead of curve going into phase II. I have actually considered getting in a clinical trial if things would fall in place for that.
4 out of 8 were negative, that seems like the same 50% we now have, plus 2 out of the 4 were still positive with a more sensitive test, it seems like less than 50%, but I am no math wiz. I guess the remarkable thing is that there are no shots and it happened in 14 days?
My new GI, Dr. Cecil, has high hopes for this drug and believes it will be available within a couple of years. However, he did say he thinks it will be used in combination with interferon.
Susan
Susan
I have heard that after the initial drop Vertex 950 loses momentum.
It may yet emerge as a drug to be used in combination with interferon.
My own Doctor who is a consultant to a number of drug discovery companies believes that the current generation of inhibitors in clinical trials are more likely to be combination drugs than mono-therapies.
It may yet emerge as a drug to be used in combination with interferon.
My own Doctor who is a consultant to a number of drug discovery companies believes that the current generation of inhibitors in clinical trials are more likely to be combination drugs than mono-therapies.
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