Doubts Build On Glaxo’s Antiaging Drugs
Posted by: drugsinus on: January 26, 2010
GlaxoSmithKline shocked the pharmaceutical industry in 2008 when it dropped $720 million to buy Sirtris Pharmaceuticals, a biotechnology company working on drugs based on resveratrol, a chemical in red wine thought to combat the effects of aging.
The drugs are thought to enhance the activity of SIRT1, a key enzyme involved with the aging process. Glaxo hopes the drugs will lead to myriad new treatments for diabetes, cancer and other diseases.
But now researchers at rival companies are openly questioning whether the compounds will work. They say they are unable to replicate key laboratory experiments backing the drugs’ promise.
In the latest salvo, Pfizer ( PFE – news – people ) researchers report in the January Journal of Biological Chemistry that neither resveratrol nor several other Sirtris drugs hit the SIRT1 enzyme at all. They suggest that Sirtris’ earlier findings to the contrary might be due to an experimental artifact. The Pfizer study follows on the heels of similar study last year from researchers at Amgen ( AMGN – news – people ).
In 2007 Sirtris made headlines when it reported that a compound called SRT1720 lowered blood sugar in diabetic mice. But when Pfizer researchers tried to repeat the experiment, they found that low doses of SRT1720 had no effect on blood sugar whatsoever–and the mice gained weight. High doses of the drug, meanwhile, killed three of eight mice, the Pfizer study says.
Sirtris has generated mountains of hype over the years. Its cofounder, Harvard biologist David Sinclair, had published studies showing evidence that large doses of the resveratrol chemical in red wine extends the lives of fat mice. Breathless press coverage has hinted that the compound, or its successors, could one day become life-extending pills for humans. Sirtris’ raison d’etre was to create more potent versions that could combat myriad diseases of aging.
The Pfizer scientists “have thrown down the gauntlet: They claim that the reported Sirtris compounds do not do what they are claimed to do,” pharmaceutical chemist Derek Lowe, wrote recently on his popular In The Pipeline blog. It is “almost certainly the case” that there are problems with the Sirtris compounds, he argues.
In an interview, Glaxo’s chief executive, Andrew Witty, says his company’s approach has always been “much more subtle” than “this very simplistic notion of this as a longevity pill.” He calls the dustup “a bit of a storm in a teacup” and says the drugs Pfizer tested in animals are not the same ones that Glaxo is currently testing in people as possible diabetes or cancer treatments.
“We’re not at all surprised that there’s some controversy,” says Witty. “Because there always is. People always have different opinions. Frankly, we didn’t think what was published was particularly comprehensive. We feel good about where we stand today.”
Witty says he’s comfortable with paying for high-risk research that may not always pan out. This focus on unpopular approaches has been a key part of Witty’s attempts to revive Glaxo’s research. Like those of every drug company, Glaxo’s labs have been relatively fallow for years. Already, the unpopular thinking has paid off. Wall Street expected a lupus drug Glaxo was developing with Human Genome Sciences ( HGSI – news – people ) to fail. Instead it is likely to be one of the biggest-selling new medicines launched this year.
Other risky bets include a drug that aims to prevent heart attacks by combating artery inflammation, and a partnership with Anacor, a San Francisco company that makes drugs based on a new type of chemistry involving the element boron. Witty says that researchers at Glaxo thought it was “completely mad” to do the Anacor deal.
“There’s no doubt there’s risk in pharmaceuticals, and there should be!” Witty says. “If you make 30% returns it should be a risky business. If you don’t want risk, go be a grocery store and make 6%.”
General Electric’s China Mammogram Move
Posted by: drugsinus on: January 22, 2010
Chinese women who can afford to queue up for a Mercedes or a Gucci bag are now coveting another high-end product: health care. Sales of ultrasound and other imaging machines to hospitals are “robust,” according to Chindex, a company that provides Western-style medical services in China.
So General Electric ( GE – news – people ) is participating in a $5 million program to do mammography screenings for 10,000 women a year in Sichuan Province, supplying its machines to three hospitals. Only 300 or so screening machines of all makes are in use now in China.
One problem: Just as new research has cast doubt on mammograms for middle-aged women in the U.S., some scientists say it especially makes no sense to encourage mass screenings in China. After reviewing past studies Hong Kong University professor Anthony Hedley and colleagues concluded in a 2002 paper that mass screenings in Asia aren’t worth the investment of time and money. Hedley says false positives are common because Chinese women’s breasts tend to be denser. These patients are immediately whisked off for further testing, much of it invasive.
Hedley says that 87% of suspect mammograms among Asian women are false positives and that if you screen 10,000 women in this population for a decade, you prevent 8 breast cancer fatalities but cause 13 complications from the treatments.
GE spokeswoman Christine Li says evidence shows that screening saves lives and added that many governments urge annual screenings.
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Industrial Chemicals Lurking In Your Bloodstream
Posted by: drugsinus on: January 22, 2010
Concern is heating up over whether common industrial chemicals found in plastics and other consumer goods could be harming our kids.
The Food and Drug Administration made headlines when it said last week that it would review the safety of Bisphenol A, an industrial chemical commonly used in plastic bottles and food containers. It is worried that the chemical might have subtle but deleterious effects on the neurological and reproductive development of kids.
For years the chemical has been the subject of controversy over whether it can harm people. Some studies have linked it to abnormal brain and reproductive organ development in animals while others have shown little evidence that is harmful in the small doses that are likely to be ingested by humans. Other adverse health effects to which it has been linked include erectile dysfunction and heart disease in humans and early onset of puberty in female rats.
But BPA is just one of hundreds of industrial chemicals that may be in your blood or urine right now. A report released by the Centers for Disease Control and Prevention in 2009 found detectable levels of a total of 212 chemicals in blood or urine samples from 2,400 people nationwide. These included the agricultural pesticide atrazine, the gas additive Methyl tert-butyl ether (MTBE) and the coal and petroleum byproduct benzene. Little is known about the human health effects of most of the chemicals.
The chemical industry has long argued that these chemicals are safe at current exposure levels. None have been conclusively shown to harm humans at low levels. But R. Thomas Zoeller, an endocrinologist and University of Massachusetts professor, says the widespread presence of industrial chemicals in the human population is alarming. “I sincerely hope that what we know from animal research doesn’t translate to humans, but I don’t have much optimism,” he says. Worse yet, he adds, “You’re not giving people a choice about contamination.”
Researchers are particularly nervous about the weed killer atrazine, BPA and other chemicals known as endocrine disruptors. These are thought to interfere with the body’s ability to regulate estrogen or other hormones. When those processes go awry, it can lead to neurological and reproductive defects. Endocrinologists are concerned that these chemicals may be able to cause subtle health problems at doses far lower than the high doses toxicologists typically use to assess safety today.
A widely cited study published in the Proceeding of the National Academy of Sciences in 2002 found that atrazine exposure at doses 30 times lower than allowed by the EPA caused tadpoles to develop both male and female sex characteristics, turning them into hermaphrodites. It also lowered testosterone levels in adult male frogs below the level found in females.
The EPA is evaluating the human health effects of atrazine and is expected to publish some of its results late this year. That’s not the only endocrine disrupting chemical that the EPA is worried about. Late last year, the agency quietly said that it would review the safety of phthalates, long-chain perfluorinated chemicals (PFCs), polybrominated diphenyl ethers (PBDEs) and short-chain chlorinated paraffins. The chemicals are found in a range of commercial and consumer products–building materials, semiconductors, furniture, toys and cosmetics–and tend to accumulate in the environment or in animal and human tissue. More than 1 million pounds of each is produced annually.
Cal Dooley, president and CEO of the industry group American Chemistry Council, says the industry has the “utmost confidence” in the safety of these chemicals and questions the EPA’s decision to single out a few chemicals.
U Mass’ Zoeller says the EPA’s decision to single out the four chemicals is sound, but he is also worried that outdated methods will be used during the EPA’s review. In the past, researchers have studied endocrine disruptors the same way they studied other potentially toxic chemicals: by giving animals ultra high doses and watching for toxic effects. But paradoxically, his research has shown that endocrine disruptors may cause the most harm at relatively low doses. Low doses of the chemical may mimic or disrupt the effects of natural hormones that have potent effects in small amounts. High doses, on the other hand, tend to desensitize the endocrine system, he says.
In addition to reviewing the safety of industrial chemicals, the EPA is also looking to reform decades-old toxic chemical legislation known as the Toxic Substances Control Act of 1976. Among its goals is to require manufacturers to release safety data, which they can currently protect as confidential information.
There are now 86,000 chemicals on the EPA’s inventory of compounds used in commercial and consumer products. Since 1976, the agency has only succeeded five times in restricting or banning chemicals.
“We feel that we need to be able to say with confidence that chemicals sold in the U.S. are safe,” says Jim Jones, deputy assistant administrator for the EPA’s office of pesticides and toxic substances. “We have a lot of work to do to get there.”
As for BPA, study results have been confusing as to whether or not it really harms people. Last week, for example, an epidemiology study in PLoS One found that people with high levels of BPA had a slightly increased risk of heart disease. A similar study conducted in 2008 by the same authors found a much stronger correlation.
During the Bush administration, the FDA deemed BPA safe at low levels. But citing new research on the chemical’s potential effects on neurological and reproductive organ development in infants and children, the FDA now says it will take steps to reduce BPA exposure in the food supply. Its BPA safety review won’t be finished until at least 2012, when two government studies on BPA are scheduled to finish.
What’s Next For Health Care Companies?
Posted by: drugsinus on: January 21, 2010
Does the election of Republican Scott Brown to the very Massachusetts Senate seat once held by health care reform’s standard-bearer, the late Edward Kennedy, doom the Democrats’ effort to change the way medical insurance works?
ObamaCare’s fate isn’t quite sealed yet. But Richard Evans, 47, a former Roche ( RHHBY.PK – news – people ) executive and Sanford C. Bernstein analyst who now runs Sector & Sovereign, a New York health care analysis boutique that tries to wring financial bets out of political headwinds, is bullish on health insurance stocks, like UnitedHealth ( UNH – news – people ), Aetna ( AET – news – people ) and WellCare. But he’s steering clear of drug makers like Pfizer ( PFE – news – people ) and Merck ( MRK – news – people ). (He recommends sub-sectors, not individual companies.)
The insurers are going to be boosted, he predicts, because of a longer flu season and because consumers are rushing to spend on health care in the fear that they might lose their jobs. Meanwhile, investors are underestimating the havoc that patent expirations are going to wreak on drug company margins.
Why listen to Evans? Back in November, as reform was passing the Senate and a victory seemed more likely, Evans issued a strongly worded note saying that the bill would fail. Many analysts at the time were recommending health insurers because there would be a relief rally when some bill finally passed.
“We no longer expect Congress to pass impactful health reform legislation this year, or even in this political cycle,” Evans wrote on Nov. 16. “Voter attitudes are shifting away from both Democrats and health reform; placing the considerable number of Dems from conservative states and districts in increasingly untenable positions.” He added: “For the time being, it’s simply over.”
Health care as a whole should continue to benefit, Evans says, because there is no way that a bill passes Congress now. Other people are arguing that the bill is doomed because Brown’s defeat of Martha Coakley removes the Democrats’s filibuster-proof majority of 60 votes. Evans calls this a “sideshow.” The real issue is the changing dynamics of Congress when a previously unknown state senator can unseat a Democrat who seemed a sure thing just weeks ago.
Evans notes that 39 House Democrats who voted yes hail from states Obama carried by 10% or less, Evans notes, and of the 18 Democratic Senate seats up in 2010, only 8 are considered solidly Democratic, as Coakley was just weeks ago. Six more seats are toss-ups, and two seem to be leaning Republican. He says he knew health reform was as good as dead in November, and he doesn’t see it coming back. “The only difference now,” he writes, “is that now we know who the killer is: voters.”
GlaxoSmithkline’s Malaria Plan: Limit Profits, Open Labs
Posted by: drugsinus on: January 21, 2010
Drug companies get bashed for not doing enough for killer diseases like malaria that hit the developing world even as they spent hugely on lifestyle drugs for wealthy folks.
GlaxoSmithKline ( GSK – news – people ) Chief Executive Andrew Witty says he has a plan to fix the problem. Witty says he will take about a 5% profit above production costs on GlaxoSmithkline’s experimental malaria vaccine, now in final stage trials in Africa. He doesn’t have a final price yet–it depends on how many doses are produced–but he promised “most people will see this as a good low price.” If the trials succeed, it would be the first vaccine ever for the devastating mosquito-borne disease.
His concept is to make the drug available to poor kids, while still preserving some small profit margin so biotech companies will have an incentive to produce medicines for the developing world in the future. Witty hopes that wealthy nations will step up and form purchasing consortiums to help buy the vaccine for poorer nations.
“We are trying to set the expectation that there will be some return” for creating medicines for poor countries, he said in an interview with Forbes. “If we come out and say it is 0% profit” for the malaria vaccine, there would be no incentive for companies to invest in neglected disease research in the future.
Meanwhile, to jump-start research into drugs for malaria and other neglected diseases, Witty said Glaxo will up its labs to outside nonprofit collaborators. In one project, the company will work closely with Emory University chemists and Alnylam Pharmaceuticals ( ALNY – news – people ) to devise drugs for parasitic worm diseases and other nasty tropical bugs. In another, GSK will open up its lab in Tres Cantos, Spain to as many as 60 academic scientists who want to work on malaria or other developing-world ills. GSK will also make available detailed data on thousands of compounds that have showed some promise against malaria in preliminary tests. The university scientists will be able to develop any drugs they find that look promising.
Witty announced the plans today in a speech to the Council on Foreign Relations in New York and in an interview with Forbes.
“This differentiates GlaxoSmithkline from the rest of the companies. They really want to be partners,” says Emory University chemist Dennis Liotta, who heads the university’s drug discovery institute. “GSK is providing us direct access to the scientists and all of the [internal] reports in the program. … Talking to scientists and finding out what [compounds] are the good ones, that is huge.”
Separately, Mr. Witty says that he supports the general idea behind the plan from the international drug-purchasing agency Unitaid to pool patents on various AIDS drugs and allow generic drug makers to make low cost versions for poor nations. Unitaid hopes a patent pool will lower the prices of important AIDS drugs in Africa, but it needs cooperation from numerous drug makers to make the plan work. So far the plan has generated controversy among drug makers over exactly how many poorer countries would be included. (See: “The Next AIDS Crisis.”) Merck ( MRK – news – people ), Johnson & Johnson ( JNJ – news – people ), and Gilead Sciences ( GILD – news – people ), have come out in general support of the idea, but the position of many other drug companies is not clear.
Witty said that GlaxoSmithkline is in active discussions with Unitaid but calls some of the agency’s previous proposals “light on details.” “We are not going to make a commitment until we know the details,” he says.
Why ObamaCare Will Raise Your Bill
Posted by: drugsinus on: January 18, 2010
“When it becomes law, families will save on their premiums,” President Obama declared in his weekly radio address before Christmas, pitching his health care reform.
If only that were so. Nobody who tracks health insurance sees any sign of softening premium prices for people who already have insurance, ObamaCare or not. Premiums for 2010 were up 10% and are predicted to keep growing at the same rate in coming years.
Health insurance is beginning to resemble air travel–where deep-pocketed business passengers subsidize penny-pinching vacationers. Insurance companies, under the measures in Congress, would be forced to take all comers, young and old, healthy and sick. Over 10 years they would confront $871 billion in spending on uninsured and newly subsidized customers, costs that would be passed along to the young and healthy. The federal government isn’t going to pick up all of that tab, so those now insured through a private plan at work or one bought individually will have to chip in.
If you’re thinking the legislation will tamp down overall health care spending, reconsider. Policy analysts ranging from the neutral Congressional Budget Office to the HMO lobby see no abatement in the growth rate of health care spending. That sector of the economy is growing at a 7.4% annual rate, says actuarial firm Milliman. Medicare’s chief actuary, Richard Foster, thinks the Senate bill would expand health spending by $234 billion above current projections.
The premium hikes will result from cost shifting, better known as passing the buck. The House and Senate insurance bills aim to cover their costs in part by cutting annual Medicare reimbursements to hospitals, doctors and drug companies by $45 billion. Those providers will likely try to offset the cuts by negotiating higher rates with private HMOs–which then get passed along through higher premiums. That’s exactly what occurred after past Medicare and Medicaid cuts, according to the CBO analysis. Families USA, a nonprofit group advocating expanded federal involvement in health care, says insured families are already absorbing $1,000 a year in costs shifted away from uninsured patients.
Also, the legislation requires HMOs to pay $7 billion annually in new fees. That will get passed on to individuals and employers who buy the policies. So-called Cadillac health plans will be taxed at 40%, for anything spent on premiums above $23,000 for a family or $8,500 for an individual, according to the latest Senate bill. The $149 billion this is expected to raise over 10 years will also be passed on directly to employers (and their workers) in the form of higher premiums.
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Complete Coverage: Health
When To Say No To Your Doctor
Find out how much of the $2.5 trillion we spend on health care goes down the drain for tests and treatments that don’t help–and may even cause harm.
Chemical test offers quick prostate cancer check
Posted by: drugsinus on: January 17, 2010
By Michael Kahn
LONDON () – Instead of using a blood test to determine whether a man has prostate cancer, doctors might one day more accurately diagnose the condition using a new technique that measures a different compound, researchers said.
A small study showed how the test within three minutes produced a fingerprint of a chemical called citrate that falls markedly in the prostate gland as cancer develops, David Parker of Durham University in Britain said in a telephone interview.
“Citrate provides a significant biomarker for disease that may provide a reliable method for screening and detecting prostate cancer, and for the monitoring of people with the disease,” said Parker, who helped design the test.
“This technique could form the basis of a simple screening procedure for prostate that could be used in outpatient departments and local hospitals.”
Prostate cancer is the second most common cancer in men worldwide, after lung cancer. It kills 254,000 men a year globally.
Doctors have routinely recommended a blood test called the prostate-specific antigen, or PSA test, to men over 50 in the belief that early diagnosis and aggressive treatment for any cancer is better than standing by and doing nothing.
But many prostate tumors are slow-growing and take years to cause harm. Some studies suggest many men are living with the side effects of aggressive treatment with surgery and radiation for a cancer that may never have killed them.
In their study, Parker and colleagues focused on the compound citrate — which provides energy for cells — in prostate fluid because levels of the chemical decrease markedly when a man has prostate cancer, the researchers said.
The amount of citrate found in the prostate varies depending on an enzyme that is very sensitive to zinc. For men with prostate cancer, zinc levels are depressed which in turn leads to a fall in citrate.
“This technique makes it possible to analyze what is happening in the early and treatable stage of prostate cancer,” Leslie Costello of the University of Maryland said. “It shows much promise as a clinical tool.”
The researchers, who published their findings in the journal Organic and Biomolecular Chemistry, said the new test only requires a microlitre of fluid — a millionth of a liter — as a sample for their test. Researchers typically extract prostate fluid using a needle.
While promising, the technique is at least a few years away from use in hospitals and clinics because the researchers still need to conduct larger trials, Parker added.
Taking the sample is also more invasive than the common PSA test, though the researchers said in the future it may be possible to address that issue.
(Reporting by Michael Kahn; editing by Dominic Evans)
Women who smoke more prone to lung damage: study
Posted by: drugsinus on: January 17, 2010
CHICAGO () – Women may be especially susceptible to the toxic effects of cigarette smoking, U.S. researchers said on Monday.
They said women who smoke develop lung damage earlier in life than men, and it takes less cigarette exposure to cause damage in women compared with men.
“Overall our analysis indicated that women may be more vulnerable to the effects of smoking,” said Dr. Inga-Cecilie Soerheim of Brigham and Women’s Hospital in Boston and the University of Bergen in Norway.
Soerheim, who presented her findings at the American Thoracic Society meeting in San Diego, California, said researchers had suspected this but until now had lacked proof.
Her team analyzed 954 people in Norway with chronic obstructive pulmonary disease, which includes lung problems from chronic bronchitis to emphysema.
COPD affects an estimated 210 million people worldwide. The most common symptoms include shortness of breath, coughing and a limited ability to exercise.
In the study, about 60 percent were men and 40 percent were women. All were current or former smokers.
Overall, both groups had similar lung impairments. But when they looked at younger people — those under age 60 — or those who had been lighter smokers, they found women had more severe disease and worse lung function than men.
“This means that female smokers in our study experienced reduced lung function at a lower level of smoking exposure and at an earlier age than men,” Soerheim said in a statement.
Soerheim suspects the differences may be related to anatomy. Women have smaller airways than men, making each cigarette potentially more dangerous, she said. Hormones may also play a role, she said.
“Many people believe that their own smoking is too limited to be harmful — that a few cigarettes a day represent a minimal risk,” she said in a statement. “However, in the low exposure group in this study, half of the women actually had severe COPD.”
An estimated 12 million people in the United States have COPD, the fourth-leading cause of death.
(Editing by Maggie Fox and Xavier Briand)
Canada sees isotope cooperation during shutdown
Posted by: drugsinus on: January 17, 2010
OTTAWA () – Canada, reacting to the month-long shutdown of a nuclear reactor in Ontario that produces a third of the world’s medical isotopes, said on Tuesday that major isotope producers were addressing the problem of a possible supply shortage cooperatively.
“A secure supply of medical isotopes is not only an issue for Canada; it is an international issue that is being addressed cooperatively by all isotope-producing countries,” federal Natural Resources Minister Lisa Raitt said.
She said the government was engaging international isotope producers as well as companies such as MDS Nordion, the privately held firm Lantheus, and Covidien Ltd, which she said play key roles in securing medical isotope supply for North America.
(Reporting by Randall Palmer; editing by Peter Galloway)
Isotope output at Canada reactor halted after leak
Posted by: drugsinus on: January 17, 2010
By Scott Anderson
TORONTO () – Canadian energy authorities have closed a nuclear reactor that produces a third of the world’s medical isotopes after a small leak and warned that there could be a shortage of isotopes by as early as Saturday.
Atomic Energy of Canada Ltd said it shut down the 50-year-old reactor at Chalk River, Ontario, late last week after it discovered a small leak of heavy water, used as part of the nuclear reaction process.
It expects the reactor to remain out of operation for more than a month.
Meantime, major isotope producing countries and companies are working co-operatively to address the issue of a possible supply shortage, the Canadian government said.
“A secure supply of medical isotopes is not only an issue for Canada, it is an international issue that is being addressed co-operatively by all isotope-producing countries,” Natural Resources Minister Lisa Raitt said.
Raitt said Ottawa was engaging international isotope producers as well as companies such as MDS Nordion, Covidien Ltd, and privately held Lantheus, which she said play key roles in securing medical isotope supply for North America.
The isotopes are used in medical research and in some cancer treatments. When injected into the body, they give off radiation that can be imaged with a camera to diagnose cancer, heart disease and other medical conditions.
Shares of MDS Inc, whose MDS Nordion division has an exclusive agreement to distribute Chalk River’s medical isotopes, were unchanged at C$6.19 after dropping to C$5.94 earlier in the session.
MDS said it expects the financial impact of the shutdown to reduce its adjusted earnings before interest, taxes, depreciation and amortization by about $4 million a month.
The shutdown marks the second time in less than two years the Chalk River reactor has been taken offline. A 2007 production halt resulted in a $9 million drop in profit at MDS.
“In our view, this event will significantly impact MDS’s third-quarter, as Nordion currently provides the majority of MDS profits,” Maher Yaghi, an analyst at Desjardins Securities in Montreal, wrote in a note to investors.
“It will be difficult to calculate the bottom line impact until the precise date of the site’s re-initiation is known,” Yaghi added.
AECL spokesman Dale Coffin said it would take most of the week to assess the situation before providing a definitive timetable for the reactor’s restart.
($1=$1.16 Canadian)
(Reporting by Scott Anderson and Randall Palmer; ;editing by Rob Wilson)
