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>> "The mild increases in ALT at the 400 mg/week dose likely reflect extreme lipid-lowering activity, not toxicity, and are consistent with perturbations in liver chemistries seen with statins."
Does anyone know of the scientific basis for this claim? The implication that the liver enzyme elevations occasionally seen with statins are related to the drugs working so well on lipid lowering seems far fetched to me. <<
Just a guess , but might it be a result of 'de-fatifying' fatty livers , resulting in temporary leakiness ?
I get the impression that ALT elevations resulting from statin therapy are becoming less troubling to the medical community as experience with their usage accumulates , especially if it resolves over time. Some even question the need for regular monitoring of liver enzymes since it rarely justifies a change in therapy , though elevations are much less common in currently prescribed statins relative to what was seen here. Still , I'm not convinced this will be a deal-killer , considering the activity at lower dosages.
Osiris phase 1 heart study
http://biz.yahoo.com/bw/070325/20070325005045.html?.v=1
Osiris Therapeutics Announces Positive Results in Groundbreaking Stem Cell Trial to Treat Heart Disease
Sunday March 25, 12:00 pm ET
Intravenous Therapy Resulted in Statistically Significant Improvement Over Placebo in Multiple Safety and Efficacy Endpoints
BALTIMORE--(BUSINESS WIRE)--Osiris Therapeutics, Inc. (Nasdaq:OSIR - News) today announces positive six-month results in a groundbreaking clinical trial evaluating PROVACEL(TM), an adult mesenchymal stem cell (MSC) therapy for the treatment of heart disease.
In a 53-patient, double-blind, placebo-controlled study evaluating the safety and preliminary efficacy of the intravenous administration of PROVACEL, heart attack patients receiving the therapy had significantly lower rates of adverse events, such as cardiac arrhythmias, as well as significant improvements in heart, lung and overall condition. Joshua Hare M.D., the trial's lead investigator, presented the data this morning at the American College of Cardiology's Innovation in Intervention: i2 Summit.
"We are extremely enthusiastic and encouraged by the degree to which these results indicate that MSCs are not only safe, but also appear to clinically improve patients who have suffered a heart attack," said Dr. Hare, who is the Lemberg Professor of Medicine at the Miller School of Medicine, University of Miami; Chief of the Cardiology Division; and Director of the School's Interdisciplinary Stem Cell Institute. "The results consistently show patient improvement with regard to heart and lung function, and indicate global improvements in well-being. These findings strongly support the ongoing development of PROVACEL for acute myocardial infarction and possibly other forms of heart and lung disease."
C. Randal Mills Ph.D., President and CEO of Osiris Therapeutics, said: "We were confident in the safety profile given our previous experience using the intravenous form of these stem cells to treat other diseases in later stage clinical trials. However, the magnitude of the across-the-board improvement was surprising. These data further validate the broad clinical applicability of our stem cell technology. Based on these encouraging results, we have started working on the design of the next stage of clinical trials."
Trial Highlights
Administration of PROVACEL was found to be well tolerated at all dose levels.
Patients in the PROVACEL group were four times less likely to experience an arrhythmic event compared to those receiving placebo (9% vs. 37%, p=0.025).
Fewer patients experienced clinically significant premature ventricular contractions after receiving PROVACEL as compared to placebo across all time points (11% vs. 24%, p less than 0.001).
PROVACEL patients with major "anterior wall" heart attacks had a statistically significant 7.0 point (24%) improvement in ejection fraction at three months and a 7.3 point (25%) improvement at six months over baseline (p less than 0.05), while similar patients receiving placebo did not have significant improvement.
Patients receiving PROVACEL had significantly improved lung function as measured by improvement in FEV1 % predicted values (17 point PROVACEL vs. 6 point placebo, p less than 0.05).
Significantly more patients who received PROVACEL experienced improvement in their overall condition at six months as compared to those receiving placebo (42% vs. 11%, p=0.027).
"The data speak for themselves," said Timothy Henry M.D., Director of Research at the Minneapolis Heart Institute Foundation at Abbott Northwestern. "This was a carefully executed, double-blind, placebo-controlled trial where patients who received the stem cells simply did better. The results are fascinating, particularly given the route of administration, and lead us to challenge our basic assumptions about cell therapy for heart disease."
Safety Data
Administration of PROVACEL was found to be well tolerated at all dose levels evaluated. There were no patient deaths, and no toxicity was observed with the administration of PROVACEL. Importantly, there were fewer adverse events in patients receiving PROVACEL as compared to placebo (5.3 vs. 7.0 adverse events per patient). Patients receiving placebo required repeat hospitalization sooner and more often than those treated with PROVACEL (31.5% at an average of 66 days vs. 23.5% at an average of 120 days). There were no serious adverse events attributed to the drug.
"Unlike other cell therapies that have been used in the heart, these cells are readily available when we need them and are administered through a standard IV line like many of the other drugs we give our patients," Jay Traverse M.D., principal investigator and Assistant Professor of Medicine at the University of Minnesota. "If the safety and efficacy profile remains strong, the practicality of the treatment model clearly supports wide-scale use."
Arrhythmia Data
Patients enrolled in the trial were monitored for the occurrence of cardiac arrhythmia. Patients in the PROVACEL group were four times less likely to experience an arrhythmic event compared to those receiving placebo (9% vs. 37%, p=0.025). Of particular interest, half of the arrhythmias noted in the placebo group involved the ventricle, or blood pumping part of the heart, while only 14% of the arrhythmias in the PROVACEL group involved the ventricle. Ventricular arrhythmias are associated with scar formation in the affected portion of the heart following a heart attack and can be a sign of poorer prognosis.
The anti-arrhythmic effects of PROVACEL were also seen in the number of premature ventricular contractions (PVCs) observed. Patients treated with PROVACEL had fewer PVCs at all time points after day 10, despite having more PVCs at baseline. The percentage of patients who experienced clinically significant PVCs (greater than 10 PVCs per hour) was also significantly less in those patients receiving PROVACEL as compared to placebo (11% vs. 24%, p less than 0.001) and was most pronounced at the one-month (6% vs. 32%, p less than 0.05) and two-month (9% vs. 38%, p less than 0.05) time points. Patients often experience an increase in the number of PVCs following a heart attack, corresponding with the formation of scar tissue in the heart.
Performance Data
Preliminary echocardiogram data demonstrated that patients with clinically significant heart attacks involving the anterior wall had pronounced improvement in left ventricular ejection fraction (LVEF) not seen in patients receiving placebo. Patients treated with PROVACEL had a statistically significant 7.0 point (24%) improvement in LVEF at three months and a 7.3 point (25%) improvement at six months over baseline (p less than 0.05). This compared favorably to the 2.9 point (6%) and 3.4 point (8%) improvement found in patients receiving placebo, neither of which was significant over baseline.
Overall, patients treated with PROVACEL had an 18% improvement in LVEF at three months compared to an 11% improvement for the placebo group. The improvement observed in the PROVACEL patients was statistically significant over baseline (p less than 0.005), and the effect was maintained through six months, at which time LVEF was 19% higher than baseline.
The positive differences observed in arrhythmias and the echocardiogram were consistent with the more practical assessments used in the study. A greater proportion of patients had prompt heart rate recovery (less than 15 minutes) following a six-minute walk test when treated with PROVACEL as compared to placebo at the six month time point (55% vs. 26%, p=0.08).
Finally, the patients' overall condition was assessed by the treating physician for signs of improvement or deterioration. In this global assessment, significantly more patients in the PROVACEL group experienced improvement in their overall condition at six months as compared to those receiving placebo (42% vs. 11%, p=0.027).
Pulmonary Data
Lung function tests were performed to monitor subjects for potential adverse changes related to the treatment. Surprisingly, patients who received PROVACEL had significantly improved pulmonary function following treatment compared to placebo as measured by improvement in FEV1 % predicted values (17 point PROVACEL vs. 6 point placebo, p less than 0.05). Preclinical studies performed at Osiris Therapeutics had previously demonstrated that the anti-inflammatory and anti-fibrotic (anti-scarring) effects of the stem cells may be of benefit to patients with conditions such as Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF). However, this finding is the first placebo-controlled evidence in humans that indicates MSCs may play a beneficial role in the treatment of certain lung disorders.
The PROVACEL trial is one of five ongoing clinical trials at Osiris, including two Phase III trials using the cells in the treatment of steroid refractory Graft vs. Host Disease and Crohn's Disease, both of which have been granted fast track status by FDA. Osiris is developing PROVACEL as part of a strategic alliance with Boston Scientific Corporation (NYSE:BSX - News) for commercialization of Osiris' mesenchymal stem cell technology in the cardiac field.
Evaluation of patients in the PROVACEL trial will continue for a total of two years following treatment.
Webcast and Conference Call
Osiris has scheduled a web cast and conference call to discuss the results on Monday, March 26, at 9:00 AM ET. To access the web cast, visit the Investor Relations section of the company's website at http://investor.osiris.com/events.cfm. Alternatively, callers may participate in the conference call by dialing 800-810-0924 (U.S. participants) or 913-981-4900 (international participants).
Motley Fool on IDIX
"This chart shows a handful of companies whose shares have plummeted within the past year -- despite analysts' expectations that they will grow at better than a 25% annual clip."
http://tinyurl.com/2b9r9a
(Shows IDIX with 5-year projected growth rate of 29%)
>> Delaware law affords substantial protection from a lowball takeover. <<
For such a little state , Delaware is pretty influential when in comes to corporate law , isn't it ?
I'd like to learn the essence of the protection that remains after the standstill expiration , though I realize I'll never be mistaken for 'smart money' even if I do.
We must lose something with the standstill expiration , otherwise we wouldn't be talking about it , correct ? I would assume that NVS will have substantial freedom to purchase shares on the open market then , at least up to some limit. If so , they will benefit by a low share price.
I also understand that NVS has a vested interest in seeing the drug development move forward. My concern is that as we get closer to the expiration date , the calculus regarding development progress versus cheap shares will start to shift.
>> Fortunately, we have another 14 months until the standstill agreement expires. By then, the picture could be very different. <<
Different in a good way (for us ) , right ?? :)
Seriously , though , the longer the share price remains depressed and the closer we get to the end of the standstill , the more investors will wonder if NVS is gaming IDIX for a takeover at a bargain price.
As a dyed-in-the-wool conspiracy nutcase , I'm already wondering , but I worry that rational people will also before too much longer.
>> The basic idea is that people with a financial stake in the outcome should not be entitled to vote. Duh. <<
About time.
Thus the question becomes:
Is there a ( non-conflicted ) doctor in the house ?
Re : interstitial pneumonitis
In just a little googling on this I get the impression that this condition may be largely cytokine-related , with many similarities to sepsis. Steroids are obviously aimed at damping down this reaction but specific immune deficiencies may contribute as well , paradoxical as that may sound , and correction of these deficiencies with the appropriate CSF(s) , iv gamma-globulin , etc. , might help.
An example in HIV-related lymphoma :
"Persistent Panhypogammaglobulinemia After CHOP-Rituximab for HIV-Related Lymphoma "
http://jco.ascopubs.org/cgi/content/full/23/1/247
Re : interstitial pneumonitis
( Corky - I got the following by private message by mistake , as I'm sure it was meant to be sent to you. I hope zeta1961 doesn't mind my posting it here ; as a freebie iHubber it was my only way to get it to you. )
Sent By: zeta1961 Date: 3/21/2007 3:33:47 PM
Hi Corky..I lurk this board but don't ever post here..
I assume your brother is being treated with steroids?..it's the only treatment I know of that is standard and usually helpful..here's a paper on it from 2005..I know some ICUs will do some sort of heart bypass( a modification of it) but it's usually a last resort and only if the intensivists feel gutsy because of the obvious risks..I"m a nurse and used to post on the IMCL ymb from time to time as 'obliteratecancer'...
Can I ask which hospital he's in?
http://annonc.oxfordjournals.org/cgi/content/full/16/8/1399
corky ...The only thing I can offer is sort of obvious... If you don't have absolute confidence in your brother's doc(s) , I'd try to get a consult ASAP , even by phone if necessary , from someone who's a recognized expert in this condition.
Best of luck to you and your brother.
Boger Bucks for Bio Building
( Prospects at VRTX must not be too bad. )
http://tinyurl.com/yrkfar
Wesleyan Gets $2.5 Million Gift
By DANIELA ALTIMARI
Courant Staff Writer
March 21 2007
MIDDLETOWN -- A Massachusetts biotech entrepreneur who graduated from Wesleyan in 1973 has pledged $2.5 million for a new science building at the university.
The gift from Joshua Boger and his wife, Amy Boger, will help fund the design of a molecular and life sciences building to replace the aging Hall-Atwater Laboratory. The new building is expected to provide at least 175,000 square feet of space and to cost at least $125 million. Construction could begin in 2009, according to the university.
Once complete, the building will significantly enhance Wesleyan's rigorous and respected science program, said university spokesman David Pesci. "We believe that this new science facility is essential to help us continue to draw the types of students we've been able to draw," he said. "Having a state-of the-art lab ... would put us at the very top of universities in our peer group."
Boger is the founder and chief executive officer of Vertex Pharmaceuticals. His love of science blossomed at an early age, according to the press release put out by Wesleyan announcing the gift. As a boy of 9 he grew potassium permanganate crystals in a lab he set up above the family garage. He also swabbed the mouths of neighborhood playmates and grew cultures in his mother's refrigerator.
"If you had asked me then if I was going to be a scientist, I wouldn't have understood why you were asking," he said in the press release. "It was simply that science was a fun thing to do."
After leaving Wesleyan, he earned a doctorate in chemistry from Harvard and took a job at Merck. In 1989, he left to launch Vertex, which is based in Cambridge and is currently conducting clinical trials of a drug to treat hepatitis C. The company is also developing several other drugs, including possible treatments for rheumatoid arthritis and cystic fibrosis.
Contact Daniela Altimari at altimari@courant.com
Copyright 2007, Hartford Courant
--------------------------------------------------------------------------------
Feuerstein on VRTX
http://www.thestreet.com/newsanalysis/biotech/10345652.html
Vertex Shareholders Stay Vexed
By Adam Feuerstein
Senior Writer
3/21/2007 7:57 AM EDT
New clinical data from Vertex Pharmaceuticals (VRTX) regarding its hepatitis C drug telaprevir, expected at a medical meeting next month, seem to have investors on edge.
Shares of the Cambridge, Mass.-based biotech firm continue show weakness on worries that telaprevir won't live up to expectations when new phase II data are presented at the European Association for the Study of Liver Disease meeting on April 11-15.
I last wrote about telaprevir in early February with Vertex shares at $35, at the time down from a recent high of $44. On Tuesday, the stock closed up 20 cents at $27.85.
Like then, there doesn't seem to be a specific nugget of negative information about telaprevir forcing Vertex lower (at least not that I've been able to pick up). Instead, there's a general uneasiness -- even confusion -- about the telaprevir data that Vertex will bring to the EASL meeting and how it will be interpreted by hepatitis C experts and investors.
At the risk of coming off a bit too wonky, I want to preview Vertex's upcoming EASL presentation. It may not dispel any fears, but with any hope it will make interpreting next month's data easier.
The most highly anticipated news will come from what is known as "Arm D" of Vertex's Prove 1 study. In this arm, 20 treatment-naive hepatitis C patients (those who have never taken anti-hepatitis C drugs) were given a triple combination of telaprevir plus interferon alpha and ribavirin (the latter two drugs representing the current, standard hepatitis C treatment.) Patients in this arm of the study were treated with all three drugs for 12 weeks, then all treatment was stopped.
Twelve weeks after stopping treatment, patients are being analyzed to see whether the hepatitis C virus in their system remains at undetectable levels. In hepatitis C circles, this is what's known as a "sustained virologic response," or SVR. Since SVR, in this case, is being measured 12 weeks after treatment ends, the data that Vertex will share at the EASL meeting will be SVR12 (from Arm D of the Prove 1 trial, to be exact.)
"This will be the first time in a clinical trial that any [hepatitis C] infected patient will have systematically been stopped at 12 weeks to see whether or not they can achieve SVR or not," explained Vertex's Chief Medical Officer John Alam at an investor conference last week.
What makes these data so intriguing is that they represent Vertex's home-run strategy with regard to telaprevir, because 12 weeks on a drug would be the shortest treatment ever conceived for hepatitis C patients. Currently, hep C patients, like those enrolled in Prove 1, need to be treated for 48 weeks with interferon and ribavirin before they can be cured.
Naturally, an aggressive stab at a 12-week treatment schedule is a risky strategy for Vertex, so the other arms of the study are exploring different treatment regimens: all dose telaprevir for 12 weeks like in Arm D, but they also extend interferon-ribavirin treatment for longer periods.
Believe it or not, that's the easy part of understanding the upcoming data. Now, we get to the complexities.
If all 20 patients in Arm D of the study were to make it through 12 weeks of treatment and 12 weeks of observation, interpreting the SVR12 data would be relatively easy. We'd just take the number of patients with undetectable virus and divide by 20 to come up with an answer.
Unfortunately, it's very possible (and probably likely) that not all 20 patients in Arm D make it through 12 weeks of treatment. (And remember, these patients are getting telaprevir, interferon alpha and ribavirin.)
According to criteria built into the Prove 1 study design, Arm D patients have to achieve undetectable levels of virus at four weeks and 10 weeks of treatment in order to stop treatment altogether at 12 weeks. If a patient doesn't meet this interim efficacy hurdle, doctors will order patients to continue receiving interferon and ribavirin for an extended period beyond 12 weeks.
Since these "nonresponding" patients will still be receiving treatment for their hepatitis C, Vertex won't be able to analyze them for SVR12 response. The denominator for the Arm D analysis, therefore, will be something less than 20 patients.
And this is where investors will have to pay close attention to how Vertex reports the data. Here's why:
Let's assume that Vertex tells us that 13 patients in Arm D achieved an SVR 12 weeks after stopping treatment with telaprevir, interferon and ribavirin. Furthermore, Vertex tells us that four patients were deemed "nonresponders" and are therefore still being treated with interferon-ribavirin beyond 12 weeks.
What's the SVR12 result for Arm D of the study? Using the most generous analysis, the SVR12 would be a robust 81% (13/16 patients). But using a stricter calculus, the SVR12 would be a less rosy 65% (13/20 patients).
For this reason, pay attention to both the numerator and the denominator used to analyze the upcoming telaprevir data. There are pros and cons for using either calculation, which go a long way toward explaining why there's so much uncertainty about the upcoming presentation. (And I did warn you that this column would get wonky.)
Other things to keep in mind about the upcoming data:
Pay attention to the side-effect profile of telaprevir and the reporting of any toxicities or adverse events that might have caused patients to discontinue treatment.
The SVR12 data will be a good measure of telaprevir's efficacy, but it's not enough. For a hepatitis C drug to receive FDA approval, patients must have undetectable virus for 24 weeks, or six months, following the end of treatment. Generally speaking, about 50% of treatment-naive hepatitis C patients are cured (achieve SVR24) on the currently marketed drugs.
If Vertex doesn't succeed with its home-run strategy of treating patients for only three months, the game is far from over. As I said above, the majority of patients in the Prove 1 study are being treated with three months of telaprevir in combination with either 24 or 48 weeks of interferon and ribavirin
>>> The CMO leaving though, leaves one to wonder if all is well at IDIX. Is NVS beginning to call all the shots within corporate management? <<<
I agree that it takes more than 2X as much rationalizing to explain the departure of two execs compared to just one. When the third one leaves --- um , let's not go there.
The idea of NVS taking the reins is a definite possibility. Someone at IDIX screwed up with NM283 , as they should have planned for testing triple therapy including riba from day one. JP tells us there's no scientific rationale for an interaction between NM283 and riba. If that's true , then what was the strategic rationale for waiting so long to initiate triple therapy studies ?
It might not be much fun to work at IDIX right now if they're feeling the heat from NVS. Maybe that's why JP sounded a little testy on the recent CCs.
As go_seek would ( and will ) say : " Ouch ! Again ! "
I don't know how the market will react , but it seems to me that NM283 is discounted to near zero already.
Maybe uptake of Tyzeka is not going as expected. Or , maybe he just got an offer he couldn't refuse.
I'm going to hold thru EASL anyway , barring another knife in the gut before then.
Re : Cramer
A slime mold in dress shirt and tie.
Market manipulation , price fixing by corporations , etc. -- all OK by him , just the way we play the game.
Notice the way the ignoramus won't let Task get in a word edgewise -- Cramer is too eager to hear what Cramer will say next !
Youtube is providing a service in exposing this.
Re : Cellular Visions: The Inner Life of a Cell
The Harvard site has the video with a voice-over description :
http://multimedia.mcb.harvard.edu/media.html
>> no reports of prostatitis were made as part of the side effects if patients that did not have their prostates surgically removed were enrolled... <<
croumagnon,
In patients with prostate cancer who still have their prostates , I'd guess that prostatitis is the norm since cancers often induce inflammation , though it's likely a nonspecific and ineffective response in established tumors. Many believe this nonspecific inflammation encourages tumor growth. If Provenge induces a specific antitumor response , it may do so with much less overall inflammation , as the specific response displaces the nonspecific. Either way , if I was taking Provenge and my prostatitis got worse , I'd say : "It's working ! ". :)
I'm surprised the issue of surgical removal as an inclusion criteria has just come up because it does raise some interesting questions about response to therapy. I suppose we'll have some answers in a couple weeks.
Check out this post on the MOA of ampakines...
Complex , but elegant :
http://www.investorshub.com/boards/read_msg.asp?message_id=17980348
>>> The SEC's goal in creating automatic trading plans was to allow executives to sell shares without triggering insider trading charges. <<<
So , they created trading plans which :
"allow executives to end plans before they've been fully executed, set up multiple short-term plans, and begin selling immediately after adopting a plan."
I'd say the SEC met its goal.
The net effect is that insider trading is perfectly legal , as long as you give it a different name. Sort of like the way bribery is legal if it's called " campaign finance " or " lobbying ".
Jeez , the price we're willing to pay for a free market...
>> My guess for the rationale is this: not having a control arm speeds enrollment, both by reducing the total number of patients and by giving prospective patients a larger incentive to enroll. <<
Thanks , Dew.
I suppose that might be it , but with five arms in the trial currently , at 35 or so patients each , it seems like adding another 35 for an SOC arm wouldn't have slowed things down that much , and any enrolling patients would only have had a 1 in 6 chance of receiving SOC. IDIX makes a big deal about not unblinding data to maintain the integrity of a trial , but in leaving out the SOC arm they open themselves up to questions about the overall significance / validity of results.
Assuming the nonresponder results give us some clue about the relative relapse rates of NM238/ifn compared to SOC , it will still be difficult to project SVR rates for the naive trial based on the 48 wk. viral load data because there is no SOC comparator , and thus the issue of patient demographics becomes a critical , and at least partly unknown , variable.
Still , if the 68% Taqman negativity figure holds up thru wk. 48 , and the nonresponder study gives us reason to think that relapse rates are similar or better than with SOC , we'll have some basis for optimism about SVR results in the naive trial.
I'm still looking at NM283 as a lottery ticket and the current valuation of IDIX suggests that the market does as well , but I think (hope ?) Tyzeka sales will drag the share price north , eventually. .
Speaking of questions...
Does anyone know if IDIX has ever explained why they have a SOC arm in the nonresponder study but not in the naive study ?
It seems to me that a study would have greater supportive value in the eyes of the FDA if it included a control arm.
This part of the Q&A session was classic :
>> Question: Can you talk about the nature or remind me of the nature of the discontinuations of the interaction study and was either of them related to NM283?
Answer: There is one discontinuation of a patient taking -- we don't know what they were taking because it was a blinded study. <<
LOL
Sometimes I think trial results are unblinded to everyone but me.
>>> How was / is the "10-100x better" determined?
in the lab... culture / test tub? <<<
1) Insert hand in butt.
2) Grasp data.
3) Remove hand and present data.
They could be talking about 1-2 log better viral load reductions per a fixed time period in the replicon system , or they could be talking about a 1-2 log better EC50 , i.e. , higher specific activity , which allows lower dosages.
I wouldn't put too much faith in the numbers or worry about it too much at this point. A lot can go wrong between now and filing of an NDA , as we're seeing with NM283.
It's always good to have a pipeline of candidates , however.
>> why do people who were imprisoned for long terms early in life generally look younger than their age when they are released? <<
Low stress , healthy diet , plenty of exercise , and intellectually stimulating environment ?
And lots of very close friends.
>> Final SVR data will be available <<
I hope they do present the SVR data for the tx.-refractory patients , even though it's probably going to be weak.
It should give us some idea about relapse rates of NM283/ifn as compared to SOC that we can use to handicap the naive trial.
I'd be content with a P3 that was simply delayed another quarter or so , but my gut feeling is that the only viable path to P3 is triple therapy , and the available evidence-- the recent replicon interaction study and the older BVDV NM107 interaction data -- combined with JP's changing tone in the last few presentations , leads me to think that even the triple therapy path is a long shot absent some additional dosage/admin studies to optimize the combo.
The Halt-C studies showed that reduced riba dosing had little or no effect on SVR rates , as long as riba was not discontinued ( even briefly ). Thus there may be room to manage any interaction that may exist , but it would likely require more study.
Or , maybe they (we) get lucky.
:)
>> Why don't they try Tykerb WITH Hercetpin, before the Herceptin stops working? <<
blade,
I don't follow this area so I can only speculate that they probably will try the combo , now that Tykerb is approved.
Aside from cost and the possibility of SAEs that limit the combo approach , the only argument I can think of against it is if it's known that a single mutation can confer resistance to both agents , in which case sequential monotherapy to tx. failure followed by combo therapy might make more sense.
Maybe someone else more familiar with the field can chime in.
FDA Approves Advanced Breast Cancer Drug
http://tinyurl.com/299lsj
By ANDREW BRIDGES
The Associated Press
Tuesday, March 13, 2007; 5:00 PM
WASHINGTON -- Women with an aggressive form of advanced breast cancer that other treatments have failed to stop gained a new option Tuesday with the approval of a novel drug _ but how much benefit it offers is unclear.
The GlaxoSmithKline PLC drug, Tykerb, is to be taken once daily in pill form and is meant for women who have received prior treatment with the intravenous drug Herceptin and older chemotherapy drugs called taxanes and anthracyclines, the company said. The Food and Drug Administration said it approved Tykerb for use in conjunction with the chemotherapy drug Xeloda.
Glaxo said Tykerb would be available in two weeks. It will cost about $2,900 a month, the company said.
The initial results of a study reported last year showed that Tykerb in combination with Xeloda delayed tumor growth for an average of 8 1/2 months, or about twice as long as Xeloda alone. Tykerb worked so well that the international study was stopped early and all participants were offered the drug. However, Glaxo said a later analysis of the results of that study showed the delay actually was closer to nearly seven months for women on both drugs, versus almost five months for those on Xeloda alone.
The FDA said it was too early to know if women taking Tykerb and Xeloda would live longer than those taking the latter drug alone.
The lack of that information has left one advocacy group disappointed. Survival _ and not progression of disease _ gives a truer picture of a cancer drug's efficacy, Barbara A. Brenner, the executive director of Breast Cancer Action, told the FDA in a March 5 letter.
"The FDA should not approve drugs that have not shown either a survival benefit or improved quality of life for breast cancer patients with metastatic disease," Brenner's letter read in part.
FDA drugs chief Dr. Steven Galson said Tykerb expanded the options available to women with a type of advanced breast called HER2 positive when it has metastasized, or spread.
"Today's approval is a step forward in making new treatments available for patients who have progression of their breast cancer after treatment with some of the most effective breast cancer therapies available," Galson said.
Tykerb, like Herceptin, is part of a new generation of cancer medicines that more precisely target tumors without killing lots of healthy cells.
Herceptin has been an important option for many women with advanced, HER2 positive breast cancer, but eventually it stops working and women succumb to the disease.
Both drugs target a protein called HER-2/neu, which tumors make in abnormally large quantities in roughly one-fourth of all breast cancers. While Herceptin targets the outside of the HER2 protein, Tykerb works from the inside of the cell.
Because of that difference, Tykerb works in some HER2 positive breast cancers that have been treated with Herceptin but no longer benefit from the older drug, the FDA said.
Generally, women with HER2 positive breast cancer face a greater risk of disease progression and death. Approximately 8,000 to 10,000 women die from metastatic HER2 positive breast cancer each year, the FDA said.
Xeloda, or capecitabine, is made by Switzerland's Roche Holding AG. South San Francisco-based Genentech Inc. makes Herceptin, also known as trastuzumab.
IDIX at Cowen
Just listened to the replay. IMO , JP is progressing , with each presentation , to the point where he will finally reveal that there will be no P3 for NM283 beginning in 2007. It is no longer even listed as a 2007 goal. It's all about being in position to be a part of the new combination therapies of the future. Although the data is supposed to be blinded , I get the impression that he's not all that hopeful. My guess is that he's either seen some of the human interaction data or that animal model studies have been less than stellar. I hope I'm wrong , of course , but my assumption going forward is that there is no path to approval for NM283 combined with pegifn or pegifn plus riba. In any case , we won't know the interaction data results until late May , if released by PR , or June if released at AASLD.
He said that he thought that first-year Tyzeka mkt. share would probably look about the same as first-year entecavir did.
EOY 2007 cash projected at $100-110 mill.
>>> What does sub-prime lending have to do with biotech? <<<
I don't get it either.
It's like that thing with the canary. What does a dead canary have to do with coal-mining ?
Re: Quiz
>>> (Sorry) <<<
That , sir , was an understatement.
WAG update : What Biowatch said.
WAG : AKZO needs the money to retrofit their manufacturing plants to comply with tougher environmental standards ?
Citi / Werber on VRTX
( courtesy erasmus on VRTX IVillage )
Citigroup Reports
* We spoke w/mgt concerning the presentation of PROVE 1 data at a late-breaker session on Saturday afternoon at EASL (4/14/07).
* We expect VRTX to present SVR12 data from Arm 4 (12 wks of VX-950/PEGIFN/RBV; n<20). Vertex will focus on # of pts who completed tx as opposed to ITT in this arm who achieve SVR12. In their view, completers analysis is best surrogate for response. Pts in this arm are required to have an RVR @ wk 4 and maintain it through wk 12 to d/c tx. Otherwise, those who do not achieve and maintain RVR will cont on PEG-IFN/RBV and will not d/c therapy at wk 12.
* A relapse rate of 20% (what we see w/ PEG-IFN/RBV) or lower would serve as a strong indicator that 12 wks of triple tx is sufficicent. Conversely, a high relapse rate (50%+) would signal that longer durations of tx will be required.
* At EASL, we also expect VRTX to report EOT viral load reductions and 12 wk safety data for all arms.
www.smithbarney.com
You will have to register for access.
Frozen food alarm
http://www.news.com.au/sundayheraldsun/story/0,,21357807-2862,00.html#
Suellen Hinde, Health reporter
March 11, 2007 12:00am
WORLD-first Melbourne research has found that frozen food may be the cause of a dramatic rise in immune disorders in children.
The studies have revealed a bacteria that thrives in freezing temperatures is present in almost half of Victoria's cases of childhood chronic inflammatory bowel disease.
Experts at Murdoch Children's Research Institute and Royal Children's Hospital proved Mycobacterium avium paratuberculosis lives in the digestive system of almost half newly diagnosed cases of Crohn's Disease.
The microbial pathogen is also widely found in cattle. It is the first time it has been scientifically linked to childhood cases of Crohn's Disease.
MAP bacteria live in the soil and is one of four that thrive in minus 1C to minus 10C.
Of the more than 45,000 Australians diagnosed with the incurable disease, the youngest is only two.
The breakthrough discovery offers hope of relief to sufferers, who have difficulty eating because of pain and experience extreme weight loss, diarrhoea, fatigue and stunted growth.
Crohn's Disease has increased 20-fold in Victoria in the past 30 years. At least 70 childhood cases are diagnosed each year in Victoria.
"The worldwide increase in Crohn's Disease far exceeds anything that can be explained by a genetic predisposition alone," RCH head of gastroenterology Dr Tony Catto-Smith said.
Dr Catto-Smith said the research team studied MAP because cattle suffered a similar inflammatory disease with the same microscopic features caused by the bacteria.
"We know the bug is present in our environment," he said. "And 41 of the 100 CD cases have the bug present in blood and biopsy suggests some form of association.
"Whether this bacteria is the trigger is unknown, though."
Dr Catto-Smith said the researchers were working on a theory that much of the food we eat had been refrigerated between being produced and when eaten".
"Refrigeration has been effective in preserving food, but all food in the fridge will eventually go off -- certain organisms like cold and can grow and flourish there," he said.
Sorry , I just missed posting this before your reply. See Dew's post for the interaction trial design :
http://www.investorshub.com/boards/read_msg.asp?message_id=13614225
The enrollment has been upped to 117 , I believe. I'm not aware of any other modifications.
I wonder , too , about the authenticity of some patient forum posts but I'd guess that the bulk of them are for real.
I'm pretty sure the patient in the forum must be in one of the arms of the interaction study. The follow-up SOC , while not specified in the trial design , is probably offered to all HCV trial partipants for ethical reasons and/or as an incentive to enroll.
I would presume IDIX has plans to follow the interaction study patients to determine SVR rates , and suspect that they've done so for all previously treated patients as well , in spite of the lack of reported data to that effect.
Patient forum discussion of NM283
http://www.medhelp.org/forums/hepatitis/messages/45352.html
OT : SCLN
I'll be interested to see if SCLN targets HCV with their new candidate , SCV-07. Dose optimization studies are supposed to start in Q2. Since the field is still wide open for an immunomodulator to replace ifn , it probably makes sense to go after HCV but I'm sure many SCLN investors would think : " Oh NO ! Not again ! "
:)
Agreed. I wonder about the eventual impact on clinical trials in gen 1 patients. If the data is clear that some patients do equally well with 24 wks. versus 48 wks. of tx. it would be unethical to treat them for the longer period , given the AEs associated with tx.
For the time being they can solve the problem by excluding pts. with low viral load but as the predictive algorithms improve it may require mid-stream tx. decisions based on viral load measurements thus complicating trial design , enrollments , etc.
PEGASYS(R) Gets European Approval for a Shorter Treatment Duration for Some Genotype 1 and 4 Hepatitis C Patients who Show a Rapid Response to Therapy
http://www.prnewswire.co.uk/cgi/news/release?id=192225
BASEL, Switzerland, March 6 /PRNewswire/ --
- Shorter, Simplified Treatment Option May Encourage More Patients to Seek Treatment
Some hepatitis C patients with difficult-to-treat HCV genotype 1 who respond quickly to treatment with a combination of PEGASYS(R) (pegylated interferon alfa-2a (40KD)) plus COPEGUS(R) (ribavirin) can benefit from a shorter and simplified course of therapy, following Thursday's Commission decision. With the new approval, a subset of patients with genotypes 1 and 4 HCV who achieve rapid viral response can now receive a shortened, 24-week duration of treatment with Roche's PEGASYS plus COPEGUS. This is half the normal treatment duration.
Shorter, Simplified Treatment Shows Excellent Chance for a Cure
The EU approval is based on data from two pivotal clinical trials for PEGASYS plus COPEGUS.(1,2) Results from these trials show that among patients who achieved a rapid viral response (undetectable viral load at week 4) in the first month of treatment up to 93 per cent of patients with genotype 1 HCV with a low pre-treatment viral load and 83 per cent of patients with genotype 4 were cured following only 24 weeks of therapy - a similar cure rate to that seen following 48 weeks of therapy.(3)
"This is excellent news for patients with hepatitis C," said Dr Peter Ferenci, Professor of the Department of Internal Medicine IV, Gastroenterology and Hepatology, at the University of Vienna, Austria. "This means that patients can find out within one month of starting therapy if they have an excellent chance of being cured and can benefit from a shortened treatment duration. This is likely to encourage patients to seek treatment and motivate them to stay on therapy."
New Recommendations for Treatment
A shorter, 24-week course with PEGASYS plus COPEGUS is now an option for the following patients:(4)
- Genotype 1 HCV with a low pre-treatment viral load (defined as <800,000 IU/mL) and an undetectable viral load at weeks 4 and 24;
- Genotype 4 HCV regardless of pre-treatment viral load and an undetectable viral load at weeks 4 and 24.
"This licence change reflects Roche's commitment to finding better treatment solutions for patients with HCV by improving treatment with existing therapies and developing new medicines to treat hepatitis C," said Claire Steers, PEGASYS Lifecycle Leader at Roche in Basel, Switzerland. "Roche is committed to finding solutions for a broad range of hepatitis C patients by continuing to simplify treatment with PEGASYS."
APASL 3/27-3/30/07
Some telbivudine stuff in presentations 062-069 , for example.
http://www.apasl2007kyoto.org/web-oral-session.htm