CTON, DO YOU HAVE A LINK TO V-950 W/OUT RIBA

[prettydamscared]

Do you have a link to the (2) vertex-950 studies that you referred to earlier today, the two that didn't use riba and peg.  I can only find info about one study that seems to have concluded in May of 2005 where 28 chronically infected HCV patients were dosed with (3) different amounts of vertex, 450 mgs, 750 and 1250 mcgs respectively.  

If this study concluded in spring of 2005, I don't understand why we're not hearing any svr news regarding this study.

Vertex's press release dated May 17, 2005 regarding this study does say that "at the end of dosing, a total of 5 patients in the Phase Ib study across the dose groups tested HCV-RNA negative in the quantitative Roche COBAS TaqMan‚ assay (<30 IU/mL), reaching this level sometime between day 11 and 14. Following completion of the 14-day dosing period, a slow increase in HCV-RNA levels was observed during a 28-day post-dosing period in these patients. Twenty-eight days after receiving their last dose of VX-950, there were two patients that had viral levels of more than 1 log10 below their pre-treatment levels."

This is the only info I can find on a vx-950 without riba and peg and it doesn't seem that spectacular when you really read it.  When was another done without peg/riba?

Thanks, Char

[couldn't think of a nickname]

The other study without riba was a month before the 12 patient triple combo study. That phase 1b study was 2 weeks of IFN and 950, where they got a 5.5 log reduction in those 2 weeks.
Found at www.vrtx.com.

Cambridge, MA, January 9, 2006– New data announced today by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) show that VX-950, an investigational oral hepatitis C virus (HCV) protease inhibitor, dosed in combination with pegylated interferon alfa-2a (Pegasys‚; peg-IFN), achieved a rapid and dramatic reduction in plasma viral RNA levels in patients with chronic genotype 1 HCV infection. In this Phase Ib study, the combination of VX-950 and peg-IFN produced an initial median reduction in plasma HCV RNA of more than 3 log10 in the first two days, followed by continued decline to a median 5.5 log10 reduction in HCV RNA at day 14, which equates to a 300,000-fold reduction in viral levels. The majority of patients (6 of 8) receiving the combination achieved HCV RNA levels below the limit of quantitation (30 IU/mL, as measured by the Roche TaqMan® assay) at 14 days, with 4 of 8 patients achieving HCV RNA levels below the limit of detection (10 IU/mL, Roche TaqMan®). The antiviral activity of the combination through 14 days was significantly greater than the activity of VX-950 administered as a single agent, and much greater than peg-IFN alone. In addition, VX-950 appeared to be well-tolerated when dosed alone and in combination with peg-IFN in the study. The full data set will be presented at a medical conference later this year.

“These data show that VX-950, in combination with pegylated interferon, produced a very rapid viral response in each of these genotype 1 patients, who are historically the most difficult to treat effectively,” said Henk W. Reesink, MD, Associate Professor of Medicine at Academic Medical Center in Amsterdam, and a lead investigator for the study. “The profound decreases in viral load strongly support the evaluation of VX-950 in combination with pegylated interferon as part of a three-month treatment paradigm to achieve sustained viral responses (SVR) in HCV patients.”

Study Design and Results
The 14-day, randomized, blinded, placebo-controlled Phase Ib study enrolled 20 treatment-naïve patients with genotype 1 HCV, the most prevalent and difficult to treat form of HCV infection. Patients were randomized to receive a new tablet formulation of VX-950 at a dose of 750 mg every eight hours (q8h) in combination with a standard dose of peg-IFN (n=8), the same dose of VX-950 administered alone (n=8), or a standard dose of peg-IFN alone (n=4). The median viral load for all patients at study entry was 6.65 log10 IU/mL HCV RNA (approximately 4.4 million IU/mL). Available interim results indicate:

A median 5.5 log10 reduction in HCV RNA in patients receiving VX-950 and peg-IFN for 14 days; 6 of 8 patients had viral levels below the limit of quantitation (30 IU/mL) at 14 days, and 4 of 8 also achieved viral levels below the limit of detection (10 IU/mL).
A median 4.0 log10 reduction in HCV RNA in patients receiving VX-950 alone for 14 days; 1 of 8 patients had viral levels below the limit of detection (10 IU/mL).
A median 1.0 log10 reduction in HCV RNA in patients receiving peg-IFN alone for 14 days; no patients had viral levels below the limit of quantitation (30 IU/mL) at 14 days.
Safety
A preliminary safety review has been conducted that indicates that the treatment was well tolerated. All patients completed dosing and no serious adverse events were reported. All adverse events in the patients receiving VX-950 alone were reported as mild. Typical interferon-related side effects, of mild to moderate severity, were reported in the patients that received peg-IFN along with VX-950 or placebo. Laboratory-related adverse events of neutropenia in one patient and thrombocytopenia in one patient were reported among the patients who received peg-IFN. Neutropenia and thrombocytopenia have previously been reported in patients receiving peg-IFN alone. It is not known if the two patients in whom these events occurred were also receiving VX-950, because the full safety database has not yet been unblinded. A complete safety analysis will be conducted once the study is fully unblinded.

“The data announced today provide further support for VX-950’s potential to transform the standard of care in HCV,” said Joshua Boger, Ph.D., Chairman, President and Chief Executive Officer of Vertex. “We look forward to pursuing additional clinical studies in 2006 that will evaluate the ability of VX-950, in combination with pegylated interferon, to achieve sustained viral responses in HCV patients, with a shorter duration of treatment compared to the current standard of care.”

Clinical Plans
Vertex is conducting a broad Phase II development program designed to establish the safety and antiviral activity of VX-950 in studies of up to three months duration. In the next few months, Vertex expects to initiate a three-month Phase II trial with more than 200 participants that will study VX-950 dosed in combination with peg-IFN, both with and without ribavirin, another standard HCV treatment. This three-month study will include a comparison to the current standard of care in HCV treatment. Additionally, a 12-patient, 28-day Phase II trial of VX-950 plus peg-IFN and ribavirin has now completed enrollment and preliminary data from this study are anticipated in the first quarter. In December 2005, VX-950 received Fast Track designation from the U.S. Food and Drug Administration.

About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the liver and blood of people with the disease. HCV, a serious public health concern affecting 3.4 million individuals in the United States, is spread primarily through direct contact with the blood of infected people. Though many people with hepatitis C may not experience symptoms nor be aware of their infection, others may have symptoms such as jaundice and fatigue. Hepatitis C significantly increases a person's risk for developing chronic liver disease, cirrhosis, the need for liver transplantation, liver cancer, or death. Current treatments are commonly dosed for six to 12 months and may be associated with significant adverse events.

About VX-950 and Previous Clinical Data
VX-950 is an oral inhibitor of hepatitis C virus protease, an enzyme essential for viral replication. In 2005, Vertex reported results from a 14-day, Phase Ib study of VX-950 dosed as a single agent in genotype 1 HCV patients. In this prior study, VX-950 displayed potent antiviral activity. After 14 days of dosing, patients in the dose group with the best response (750 mg every 8 hours) achieved a median reduction in HCV RNA of 4.4 log10, a 25,000-fold reduction in viral levels. Adverse events observed in patients receiving VX-950 that were considered possibly related to the drug were mild, and generally similar in frequency to events in patients receiving placebo. The most common adverse events reported in both placebo and VX-950 patients were headache, frequent urination and gastrointestinal symptoms.

Vertex researchers were the first to solve the three-dimensional crystal structure of HCV protease, and have used structural insights to enable the design of small molecule HCV protease inhibitors, including VX-950.

About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company’s strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex’s product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Safe Harbor Statement
This press release may contain forward-looking statements, including statements that (i) VX-950 has the potential to transform the standard of care in HCV infection; (ii) Vertex will pursue additional clinical studies in 2006, including a three-month Phase II trial with more than 200 patients planned for commencement in the next few months, that will evaluate the ability of VX-950 to achieve sustained viral responses (SVR) in HCV patients; and (iii) Vertex will receive preliminary data from its ongoing 28-day Phase II clinical trial in the first quarter of 2006. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause Vertex’s actual results to vary materially. These risks and uncertainties include, among other things, the risks that (i) full analysis of the data, or further testing, will not reflect the interim results reported in this press release, or support any or all of the conclusions provided in this press release; and (ii) clinical trials for VX-950 may not proceed as planned due to technical, scientific, or patient enrollment issues, clinical trial results may not be available when expected, or expected regulatory filings may not occur or may be delayed due to adverse clinical or non-clinical trial developments or unanticipated FDA action; and other risks listed under Risk Factors in Vertex’s Form 10-K filed with the Securities and Exchange Commission on March 16, 2005.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies, and Pegasys is a registered trademark of Hoffman-La Roche Inc.

Vertex Contacts:
Lynne H. Brum, Vice President, Strategic Communications, [phone]
Michael Partridge, Director, Corporate Communications, [phone]
Lora Pike, Manager, Investor Relations, [phone]
Zachry Barber, Specialist, Media Relations, [phone]

Back to the 2006-2005 Press Releases

Vertex's press releases are also available by fax-on-demand at [phone]--Code: 938395

[couldn't think of a nickname]

I have to respectfully disagree that the monotherapy trial wasn't spectacular.
Keep in mind, they were trying to find a good dose. Even so, 4 out of 8 at the 750 mg level got to undetectable status in only 2 weeks. An average 4.4 log reduction in 2 weeks.
SOC can't come close to that. In fact, SOC hopes to get half undetectable in 12 weeks, let alone 2. VL reduction is twice as great in 1/6 the time. That is an amazing leap forward, results never seen before, not matched since.

And, it was only 950. No riba, no IFN.

A leading hepatologist at a liver meeting called it the single most important presentation at that meeting.

Remember, the faster you knock it down, the better the chance for cure.

[Kalio1]

It cant be said what UND levels for SOC are at week two because there are no studies looking at it. Only now are people starting to get a 4 week PCR. They would have to do 2 week PCRs o SOC patients first before you can make such a statement. Many patients clear on SOC tx by week 4. You cant just make up things to try to make VRTX appear better. No data exists but that does NOT mean SOC doesnt clear the virus in 2 weeks for many, maybe it does but they dont test at 2 weeks so we dont know the stats.

[couldn't think of a nickname]

Sorry to disappoint you, I am not making up data to make VRTX look better. Tell me, if they got a 4.4 log reduction in 2 weeks, and SOC avgs 2 logs in 12 weeks (the key marker), how am I making up data?
Models used to predict undet. and SVR use decline slopes. There is no contest between the 2.
If 2 weeks is a bad example, then use 28 days. 12 out of 12 vs. what percent for SOC?

[Kalio1]

Thats the point, there is no data showing how many on SOC clear the virus by week two, so comparisons cant be made. You stated it was superior to SOC in that regard but there is no data on which to base such an analysis.

a dozen people with incomplete data who took VRTX doesnt prove much with NO SVR data. Clearing the virus is only part of the battle, remaining clear is the issue and there is no data at all showing VRTX can do that. If people are waiting on this as a magic answer to Hep C they need more data, provable data to base important health decisions like waiting on drugs that arent even thru drug trials yet to do that. VRTX looks promising, but there isnt any concrete data to show people can SVR using it and you cant legitimately compare two week UND stats if you have no stats on SOC UND rates at two weeks and there is NO data for VRTX SVR rates at two weeks at all. You said that SOC can't do that, I say how do you know? I want VRTX to be the answer but that doesnt mean we can just make up stats to make it appear that is so or that it is "better than" SOC. It seems obvious to me it is far too early to say what VRTX will or wont do regarding SVR, SVR is all that matters.
In addition those taking VRTX in trials now are ALSO on SOC drugs so we still wont know even after the current trials are completed how much VRTX had to do with SVR.

[prettydamscared]

Thanks for the other study and the results with 8 people being dosed with peg & vertex do seem impressive.  There doesn't seem to be any data in that study, unlike the stand alone study, that sugests that a slow increase in HCR-RNA levels took place during post dosing period.

Do you understand my concern that, at this point, why don't we have any svr data on the 28 people that did stand alone vertex 950 in May 05.  That would be 15 months at this point.  I understand they were trying to find proper dosages and they came to the conclusion that the 750 mcg every 8 hours was the most effective.  But no data has been published about svr even in that group, am I right?

It sounds spectacular on the surface but no one seems to be paying attention to the following statement:

Following completion of the 14-day dosing period, a slow increase in HCV-RNA levels was observed during a 28-day post-dosing period in these patients. Twenty-eight days after receiving their last dose of VX-950, there were two patients that had viral levels of more than 1 log10 below their pre-treatment levels."

Is this possibly why we're not seeing svr data on this group?  In the study talked about in the Jan. 9 press release, a portion of the 20 people were dosed with just vertex, but I can't find where it says exactly how many people were involved in that portion of the study.  If'd be nice to have that information, just for the hell of it.

I guess it doesn't really matter at this point.  Bottom line, vertex seems to be much more effective with peg as opposed to without.

Thanks, Char

[couldn't think of a nickname]

Pds, that trial was not for SVR. Viral Kinetics was a secondary end point, the primary endpoint being safety.
None of them treated long enough, and I don't think any went over to SOC that I know of, so there will be no SVR data. Don't expect SVR data that counts for 950 from the other 2 trials either. Those trials only used 950 for 14 and 28 days.
What VRTX has done, is allowed those who got undet. to go over to SOC on their dime for a cure. I don't know what the original 28 were offerred after, if anything.
I would also note that no one, including the company, expected them to ever get SVR. They have said repeatedly that tx was too short.

Kalio:
A+B+C=D.
If VRTX in EVERY trial has gotten 4.4 logs or higher, to undet. status in 2-4 weeks, and done it in almost all of their patients, and SOC gets half undet. by week 12, where is the issue? Your point is that maybe all did there, but the numbers got worse on SOC by week 12? I don't understand.
There is no data from SOC on 2 weeks, there probably is at 4 weeks. If you look at geno 1's ONLY (toughest group) why would one expect SOC to match 950 when it can't even do it by week 12?

SVR data IS the only data that counts. They don't have it yet. Asking for it from before does not matter, and IS NOT LOGICAL.
No one EVER said 950 could do SVR after 2 weeks of dosing. And you know, I am concerned it may take longer than 3 months. Maybe 4, or 5? We don't know.

Here is what we do know.
IFN+riba gets about half undtect. in 12 weeks.
950 plus IFN/Riba get >90% undtect. in 2-4 weeks. Seems pretty clear that 950 was the reason, especially considering what it has done alone. This isn't including the mono. trial.

What you are saying is that you think SOC may have the same response as week 2, but there is no data. Illogical, since it doesn't get the same response at week 12, THERE IS NO WAY it could be better at week 2.
Data takes time, trials need to progress. Eventually they'll have SVR data.
I think you are missing key points here.
I am not making up stats here, there are conclusions that can be safely made.
Frankly, I don't like the accusations.

[couldn't think of a nickname]

The IFN/950 trial, they were rolled over to SOC for 1 year also, if they so choose. They did, they are still being treated. They may not release SVR data for those either, as it can't be used for 950, and in my mind, from a data standpoint, means nothing.

Here is the breakdown you were looking for I think:

Study Design and Results
The 14-day, randomized, blinded, placebo-controlled Phase Ib study enrolled 20 treatment-naïve patients with genotype 1 HCV, the most prevalent and difficult to treat form of HCV infection. Patients were randomized to receive a new tablet formulation of VX-950 at a dose of 750 mg every eight hours (q8h) in combination with a standard dose of peg-IFN (n=8), the same dose of VX-950 administered alone (n=8), or a standard dose of peg-IFN alone (n=4). The median viral load for all patients at study entry was 6.65 log10 IU/mL HCV RNA (approximately 4.4 million IU/mL). Available interim results indicate:

A median 5.5 log10 reduction in HCV RNA in patients receiving VX-950 and peg-IFN for 14 days; 6 of 8 patients had viral levels below the limit of quantitation (30 IU/mL) at 14 days, and 4 of 8 also achieved viral levels below the limit of detection (10 IU/mL).
A median 4.0 log10 reduction in HCV RNA in patients receiving VX-950 alone for 14 days; 1 of 8 patients had viral levels below the limit of detection (10 IU/mL).
A median 1.0 log10 reduction in HCV RNA in patients receiving peg-IFN alone for 14 days; no patients had viral levels below the limit of quantitation (30 IU/mL) at 14 days.


Note: This had a monotherapy arm, 8 patients, and they averaged a 4 log drop also. This trial, they had a higher avg. starting VL.
IFN got 1 log in 2 weeks, 950 got 4 logs in 2 weeks. Both combined, bot 5.5 logs in 2 weeks. That doesn't show additivity, it shows synergy. The sum was greater than the parts.

[prettydamscared]

I very much appreciate your help in clarifying those studies.  Your explanation makes complete sense and I do appreciate your patience in helping resolve my questions. They are actually a little difficult for me to wade through.  Did I mention that I feel like my i.q. level has dropped a point or 10 since the begining of treatment.

If you don't mind me asking, what do you do?

[prettydamscared]

One more thing, I feel like your explanations are logical and based in fact. What I'm trying to say is you've made your point and made it well.  If people don't get it, just let it go.  Just an observation.  (I just don't want you to get frustrated and leave...kinda like being able to bounce things off of you here.)

Thanks again, Charlotte

[couldn't think of a nickname]

Thank you, by your posts (and that you are in the trial) it is obvious to me you want to know all you can.
I am a financial advisor, and started following drug stocks and this area since the mid 90's. Started with the generics, last many years following biotechs. It does help that I know a medical chemist also, and he has experience with HCV drugs.
What helps is that I have followed this particular compound (and many others in truth) before most here have heard of them. So, as time goes by, it seems like old news in a way, even though it might not be for many.
Sorry to let my frustrations out, but there have been some in here that seem to have a bias against either VRTX or 950 for whatever reason. They will tell you I have one for it. If there is, it is a result of looking at this compound for so many years, and determining that it had the best chance for all us. I would call it optomism. And no, I wouldn't let phase 2 data necessarily determine whether one should treat.
A lot to prove, so far, it has cleared all hurdles, and I hope it clears the rest. Nothing is guaranteed in any way. Drugs in phase 2 have about a 30-35% chance of getting to market. It goes much higher in phase 3. That data is courtesy of the FDA I believe, I don't know if I still have the link.

BTW, chemically, Intermune's compound is superior to VRTX's. but it isn't in the clinic yet, and the only thing that matters is data in real people. Schering's looked like it could be better than 950, and that isn't the case.
And, many biotechs are working on drugs to "better" 950, including VRTX themselves. They don't talk much about it, but their second gen. compound is a couple of years behind 950.
The goal is lower dosing, beating resistant strains, and maybe the time factor.
There is a lot going on out there we don't know.

[prettydamscared]

It's so encouraging to know all this is going on behind the scenes.  It actually makes me feel so much more positive and upbeat about our collective prognosis.  I know it's largely about the $$$ for these companies, what isn't, but major changes in treatment seem to be imminent. In what form exactly we don't know but, to be sure, they're coming.  Really exciting stuff!

So, would it be unethical for me to ask you to share your thoughts on investing in some of these endeavors? Oh and btw, don't give a 2nd thought to getting frustrated...I would have been frustrated as well and probably wouldn't have handled it quite as well as you did.

Char

[couldn't think of a nickname]

It wouldn't be unethical for you to ask me, it might not be a great idea for me to answer though. Not for any "inside" knowledge, or anything like that, but it is a regulatory thing.
Thing is, that the "know your customer" rule is critical. That is why I am against radio and tv shows where someone calls in and expects their problems solved by a stranger they talk to for 1 minute, which usually ends with "buy my book". They can be more free than I am.
So many factors matter, and it isn't as simple as which one would make the most money either.
Especially in this area where risk and reward run so high.
I have never talked about the investment opportunities in here, or other forums, because of the above, and if something didn't work out, I wouldn't like that.
And, it isn't only about a particular company. 75% of a stock's movement is because of the overall market, and its sector.

I guess what I am saying is, thanks, I appreciate the sentiment, but it isn't something I am comfortable with. I am not sure it would be fair to you either.

[Kalio1]

I didn't "accuse" you of anything. You stated SOC cant achieve UND status by week 2 and there is no factual basis for that statement. That isn't a accusation it's a clarification. We do know SOC CAN and does create UND status by week 4 (very close to 28 days) in many patients, that is fact. We know at least half of patients can achieve SVR on SOC, that is fact.
It isnt that I "dont get it" at all, the facts are not there to get. Everything we know about VRTX is info put out by the company itself that will be selling the product! ALL of the data you put forth comes from them. Im sorry, but I need facts and independant confirmation before I believe what a company claims about a product they want to sell me so they and their investors can profit to the tune of  billions of dollars especially when my health is at stake. It benefits THEM and their stock price to spin it as the "answer" to HCV but they have no verifiable basis at this point that SVR is even possible or durable and nothing at all from any independant source. The facts do not exist yet that VRTX can create durable SVR in even ONE patient. 12 people clearing the virus in 2 weeks means little if the virus bounces back, we dont know if it will or if it wont. All of this is yet to be known and therefore should be taken with a grain of salt and not as fact. Considering the source of info is the company making the product, the info is clearly going to be biased in favor of the product.

[couldn't think of a nickname]

Ok, you don't trust data by research scientists in trials that are up to FDA standards, so basically, you don't trust ANY trial data because companies can't be trusted.
If you have proof those numbers are not valid, provide it. Otherwise, it is a red herring. When I asked my contact there about getting in a trial, he told me he couldn't help me. They cannot have a part in that. Data is compiled by researchers, and is blinded until the study is over and reported by the researchers at various clinics. Standard Operating Procedure.

I have not seen any SOC data that says people get und. in 2 weeks. and be careful. I don't know how many GENO 1'S get und. on SOC by week 4 either. GENO 2's do not count, as that is easier to treat.
So, basically, you are saying that in all filings with the SEC, and the FDA (which they are held legally accountable for) they are not presenting the facts.

You also don't seem concerned that current data is largely provided by the makers of SOC.

And please stop with this "they don't have SVR in one patient" stuff. No one said they did, no one claims they do. No SVR claims have EVER been made.
It seems that I mention that myself and it gets ignored.
SVR data isn't fact because there is none. VL reduction is, because it has been shown.

[prettydamscared]

You're absolutely right.  I do agree with everything you said.   I'm sitting here laughing, you couldn't be more right.  Of course, you can't randomly willy nilly give a complete stranger such advice.  I shouldn't have asked but I just had to.....Good answer, you handled that well.

Char

[jmjm530]

I understand Vertex will be tested with both combo drugs now, with peg only shortly and perhaps by itself at some point. But I haven't read anything about it being tested without peg and with riba. And I wonder why?

As much as I don't like ribavirin, for me, Peg was the big problem in terms of autoimmune skin issues and also seems to be the culprit for many of the problems people are experiencing post treatment. If I had the choice (and hopefully I never will) to re-treat. SVR odds being equal, I'd much rather treat without Peg as opposed to without riba. I sometimes wonder if the reason they're testing without riba (and with peg) has more to do with what I perceive as the lack of acknowledgement by the medical community of the long-term dangers of inteferon therapy. Or more sinister -- and I'm not a cospiracy theory type of guy :) -- that the big drug companies may have some input into this and therfore championed testing with Peg (their bread winner) as opposed to riba.

My understanding was always that Peg knocked the virus down and riba mutated it so it stayed down. So even on a pharmacological level, seems like riba would be a better companion drug to Vertex as opposed to Peg -- or at least should be tested as such.

-- Jim

[couldn't think of a nickname]

I have stated before, I think the FDA is telling VRTX what they want, and VRTX is doing that. The fastest way to market, is with SOC.  There is a strong push to get these new drugs out, and the makers of IFN have nothing to do with this. In fact, they would need 4x as many people to tx for 3 months than now to essentially break even. That doesn't even include those today who re-treat.
And then there is Albuferon. So, the makers of IFN know their days of dominance are likely numbered.
IFN is being used because it has the antiviral effects, and riba is not well understood. But, it is not an antiviral.
IFN is known to be sensitive against mutant strains, particularly the A156T strain that had PREVIOUSLY shown up in VRTX trials, although it was less fit, and also is a good boost.

Neither drug is pleasant (IFN or riba), but for me, I won't take riba, with thalassemia minor. My hgb last month was 12.2. Imagine after riba gets a hold of it.

From VRTX's standpoint, right now, their goal is to get a good cure to market ASAP, to beat their competitors (note to some, this is a good thing).
Their next gen compound, or competitors compounds might be better suited for a monotherapy.
And, a monotherapy (today) might require longer treatments, lesser SVR, etc, so trials would take longer, burn more money.

I am not a conspiracy theorist. But I am very cognizant of what goes on in this area. If those want to spew venom (not you jim) at drug companies, Wyeth is a great one to do it. None of you know how much garbage they did, and I am sure for as much as I know, there is a lot more.

What bugged me earlier in this thread was that it was ok to trust one set of published data, and not another. It is ok to be skeptical, but there is that innocent until proven guilty thing.

[couldn't think of a nickname]

I know you weren't commenting in that light.
I guess I did want to vent against Wyeth though, as I haven't forgotten some of their skeletons.

If they just did the monotherapy, it would be a longer, less-sure route to market, and VRTX has told me that their goal is to keep the IFN as short as possible, due to cumulative effects. No doubt, as everyone in here who has had it (and I can't speak from experience), IFN affects most from day 1.
I have a cousin who took IFN (don't know the dose) for 2 years due to cancer, but doesn't anymore. He won't talk about it though, so unfortunately, I can't really get info from him.

This is why I really hope that Albuferon does well and gets to market with or before 950 (assuming both make it on their timelines). It would be a huge step IF (if, if, if) you could take 950 for 12 weeks, with only 6 shots of Albuferon. At least it wouldn't be 48. This is the absolute best case scenario IMHO right now. Then, the next gen of HCV drugs could go after monotherapy. And it could take a comob approach, maybe ITMN's candidate, or a polymerase inhibitor with a PI. I think VRTX had mono. as their original goal, but data, and the regulatory authorities I am sure have steered them the other way.

It is only MHO, but I think they are getting very strong guidance and I know they are getting good dialogue from the FDA. These drugs and this disease do seem to be a priority (or at the very least more of one) than in the past with these new compounds. Even if it seems (and we do) have a lack of good advocates.

I don't want IFN either. Not with my history of allergies and tendency towards fibro.

I just wish that there were a lot more focus on life after AFTER SVR, and longer term effects. Unfortunately, that side of the equation isn't pushed enough.

And I hope and pray that all those with SVR do recover from the nasty sides. A cure should also mean feeling better.

[mremeet]

IMO so called "monotherapies", especially in regard to VX950, will not be a commonly implemented strategy for many years, if ever really. The likely initial approved usage of VX950 will almost certainly be with peg IFN with or without riba. By that time other PI's will likely be coming online too. At that point combining the best PI's will probably become a very appealing and possibly extremely effective strategy too. Plus there are so many other new drugs being researched and coming along, that the options for a myriad of other combinations will also become possible. This gives rise to a bit of a quandary though, so many new drugs coming online within a 3-7 year timeframe will start to greatly increase the total possible number of combinations of these various drugs. But none of them can be dosed in combination unless they have been completely and successfully tested in whatever combination has been deemed worthy of evaluation. When you think of all the possible ways to combine all the various drugs, you can quickly end up with a colossal test matrix with all kinds of dosage/duration permutations, which would cost a huge fortune and a very long time to fully carry out and evaluate. This process could take years and years. As just one example, what if albuferon, VX950 and SCH503034 were to be combined? It's probably unlikely Vertex is going to be willing to participate in a combo trial with a competing PI manufacturer before their drug is approved and on the market. So assuming VX will be out in 3 years, give another year for them to establish market share (dominance more like) and formulate new test protocols, then it would probably take at least another 2-3 years to get these tested and approved. All told probably close to 7-9 years (from now) before just one of these combinations might come to market.

But, all in all it is good to be in the position where all of these drugs seem to be successfully moving to the forefront, and with more good news all the time suggesting even better advancements for the future. This is a very exciting time for HCV research, I feel there will likely be what will largely constitute an outright cure for nearly all of us within 10 years, and for most of us within 5 years. I think we’re living in a time when HCV still has a strong and fearful hold on many of us, but in not so many years it will soon go the way of Polio. I pray we all make it to see the glory of that day!

[couldn't think of a nickname]

Good post, and I can tell you why drugs like SGP's and VRTX's will not be tested pre-market. No drug company will spend the money or waste their time on drugs that aren't approved. I asked if VRTX had considered testing with Albuferon, and they flat out said no, too much room for failure. If they test with an experimental drug, they are screwed if the OTHER drug flops.

As far as after, that would be possible, and does happen. Look at the new HIV pill that actually combines 2 or 3 drugs into 1 pill. For VRTX, it would be no skin off of their back, as there's looks to be the cornerstone. SGP is a different story, as they are testing for 48 weeks, and doing a combo in shorter time hurts their projected revenue stream.

And, I have said many times, the next gen of drugs are being developed, but not talked about. VRTX finally had to admit they had one, in response to analyst's questions after the J&J deal.

And, many may not realize this, but 950 is actually already a second gen. drug. MMPD was their first, and they were combining it with SOC. They stopped the program, because 950 is light years ahead of it, and was actually about to pass MMPD's timeline. They completed phase 2, and decided not to waste time, money, and resources on phase 3. It was a good businees decision.

[jmjm530]

Probably not necessary, but to clarify anyway, my post had nothing to do with previous discussions in this thread and in no way was a negative reflection on Vertex or the company.

It was just that for me -- and I'm sure others -- interferon is a more troublesome drug than ribavirin, and since they're testing it in Europe without riba, I wondered why they weren't testing it somewhere without peg. My guess is that this will happen at some point depending of course on how well the trials go. On a theoretical level, I would never again treat with any more than 12 weeks of interferon (and wouldn't be all that happy even with that) but riba, while no day at the beach, I don't think did me any long-lasting harm.

-- Jim

[couldn't think of a nickname]

I should add, that 950 and SCH are both being tested with Ritonavir. Rit. has a boosting effect with HIV drugs, to lower dosing, and early tests indicate it would do the same with the above drugs. This is a case of drugs being tested together, but one of them is already known and approved. Ritonavir acts to slow the elimination of the drug from the liver, to allow less frequent dosing. In the example of 950, it might allow 1 or 2 times daily dosing. I am not sure if ritonavir would work with polymerase inhibitors, but it does work well with Protease inhibitors.
Tests are ongoing with that combo.