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Re : Ribavirin successors
I think Viramidine is still in the works but I doubt that it will offer major improvements to ribavirin.
The question about riba replacements becomes more interesting as the PI and polymerase candidates advance , since the reduced requirement for additional direct antiviral activity might provide new life to previously abandoned candidates. Could VRTX resurrect VX-497 ? Roche , I believe , looked at the L-isomer of riba a few years back , which would be an interesting combo for IDIX to explore if riba causes problems.
Cellcept, an IMPDH inhibitor like riba and VX-497 , is already on the market so there would be no delay or complications involved in using it as compared to another experimental compound , but I don't think the studies using it thus far have been very promising.
Re : o/t: we're now up to Hepatitis F or G... and counting
I'm glad they dispensed with the naming system they used to use for HCV , otherwise hepatitis F would be : non-A non-B non-C non-D non-E hepatitis. I just hope they don't end up using all the letters.
I'm not betting they won't , though. The article below describes the work of Drs. DeRisi and Ganem , who are the ones that found the virus associated with some prostate cancers. They have a microarray system that contains ~10,000 DNA fragments drawn from every virus in DNA databases , which can be used to identify any known or related viruses in human tissues and other specimens. By the time this sort of inventory is complete and correlated with disease , I suspect a lot of conditions that now have names beginning with "autoimmune" or "idiopathic" will get new handles.
Modern-day Virus Hunters
http://www.hhmi.org/bulletin/august2006/features/
>> There is a sizable rate of new HCV infections yearly in the U.S. and E.U. but I believe it is much lower than at the peak , and should decline further with better education and preventative measures. <<<
Looks like I spoke too soon on that last part:
Hepatitis C rises among young people
Mass. officials suspect jump tied to drug use
By Stephen Smith, Globe Staff | May 8, 2007
Hepatitis C infections among Massachusetts adolescents and young adults rose dramatically from 2001 to 2005, new data show, prompting health officials to warn doctors statewide to screen and educate patients about the blood-borne disease.
Confirmed and suspected cases of hepatitis C among 15- to 25-year-olds climbed from 254 in 2001 to at least 784 in 2005, the state Department of Public Health found. In Boston, about 100 cases of the potentially painful and life-threatening liver infection were reported in 2006 -- the most this decade.
Massachusetts is better at tracking infectious diseases than many other states, making it difficult to compare state data with nationwide trends.
The spike in hepatitis C, an illness most often spread by drug needles tainted with the virus, emerges during a period of epidemic heroin use in Massachusetts.
That is almost certainly no coincidence, said John Auerbach , the state's public health commissioner. "I suspect there is a direct correlation between the increase in hepatitis C among younger people and the increase in injection drug use and heroin use, in particular," Auerbach said. "It is terribly tragic, but it is very consistent with the pattern of risk that goes along with injection-drug use."
..
and:
Dr. Maureen Jonas , a pediatric liver specialist at Children's Hospital Boston , regularly witnesses the consequences of that behavior.
"I am seeing, sadly, a fair number of 13-, 14-, 15-, 16-year-olds with IV drug use and hepatitis C," Jonas said. "A lot of them -- not all of them -- knew that the person whose needle they shared had hepatitis of some sort. ( !! )
Full article at :
http://www.boston.com/news/local/articles/2007/05/08/hepatitis_c_rises_among_young_people/?page=1
or :
http://tinyurl.com/ywggj8
>> if those trials where to fail on those primary endpoints, and the trial is followed and later shows a significant increase in extending the lives of the patients taking the drug, why wouldn't the FDA accept that data and approve the drug? <<
They would love to do that , I believe. The problem is , there's nothing in their rule books to cover that situation , and bureaucrats insist on covering their "situations".
>> The benefit of ribavirin may not be all that complicated. Riba's main contribution is probably that it works well against mutant strains while NM283 works mostly against wild-type HCV. <<
If the only benefit of riba is on direct antiviral activity , that may be true. However , it seems to be widely acknowledged that riba reduces relapse rates , at least as regards usage in combo with ifn. That implies that if you look at two groups of patients , one group treated with ifn and the other with ifn/riba , and in which all patients become HCV-negative at week X and remain HCV-negative Y weeks until EOT , you will see a higher SVR rate in the combo group. Assuming this is true , this further implies an effect beyond one on direct antiviral activity. One MOA that has been proposed for this is the tendency of riba-treated patients to show a Th1-biased immune response as opposed to a less effective Th2-type response.
JP sort of hinted at this in the webcast while talking about the "magic" of ribavirin , when he lamented that although many patients in the nonresponder trial were HCV-neg for six months or more , none achieved SVR. I think it's possible that he and others at IDIX may have been truly surprised by this , but I question whether they should have been.
>> The "creative approach" is quadruple therapy for partial responders to first-line SoC. I think this is clear from the MS webcast. <<
I didn't pick up on that but you're probably right.
Not quite as 'creative' as I had hoped but if they can make it happen I'll live with it.
I think the HCV replicon assay does have some serious limitations , but it also has a decent record of predicting in vivo results so it's been widely used to screen preclinical candidates. Newer models , including an infectious cell-culture system where the cells actually produce complete virions that can infect new cells ( or chimps ) , and one using immune-deficient mice with humanized livers , will probably overcome some of the limitations of the replicon assay. Still , they're just models. If the 283/riba interaction paper had been about studies in chimps , it would probably be 'game over' , but since the replicon assay was used we still have some reason to be hopeful.
Also , as we've discussed before , there may be workarounds to a 283-riba interaction. If a triple combo of 283/PI/ifn had potent antiviral activity , e.g. achieving HCV-negativity in a week or so and maintaining it for 10-12 wks. , you might be able to follow that with a triple of PI/ifn/riba , or just ifn/riba , to consolidate the immune response and allow SVR. It wouldn't really be too much different from what VRTX will be doing with their 12 plus 12 approach. It all boils down to whether riba is critical in that first stage of treatment.
A negative interaction study would likely put IDIX in a weak negotiating position on 283/PI combo approaches , since IDIX would need the PI more than the other company would need 283.
OTOH , IDIX could surprise us with that " creative approach " they've been hiding from us. ;)
Re : handicapping drug interaction study
Let's hope it's not " handicapping " to future prospects for NM283. :)
The thing that frustrates me when reviewing the paper on the 283/riba interaction is the experiment they didn't do -- an interaction study comparing ifn/riba to nm283/ifn/riba.
The real 'magic' of riba in HCV is only revealed in combo with ifn. As monotherapy , riba is almost useless vs. HCV , in vitro or in vivo. Combine with ifn and you get a synergy in direct antiviral effect in vitro or in humans , and also the reduction in relapse rates in human studies. So , I agree with you that the riba/283 interaction paper points more toward a negative interaction on 283 antiviral activity , as opposed to one on riba direct antiviral activity , and it tells us nothing about how 283 might effect the 'magic' of the ifn/riba combo. It might have a positive , negative , or no effect , and human studies are the only way to get the full contribution of the immune effects , as you said. ( though innate immune effects , like ifn pathway effectors , can influence replicon antiviral results )
I think the upside on IDIX share price if the interaction study looks good is much greater than the downside if it looks bad. I'd place a bet here based on that imbalance , except for the gut feeling that tells me that the results will be problematic. I disagree with Dew that the decision to delay looking at combos with riba was just a gamble that didn't pay off. The 'magic' of the ifn/riba combo was well known when they started trials on 283. I think the decision was more likely based on replicon and maybe other studies that suggested it was not likely to be a fruitful exercise. It may have been NVS folks or others besides JP at IDIX who influenced that decision , but as CEO of IDIX , JP is the one who will bear the brunt of the blame if it turns out to have been a bad decision. In the recent webcast , he was careful to point out that riba combos will be studied immediately with the 2nd-gen candidate. " I ain't gonna go thru this mess again ! " **
** Not a direct quote. :)
re: Quiz .. Dang ! I can't put my finger on it but I remember seeing it somewhere. It wasn't Fauci. This guy is way more high-powered than Fauci.
I'll get it , eventually.
>>> You're statements were vague enough that I'm not quite sure what you mean by 10 mths more survival 80% <<<
You're right , it was a poorly constructed example. I was trying to present a choice in a simple way that might be the way it would be explained to patients , without getting into statistical detail.
My point was only to say that many terminal patients might look more favorably on treatments that showed a larger average effect size , though with more variability , smaller trials , etc. , and thus a higher probability that they were due to chance , than on treatments that showed a small effect size but with a high reliability that the effect is real , if this treatment choice could be explained to them in easily understood terms. Something like a toteboard at the racetrack , showing continuously updated odds and payoffs , might be useful. ;)
PGS said that docs will often disregard other studies if they have doubts about them , in favor of treatment strategies they have confidence in and are more familiar with. The current flood of support from patient groups in favor of Provenge approval is evidence that patients often have their own ideas about such things , and it seems their ideas are at odds with at least a few of those docs , and more than a few of the statistical purists.
>>> docs are reluctant to experiment on their patients by abandoning their effective treatment strategies for the latest small trial that showed a benefit. <<<
I have no doubt you're correct about that , but my sense is that cancer patients might come to a different conclusion than their docs , given all the information and the opportunity to weigh in.
For example , given a choice of the following two treatments , identical in all ways except presumed treatment effect and statistical robustness supporting that effect , I'm convinced that many docs and all statisticians would choose #1 , while most patients and other sane people would choose #2 :
#1 ) 2 months of increased survival with a 99.999% probability.
#2 ) 10 months of increased survival with an 80% probablility.
Investors , while not known for their sanity , would also choose # 2 , since it represents a "probable present value" of 8 months compared to only 2 months for #1.
>>> One thing InterMune had mentioned in the past (again beyond my HCV knowledge to agree with or refute) was that they were of the belief that the virus in the serum was not significant and in fact could not be inhibited with antiviral therapy and didn't even contain the NS3 protease. <<<
As a rule , I'm suspicious of companies that make this type of statement at presentations. By that I mean saying something that is technically true if parsed word-by-word , but is misleading as it will be understood by most listeners.
The statement is true with the word "serum" ( or "plasma" ) and false with the word "blood".
HCV needs to be in a cell to produce the polyprotein that contains the protease , and serum is cell-free. Lymphocytes circulating in the blood are known to support replication , however , as well as other extrahepatic tissues. Companies that have spent years developing a highly liver-targeted drug may be inclined to discount these facts , which have only become known relatively recently , since they don't fit well into the compelling story they've been pitching to investors for so long.
ITMN's increased fondness for elevated plasma levels of 191 might signal a gradual shift in the sales pitch so as to make it fit better with the evolving science.
Re : in vitro study
JP sounds pretty confident about not expecting to see any interaction as to pK data , but I don't think he's too sure about effects on antiviral activity. He made a comment on the Morgan Stanley call to the effect : " We don't know what kind of magic ribavirin does , but we know it does some kind of magic. " If that's the case, it would be kind of hard to predict whether NM283 would add or subtract from the magic.
I feel for JP in a way , because he's in a bit of a lose-lose situation as regards the interaction study. He loses if there is a negative impact on antiviral activity , as that could wreck NM283 development , even for combo studies if riba is part of the combo. If the interaction study turns out well , he loses because it reminds everyone what a boob he was not to include triple-therapy studies in the plan from the beginning.
The failure to do these studies earlier is what makes me most pessimistic about the outcome. I just find it hard to believe they would have waited till this late date to try triple therapy unless they had a bad feeling about the outcome. Current share price probably reflects a similar expectation by others , so the upside could be considerable in the event of favorable results.
Re : ITMN
I haven't listened to any ITMN calls lately , but I plan to so I might say more later.
I suspect the comments relating to plasma levels meant they thought that food helped maintain effective drug concentrations by modulating absortion and metabolism. They're probably not as interested in having a totally liver-targeted drug now anyway , since it's now known that there are many extra-hepatic reservoirs of HCV. Remember Viramidine.
I wouldn't worry about the rash since VRTX doesn't seem to. It might be a marker of activity , for all we know.
I think you can count on the need for ifn/riba like VRTX and everyone else , for a while at least.
I'd bet that ITMN tries to match steps , though a couple behind , with VRTX in just about every way. Getting to P3 before VX950 is SOC would be good if they can manage it. Even if not , they'd probably be better off doing a non-inferiority vs. 950 in naives rather than tackling nonresponders first. ITMN is far enough behind VRTX , like S-P , that going straight to combo with a polymerase inhibitor might be the best path. I'm sure JP at IDIX would be happy to talk. ;)
>> There is a good reason why scientists want something to occur with 90%+ certainty rather than, say, 67% certainty... the latter threshold would basically ensure that progress slows to a crawl. <<
Most scientists would also agree that progress would slow to a crawl if every experiment had to reach 99.999% certainty , because costs , time , and manpower requirements would be prohibitive. There has to be some judgement used , depending on circumstances.
Consider an analogy between drug approvals and skydiving , at two extremes.
Anyone looking to buy a parachute for sport skydiving ( for fun , not because he has a death wish ! ) would expect that parachute to have a near zero chance of failure of the main chute and a near zero chance of failure of the emergency chute. Combined , the overall chance of failure is essentially zero for a properly packed chute and the expectation of this is perfectly reasonable and prudent. This is analogous to the approval standards that should be required to approve a drug to grow peach fuzz on bald men's heads , for example. There should be two , independent , sizable , multi-center , placebo-controlled trials that hit a p <.05 , for a combined false-positive probability of 1/1600 , or less when you consider supporting earlier studies. This is also perfectly reasonable , IMO.
Now , at the other extreme , consider the 'skydiver' who launched himself off of one of the burning WTC towers on 9/11 , grasping a sheet of plywood in hopes of gliding to safety. He probably knew the odds of success were near zero. He would have preferred a reliable parachute , or for that matter an unreliable parachute , or maybe even a sturdy beach umbrella , but the plywood is what he had access to and he felt it gave him some incremental, greater-than-zero chance of surviving , so he gave it a try , understandably. This is analogous to patients with grim , late-stage cancers. They'd like to have a reliable , 1/1600 false-positive-type drug to try , but if there are none , they want the 1/200 type , or the 1/10 type , if that's the best available.
I'm all for standards , and for the need to do good science. I'm also for taking a big-picture approach when it comes to the approval of drugs for deadly diseases where there are currently no effective treatments. There is a greater-good principle involved , IMO , that says it's OK to have an approval process that allows one ineffective drug to be used for a few years before it's recalled , if that same process results in 5 , 10 , or 20 drugs that do provide benefit to get on the market for the extra few years required to conclusively demonstrate that benefit. This , I believe , was the thinking that resulted in subpart H approvals. The failure was in not extending the logic to cover situations like Provenge , which don't involve surrogates.
>> your question was obviously biased towards the patient welfare proponent.
I think both sides are necessary, but the con side is usually more well thought out IMHO <<
My question was biased towards the unpaid proponent , because that is the gist of the point I was making. I have my own problems with Abigail Alliance positions which , while noble , are unworkable.
The reason the con side is more well thought out in this sort of situation is that the con side is extremely well-financed. That's the problem , IMO. Money buys "facts" just like it buys votes. If big pharma can put every thought leader in any given field in their back pocket , what chance do we have of hearing "well thought out" arguments of both sides of a drug approval issue ? Zero.
Bought and paid for "professional proponents" can do much more damage over the long haul than the likes of Walker because they present better arguments , have superior credentials , etc. That's the definition of pernicious propaganda , IMO.
>>> Walker’s bias is the most pernicious kind <<<
This would be a good topic for a BV quiz. For example :
Consider the following two proponents of opposite sides of a hypothetical argument concerning drug development :
Proponent #1 , arguing the 'Pro' position -- His bias is based solely on his sincere beliefs and his concern for patient welfare , in fact , it is his raison d’etre. He has no financial conflicts of any kind.
Proponent #2 , arguing the 'Con' position -- His bias is based on the fact that the interests favoring the 'Con' position were the highest bidders for his services. He'd be happy to argue 'Pro' , if the price is right.
Question : Considering the welfare of society as a whole , rather than specific interest groups , which of the two proponents above would you consider more "pernicious".
>> Mr. Walker’s write-up in the WSJ is a highly biased view of the FDA, in my opinion. <<
Leaving aside the issue of the validity of Walker's arguments , I find it refreshing to see an opinion piece on drug development in the WSJ by an author whose disclosure statement reads as follows :
"Mr. Walker is co-founder and chief adviser for the Abigail Alliance for Better Access to Developmental Drugs . He receives no compensation for his work as an advocate, nor has he ever received compensation from any private or public-sector entity involved in drug development, approval or marketing."
It sounds like Mr.Walker's bias is based on his concern for patients , and little else.
I wish the same sort of disclosures were common for physician FDA AC panel members. Instead we get COI waiver documents that assure us that the panel member is not biased by the grant money they receive from [DELETED] and the speaking fees they receive from [DELETED].
I'll take Walker's brand of bias any day.
Re : VRTX CC
>>> additional I thought interesting was when asked if 950 would be the leading HCV therapy 10 years from now (or something to that effect) the answer was no. <<<
I thought that was a pretty candid statement when I first heard it but I think it just reflects the likely evolution of the HCV market post-launch of 950 . Combos being the wave of the future , and with so many candidates in the wings , means that market fragmentation will diminish the importance of any one drug.
If I recall correctly , he also hinted at the importance of getting to market quickly. HCV in the major markets is a "bubble". If 950 is widely adopted , and especially if it's effective in nonresponders , VRTX could capture a major chunk of the then-current HCV market in the first 5 years or so post-approval , leaving scraps ( relatively speaking ) to be picked over by the rest. There is a sizable rate of new HCV infections yearly in the U.S. and E.U. but I believe it is much lower than at the peak , and should decline further with better education and preventative measures.
Re : VRTX
The Morgan Stanley call was a good one. Thanks for the tip. Though it was the CFO presenting , I believe , the coverage was excellent on the VX950 results , trials , etc.
The Deutsche Bank VRTX call today , by comparison , was a waste of time. Most of the questions asked by the moderator were incomprehensible and the others were inane.
A couple comments on the MS call :
* It was the first time I've heard VRTX be so explicit about avoiding anything that might endanger the VX950 development pathway , in respect to combination trials with other direct antivirals. It's clear to me that they won't initiate any combo trials in humans until 950 is approved or , alternatively , the FDA somehow guarantees that combo data won't impact 950 monotherapy approval , which seems very unlikely. I suppose SGP might be more open to the idea of comboing their PI as a way to leapfrog VRTX.
* Somewhat in contradiction to the above , he said that VRTX would establish a "footprint" in combo therapy in 2007. My interpretation is that he means animal feet , not human.
* The P3 will almost certainly contain a 12 plus 12 VX950 arm , i.e. 12 wks. triple therapy followed by 12 wks. SOC.
* The choice of primary endpoint in the 950 P3 is up in the air until talks with the FDA are completed , but one possibility suggested was comparing 950 24-wk. SVR to SOC 48-wk.(EOT) PCR-negativity. The bottom line is that this P3 may not look like the ones we've seen before.
* VRTX is looking at the possibility that something less than 12 wks. of triple therapy may be required for optimum results , followed by a period of SOC , at least in naives. They may even add an arm in the P3 to sort this out. The CFO expressed the concern that they would not want to find this out after VRTX was on the market ( and priced based on an assumption of a full 12 wk. regimen ).
* It seems the rash problem pops up around 9 wks. into VX950 tx. , on average. If they can shorten the treatment time , they may be able to stop 950 just about when the bulk of patients would begin having problems , or just after they've started getting the rash. The question nobody ever asks but one I'm eager to hear addressed is : Does rash signal immune-breakthrough , i.e. reversal of tolerance , and thus provide a marker for when the viral suppression is all immune-mediated and thus only ifn/riba is required thereafter for the consolidation phase and eventual SVR ? It sure sounds like that's what's happening to me.
FWIWFAIK
Re : High Calcium, Vitamin D Intake
Unless brain lesions are inversely associated with cognitive impairment , this study is directly contradictory to the one from Duke. This one suggests that at least one dairy product , cheese , along with bread and cereal are protective against cognitive impairment :
1: J Nutr Health Aging. 2007 Jan-Feb;11(1):49-54.
Dietary factors and cognitive impairment in community-dwelling elderly.
Rahman A, Sawyer Baker P, Allman RM, Zamrini E.
Department of Neurology, School of Medicine, University of Alabama at BBirmingham, USA.
BACKGROUND: Diet may play a role in cognitive impairment. OBJECTIVE: To examine the relationship between dietary factors and cognitive impairment. DESIGN AND METHODS: All subjects (n=1056) were participants in the State-wide Survey of Alabama's Elderly (1986-87). Basic demographic information, Mental Status Questionnaire (MSQ) score, and dietary intake frequency of meat (pork, beef, lamb), fish, chicken or turkey, vegetables, fruit, milk, cheese, desserts, bread or cereal, and dried beans and peas were ascertained during an inhome interview. RESULTS: Most participants were female (67%) and white (73%) with a mean age of 69 years (SD 8.9, min 55 max 94) and mean years of education of 10.7 (SD 3.8, min 1 max 18). Intake of cheese was found to be inversely associated with cognitive impairment in a simple logistic regression analysis, (OR = 0.59; 95% CI: 0.42, 0.84; p=0.003) and in a multiple logistic regression analysis (OR=0.68; 95% CI: 0.47, 0.99; p=0.04), after adjusting for basic socio-demographic factors and for other dietary factors. Increased frequency of cheese intake was associated with decreased cognitive impairment (p=0.0034). In the multiple logistic regression analysis bread or cereal (OR= 0.37, 95% CI: 0.14, 0.97; p=0.044) was inversely associated with, and dessert intake (OR= 1.70, 95% CI: 1.12, 2.59; p=0.013) positively associated with cognitive impairment. Conclusion: Dietary intake of cheese is associated with a lower prevalence of cognitive impairment, with a dose-response effect, while intake of dessert is associated with a higher prevalence of cognitive impairment. Possible reasons for a potential protective effect of cheese ingestion are discussed.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&...
Re: High Calcium, Vitamin D
They say just enough to get everyone worried , and more than enough , IMO , to show they don't have a clue what the true cause is.
This is from another report :
"In earlier studies, Dr. Payne's team had found that individuals who consumed more high-fat dairy products had more brain lesions than those who did not follow such a diet but that fat intake in general was not a significant factor. If not the fat, the researchers asked, what was it about a high fat dairy diet that accounts for the positive correlation with brain lesions? This new study points the finger to a prominent component of dairy - namely calcium - and the Vitamin D that is found in many dairy products and vitamin D-fortified foods."
http://www.sciencedaily.com/releases/2007/05/070501115230.htm
Given all the crap -- hormones , antibiotics , maybe a little melamine -- in dairy products , to look only at fat , calcium , and vitamin D as possible culprits shows a real lack of imagination , but it appears to me that's what they've done. There is no indication that they made an attempt to distinguish between the effects of different sources of calcium and vit D ( food vs. supplements , sunlight for vit D , etc. ) , which I would want to see before placing the blame so precisely.
Re : GNVC / Garren
>>> he notes that pancreatic cancers are quite tough and fibrotic and would require multiple injections <<<
In data presented to date , it appears that there's no measurable efficacy difference between delivering the full dose of TNFerade in a single needle pass by PTA , or in multiple passes using EUS. This was examined in the dose-escalation study , though with only about 20-25 patients per arm ( EUS / PTA ). See slides 20 , 22 , and 25 in this pdf :
http://www.genvec.com/download/DDW%20pancan.pdf
It will be interesting to see if this holds true as we see more data. If so , it means that the vector , the TNF , downstream effectors of TNF , or some combo of these diffuse sufficiently thru the tumor from a single needle tract to effect a response equivalent to that from multiple passes.
>> How are they going to be able to sell this in the US or elsewhere without an approval path?...and Rituxan is on patent until 2013 <<
It sounds like Reddy will go thru the whole clinical trial process in the U.S. and expects to be ready when the drug goes off-patent in 2013. In the meantime , they may be able to sell their drug in India and other countries with poor IP protection and regulatory practices.
I'm sure Roche would be all over them in the U.S. or E.U. if they tried to jump the gun on patents.
Re : Patent ‘Obviousness’
>>This is an excellent ruling that was long overdue, IMHO.<<
Agreed. Is there now a basis for challenge of patents on isomer drugs like Lexapro , which is a pretty obvious improvement of Celexa ?
Hopefully this ruling will spur some real innovation and decrease the amount of research dollars wasted on me-too drugs.
Melamine in big demand in China as a food additive
( I wonder if "gluten sensitivity" in humans is really " melamine sensitivity ". )
http://www.washingtonpost.com/wp-dyn/content/article/2007/04/30/AR2007043000301.html
By Niu Shuping and Lucy Hornby
Reuters
Monday, April 30, 2007; 6:42 AM
BEIJING (Reuters) - Melamine is so popular as a protein lookalike feed additive that at least one Chinese manufacturer is believed to have torn down buildings to get to leftover scraps, industry officials said on Monday.
Melamine, used in making plastic and fertilizers, was blamed for killing pets in the United States and South America last month after it was found in wheat gluten and rice protein exported from China for use in pet food.
More than 100 brands of pet food were recalled, triggering a round of finger-pointing among pet food suppliers in the U.S. China last week said it would ban melamine-tainted protein products from export and from domestic markets.
Melamine scrap is believed to be commonly mixed in animal feed in China to artificially boost the protein level, especially in soymeal, tricking feedlots and farmers into paying more for feed for chickens and pigs.
"The chemical plant next to us used the melamine scrap as waste for landfill and built houses on it. Then they tore down the buildings to get the scrap once the price rose," said a manager with Tai'an Yongfeng Feedmill Co. Ltd in the coastal province of Shandong.
"It is a very popular business here. I know people have been mixing this since 1991."
CUTTING CORNERS
Shandong is the centre of China's poultry industry, which is undergoing an industrial revolution as a wealthier population demands more meat and poultry.
The industry has switched away from farmers raising a few chickens in backyards for sale in covered markets, to packed henhouses of thousands of birds that are slaughtered for national distribution.
Thin margins mean the temptation to cut corners is strong, especially for middlemen selling soymeal in bulk to small feedlots.
"For every percent of protein you gain, you can make 55 yuan. So if you can turn 38 percent protein soymeal into 43 percent meal, you can make more than 200 yuan per ton," said the manager.
"Feed mills usually have poor equipment and they cannot detect the chemical through tests, not even the big mills."
"Fake" soymeal products were widely sold in Hebei and Shandong provinces, the manager said.
"I never heard of this stuff. But in general, chemical products shouldn't be put in animal feed, that's very dangerous," said Xie Hong, executive vice president of Sichuan Southhope Industry Co., China's biggest feed producer and controlling stakeholder in Liuhe Group, the country's largest poultry producer based in Shandong.
Beijing has issued no regulations to ban the use of the chemical in feed, said a China Feed Industry Association official. He denied any knowledge of use of the additive in feed.
But an official at the Shandong Mingshui Great Chemical Group, which produces urea for fertilizer, said all of its melamine scrap was sold to companies to boost the nitrogen content in their feed products.
"They add very small amount of melamine scrap to the feed, which does not lead to mass deaths of animals. But a few here and there might react," said the manager at the Shandong feedmill, who had not heard that the product had been linked to pet deaths overseas.
"It might be another story for pets though."
Re : CC
Just got around to listening to the call. I agree that the tone was more balanced than in some previous calls ,i.e. not too hot , not too cold.
JP's answer to a question at the end was curious , I thought. Someone asked about the frequency of rash in the interaction study and whether it was consistent with what is expected with SOC , and JP said : " We haven't seen any ribavirin rash in our study " , or something to that effect.
Since most patients are past 8 wks. by now , I'd expect that some rash would be showing up. If rash is reduced in the NM283 arm it could be a sign of a drug-drug interaction. Still , the SOC patients should show the normal frequency of rash. I wish the questioner ( Kolbert , I think ) had pursued it further.
Although they set the bar at a 10% improvement in PCR-negativity at 12wks. ( vs. SOC ) as a minimum to pursue a P3 testing triple therapy vs. SOC , I think JP also implied that they might not go that route even if they meet that threshold , and instead might focus on other paths to approval , like combos with other investigational agents.
It sounds like they expect the next 3 months to be more representative of Tyzeka uptake than the sales data to date , since they're just now rolling out a more comprehensive promotional package. So keep an eye on those sales data , go_seek ! ;)
At $7.00 it's hard to make a case for selling IDIX but I don't think I'll buy more now , either. The interaction data in June will probably move share price a fair amount , assuming the results haven't leaked by then , or have already.
Re : Onconome - new prostate cancer marker
Maybe DNDN should license the EPCA peptide for a 2nd-gen Provenge. It sounds like EPCA is more specific and universal in PCA than other markers.
>>>Can't get past the image of a very short man with pointy ears and a funny hat poking around near my prostate. <<<
Whatever floats your boat !
:)
Identical , or nearly so , ADME values so that dosing remains the same? And the actual drug is identical -- just a different delivery system.
Re : Quiz
I suppose they could simply stop making the XR , leaving patients with the choice of Vyvanse or immediate-release forms.
Presumably those who preferred the XR would go with Vyvanse , and it would be some time before the generic XR was available and by then they'd be unlikely to switch back.
...I think Roche and S-P still have nightmares about VX-950 and would love to see it go down in flames.
>> This is unduly histrionic, IMO. <<
I agree. I'll rephrase :
I think Roche and S-P would rather not think about VX-950 because when they do , those thoughts are , to a certain degree , possibly , rather unpleasant and thus they might not be unduly disturbed if VRTX were to stumble somewhat whilst traversing the VX-950 development pathway.
Yeah , that's much better.
Thanks.
>> If VX-950 allows the SoC to be shortened from 48 weeks to 24 weeks, the motivation for people infected with HCV to seek and complete treatment will be greatly increased, which will cause more doses of all brands of ifn to be administered. It’s not unreasonable to think that a shortened SoC could increase the number of treated patients by as much as the 2x reduction in treatment time. <<<
There probably will be a surge in patients seeking tx. for the first time because of the shorter duration , at least for a while , but I think Roche and S-P still have nightmares about VX-950 and would love to see it go down in flames.
Looking at an individual patient who achieves SVR , cutting the tx. duration from 48 to 24 wks. cuts the requirement for ifn in half. Those currently achieving SVR with 24 wks. may only require 12 or 16 wks. Those losses to the ifn companies are indisputable.
The untreated and nonresponder patient pools have been like buried treasure for Roche and S-P , as they've known that eventually most of them would get treated or retreated using some regimen containing ifn , and for the longer tx. durations.
Now they have to worry that VX-950 will achieve higher SVR rates on naives , thus reducing the incremental addition to the nonresponder pool , and also that many nonresponders may be cured with only 24 wks. of VX , instead of 48 or 72 wks. ( or multiples of that with continued retreatment ).
The nightmare intensifies when they start to think about ifn-less combo therapies , as that market will likely be carved up among a number of players as it evolves.
Short-term , the picture might even look rosy for ifns after VX approval , but I think any analysis that looks beyond a few yrs. post-VX will show declining revenues relative to current projections , and maybe even in absolute terms.
I was expecting something new. Thalidomide is old news. I can't search here but I bet if someone searches our old threads on the " creative approach " for IDIX in HCV nonresponders , you'll find we mentioned thalidomide as a possibility.
EDIT : OK , Corlux is new , but not nearly as well known or controversial as thalidomide.
Me and Biowatch get full credit , dammit !
Duh- thalidomide
Quiz : Crestor
Re : HCV quiz
I think there are probably a handful of drugs that qualify , but my guess is you're thinking of the diabetes drugs like metformin and Actos.
Re : MATK
One thing about MATK -- you can't say they suffer from ADD. It's been almost all DHA , all the time , for 20 yrs. or so.
That's been my main complaint about them - they're boring.
There must be a cancer cure or two floating around in those vats of microalgae.
re : Cipan
These bogus PRs seem to pop up every year. See this from last May :
http://www.telecentro.pt/forum/ler_questao.asp?qt=203&varid=3
"Lisbon - A source from Sonae SGPS said today that Sonae SGPS will launch a takeover to Combimatrix Corporation.This source was the same that said that Sonae SGPS will takeover SCICLONE PHARM (SCLN).
Sonae SGPS, will notifie next friday the Portuguese National Securities Market Commission (CNMV) that it was willing to waive the condition of a 75% minimum acceptance level to which its public offer for the acquisition of Combimatrix Corporation shares was subject, taking into consideration that the response received will be sufficient to develop the business project pursued through the takeover bid.
Sonae SGPS will launch a takeover bid for Combimatrix Corporation with the payment of $3.50 USD for each of the that responded to the tender offer, this initial offer could reach the limit of price of $4.15 USD for each share of the company."
etc., etc...
>>> yet the hypothetical scenario may illustrate the pitfalls of allowing the FDA to approve drugs with too low a hurdle. <<<
I accept your argument if you accept that it means that no drugs should ever be approved on the basis of surrogate markers , the ultimate " low hurdle " .
You , and the FDA , can't have it both ways , IMO.