FDA: Adult Antipsychotic Drugs Effective in Children

WASHINGTON -- Food and Drug Administration staff said Friday three drugs currently approved to treat bipolar disorder and schizophrenia in adults were effective at treating the disorders in children and adolescents, but carry significant risks. The agency is considering applications for AstraZeneca PLC's Seroquel and Eli Lilly and Co.'s Zyprexa to treat bipolar disorder and schizophrenia in children and adolescents, and Pfizer Inc.'s Geodon to treat bipolar disorder in children 10 to 17. An FDA panel of outside medical experts is scheduled to meet to discuss the drugs next Tuesday and Wednesday. The panel is being asked to vote on whether each product is safe and effective for children ages 10 to 17. The FDA as well as the companies said studies showed the products were effective at treating the symptoms of bipolar and schizophrenia, but the drugs all had side effects that included sedation and weight gain. Reviews of the products were posted on FDA's Web site Friday. "These risks are of particular concern in pediatric patients because of the life-long nature of these disorders' said Thomas Laughren, director of the FDA's psychiatric product division, in a memo. The concern with weight gain seen with most antipsychotic drugs whether it causes additional problems like diabetes and cardiovascular disease. The FDA said all three products are already being used in children even though they aren't approved. Approved products include Risperdal, by a unit of Johnson & Johnson, and Abilify by Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., Ltd, the agency said. The FDA asked each company to look at which side effects were more commonly seen in children compared to adults who were studied in clinical trials. Lilly said clinical studies of Zyprexa showed the product was associated with greater weight gain and changes in blood lipid parameters than seen in adults using the product. The company is seeking FDA approval of Zyprexa as a second-treatment for children and adolescents, meaning that other products should be tried first. Zyprexa is Lilly's top-selling drug with $4.7 billion annual sales in 2008. AstraZeneca said side effects that occurred more frequently in children compared to adults on Seroquel included increases in blood pressure and increased appetite. The company also said incidences of certain movement side effects such as tremors were higher among patient taking Seroquel compared to patients in placebo groups, or patients not taking the drug. Seroquel is AstraZeneca's second-best selling drug with $4.45 billion in sales in 2008. Pfizer said children taking Geodon were more likely than adults to report feeling sleepy, or sedation. The company said the drug didn't have a big impact on weight gain with 7% of people taking Geodon experiencing a 7% or greater gain in weight compared to 4% in the placebo group. The company also said the drug didn't increase metabolic markers such as cholesterol. Schizophrenia afflicts about 1% of Americans. According to the National Institute of Mental Health, people with schizophrenia may hear voices other people don't hear or they may believe that others are reading their minds, controlling their thoughts or plotting to harm them. The disorder is also a cause of suicide and is typically diagnosed in a person's late teens or 20s. Bipolar disorder also known as manic-depressive illness, is believed to affect about 1% to 3% of the population, and is characterized by unusual shifts in mood, energy and activity levels. There's evidence that bipolar disorder in children is more severe than typically seen in adults.

2009-06-08 @ 14:00:55 -->[Wall Street Journal]

Major study clears Glaxo's Avandia of heart risk

LONDON, June 5 (Reuters) - GlaxoSmithKline's (GSK.L) controversial diabetes drug Avandia doesn't increase overall heart risks, according to final results of a large clinical study sponsored by the world's second largest drugmaker. The so-called Record trial did, however, confirm that the medicine doubles the risk of heart failure -- a chronic condition where the heart struggles to pump enough blood around the body -- and also increases the danger of bone fractures. Sales of Avandia, once Glaxo's second biggest drug, plunged in 2007 after a pooled analysis of past clinical trials by Cleveland Clinic cardiologist Steven Nissen concluded patients on Avandia had a 43 percent higher risk of heart attacks. Glaxo always contested those findings, arguing Avandia's side-effect profile was no worse than that of other diabetes pills, citing interim results from the Record study to support its case. But because the interim data covered only a limited number of adverse events, they were viewed with some scepticism. Now, with full results in from the study that involved 4,447 patients over 5-1/2 years, Murray Stewart, vice president of clinical development, says Glaxo can deliver a conclusive rebuff to its critics. "The final Record results show there is no difference in cardiovascular death or hospitalisation between Avandia and comparators," he told Reuters in a telephone interview. "At the interim stage we couldn't conclusively say that." The results of the study, which compared Avandia against the older drugs metformin and sulfonylurea, were presented at the American Diabetes Association annual meeting in New Orleans and published online by the Lancet medical journal. Philip Home of Newcastle University, who led the trial, said it was good to have "robust evidence" that Avandia was no riskier than other diabetes drugs, particularly as the drug also proved superior in controlling blood sugar levels. The higher risk of heart failure and fractures was a known effect common to the drug class, he said. Home and colleagues said they could not rule some impact on heart attack incidence but any effect was marginal. "Although our evidence is insufficient to rule out a small increased risk of myocardial infarction (heart attack) caused by rosiglitazone (Avandia) when compared with other glucose-lowering agents, rosiglitazone does not increase overall cardiovascular morbidity or mortality," they wrote. Glaxo's Stewart said the full results of the study would now be assessed by the U.S. Food and Drug Administration, which tightened its warning on Avandia in November 2007. "The FDA have seen the Record data and they've encouraged us to submit the data for consideration in the label, and we will do that," he said. Whether the latest data will be enough to revive Avandia's commercial prospects remains to be seen. Glaxo has only limited time to try to ramp up sales again, since patents protecting the medicine expire in 2012 in the United States and 2013 in Europe. Worldwide sales of Avandia totalled 805 million pounds ($1.29 billion) last year, representing around 3 percent of group sales. In an accompanying Lancet commentary, Ravi Retnakaran and Bernard Zinman of Mount Sinai Hospital in Toronto and the University of Toronto suggested using half-maximum doses of Avandia, since half doses give better-than-half results, while limiting any side effects. (Editing by Dan Lalor) ($1 = 0.6232 pound)

2009-06-08 @ 10:35:38 -->[Reuters]

Pandemic warnings as swine flu spreads to Africa

GENEVA (AFP) – A swine flu pandemic is looming closer with the virus showing early signs of spreading outside the Americas, a WHO official said Tuesday, as Africa reported its first case and Australia's tally soared to nearly 500. "Globally we believe that we are at phase five but are getting closer to phase six," said Keiji Fukuda, World Health Organisation assistant director-general, referring to the agency's six-level pandemic alert system. Phase five signals that a pandemic is imminent while the world would be in a full-fledged pandemic -- marking global spread -- at phase six. "It is clear that the virus continues to spread internationally. We know there are a number of countries that appear to be in transition moving from travel-related cases to established, more established, community-type spread," he added. A criteria for the WHO to move the alert to phase six would be established community spread in a country outside the first region in which the disease was initially reported, in this case, outside the Americas. "However, we still are waiting for really widespread community activity in these countries. So I think it's fair to say that they are in transition and are not quite there yet, that's why we are not in phase six yet," Fukuda said. But he stressed that countries like Britain, Spain, Japan, Chile and Australia were showing larger numbers of A(H1N1) influenza infections, "with some early spread into communities." Other than geographical spread, member states have asked WHO to integrate an assessment of the disease's severity into its criteria for moving up the alert scale and declaring a pandemic. Some 18,965 cases of infections including 117 deaths have been reported to the WHO by 64 countries around the world since the virus emerged in the United States and Mexico in April. The renewed warning came as Canada reported its third swine flu death; two people were hospitalised in Scotland in intensive care, and Egypt and the tiny European duchy of Luxembourg confirmed their first cases of the A(H1N1) virus. The Egyptian case, the first in Africa, involved a 12-year-old girl with joint US and Egyptian nationality who was quarantined by health workers at Cairo airport on Monday after she showed symptoms of the disease. Spain, the first European country to confirm a case of swine flu, on Tuesday reported 13 new confirmed cases at three schools in the Madrid region, one of them a kindergarten, bringing to 15 the total number of children affected. The WHO said on Monday there are 178 confirmed cases of the disease in Spain. France on Tuesday reported its first locally transmitted case and said the number of confirmed infections had risen to 42. The health minister of Australia's Victoria state Daniel Andrews said Tuesday 89 new cases had been identified overnight, taking its total to 395. The national count in Australia now stands at 496, the fourth largest worldwide and the biggest in the Asia-Pacific region. Australia had only one case of swine flu just a fortnight ago but the numbers have grown exponentially since the controversial move to let infected passengers leave a luxury cruise-liner last week. On Tuesday, Carnival Australia warned that another of its vessels had been turned away from the French Pacific territory of New Caledonia because of possible flu cases among its passengers

2009-06-03 @ 10:32:43 -->[AFP]

Anti-clot drug combinations boost bleeding risks

CHICAGO, June 2 (Reuters) - Heart patients are often given two or three different drugs to prevent life-threatening blood clots but these combinations can double, triple or even quadruple the risk of stomach or intestinal bleeding, U.S. researchers said on Tuesday. Clot-preventing drugs such as aspirin, warfarin or Coumadin and clopidogrel or Plavix sold by Bristol-Myers Squibb (BMY.N) and Sanofi-Aventis (SASY.PA) are increasingly being given to heart patients in combinations. "They are often prescribed to prevent that second event -- that heart attack or stroke," Dr. Neena Abraham of Baylor College of Medicine in Houston, Texas, told reporters at the Digestive Disease Week meeting in Chicago. "However, each of these drugs independently is associated with a high risk of clinically significant upper gastrointestinal events, which are defined as ulcers of the stomach or intestines, bleeding or perforations," she said. "These drugs are commonly prescribed in combination; however, the magnitude of the risk of using these drugs on the gastrointestinal tract remains relatively unknown." To study this, Abraham and colleagues used national pharmacy data and medical records from the Veterans Affairs Department to identify people aged 60 to 99 who had been given four combinations of clot-preventing drugs. Some got aspirin and an antiplatelet drug like Plavix that keeps blood platelets from forming clots. Others got an antiplatelet drug and an anticoagulant such as warfarin, which keeps the liver from making certain clotting factors. Some got aspirin and warfarin. And some got all three. Of the more than 78,000 patients studied, 30.4 percent were prescribed some combination of anticlotting drugs, and 1,061 of these had bleeding events that needed immediate medical attention within the first year. RISING RISK "When we compared the risk of bleeding from these different combinations, what we see is a stepwise increase in risk," Abraham said. The dual combination of an anticoagulant and antiplatelet drug, which proved to be least harmful, raised the risk of a serious bleeding problem within one year by 70 percent. A combination of an aspirin and antiplatelet drug doubled the risk, while an aspirin-anticoagulant combination tripled the one-year bleeding risk. And patients who got all three drugs had a four-fold increase in the risk of gastrointestinal bleeding within one year, Abraham said. "These are significant gastrointestinal bleeding risks." Abraham said triple therapy was most commonly given to younger patients in the study -- those aged 60 and 69 years of age -- and likely reflected recent changes in cardiac care. She said the findings suggest the need for a careful balancing of the risks and benefits of these drugs. Heart patients on triple therapy may want to ask their doctor about dropping down to a dual or single therapy. "We know they are healthy for the heart at preventing strokes and heart attacks, but what physicians now need to consider is short-term potential risks of GI bleeding versus the potential long-term benefits of being on these protective drugs," she said.

2009-06-03 @ 10:32:43 -->[Reuters]

Study: Drug Doesn’t Reduce Repetitive Behaviors in Autism

By Shirley S. Wang The government is putting more money into researching autism because there aren’t a lot of good treatment options, and a study published today seems to underscore the point. The report on a large, NIH-funded trial found the popular antidepressant citalopram doesn’t appear to help kids with autism-spectrum disorders to reduce repetitive behaviors, one of the core characteristics of the condition. Antidepressants like citalopram, part of a class called SSRIs, were thought to help treat autism because they help kids with obsessive-compulsive disorder who also exhibit repetitive behaviors. Citalopram is sold as a generic by several companies and as Celexa by Forest Labs. In this randomized, controlled study, 149 children with autism and related disorders were treated with either citalopram or a placebo for 12 weeks. At the end, there wasn’t any difference between the groups in general functioning or in their repetitive behaviors. About 30% from each group were considered “much improved” at the end of the treatment period. “In fact these medications may not be what we once that they would be, at least for children,” Yale psychiatry professor Fred Volkmar, who wrote a commentary accompanying the study, told the Health Blog. “Clinicians need to think carefully, as they always do, about psychopharmacology in children.” Though this study is about one drug, there is “some worry” about the effectiveness of the whole class of SSRIs in treating repetitive behaviors in autism, Volkmar added. Thomas Insel, director of the National Institutes of Mental Health who wasn’t involved in the study, characterized the findings as “disappointing”. “We’re still at a point where we don’t have medications for the core symptoms: deficits for social behaviors, problems with language and repetitive behaviors,” Insel told the Health Blog. “We don’t have medical interventions that have been demonstrated to be effective in double-blind controlled trials.”

2009-06-02 @ 22:11:27 -->[WSJ Blogs]

Drugmaker to pay nearly $100 million settlement

Drugmaker Sanofi-Aventis has agreed to pay nearly $100 million to settle allegations it cheated Medicaid on the cost of nasal sprays. The Justice Department said Aventis Pharmaceutical Inc., a wholly owned subsidiary of Sanofi-Aventis U.S. LLC, has agreed to pay the government $95.5 million to settle the charges. The government charged that between 1995 and 2000, Aventis and its corporate predecessors did not offer Medicaid the best prices for the sprays Azmacort, Nasacort and Nasacort AQ. Medicaid is a state and federally funded health care program for the poor. In reaching the settlement, Sanofi-Aventis U.S. did not admit any wrongdoing. The company, based in Bridgewater, N.J., issued a statement saying it believed the old pricing system was legal. The global parent firm is based in Paris and has 100,000 employees operating in more than 100 countries. Michael Loucks, the U.S. Attorney for Massachusetts, said the government will vigorously investigate those who scam the Medicaid system. Under the law, the company was required to tell Medicaid the lowest price that it charged companies for those products, and offer state Medicaid programs rebates based on those prices. Prosecutors contend that in order to dodge that obligation, Aventis entered into a private deal with the HMO Kaiser Permanente that repackaged Aventis drugs under a new label, allowing them to overcharge Medicaid programs for the same product. From the $95.5 million settlement, the U.S. government will get slightly more than half. More than $40 million will go to the states providing Medicaid, and over $6 million to public health service firms that paid inflated prices. The settlement comes days after another unit of the company won a $190 million contract from the U.S. government to make a swine flu vaccine. The Justice Department earlier this month accused Wyeth, one of the nation's biggest drugmakers, of cheating Medicaid programs out of hundreds of millions of dollars by overcharging for a stomach acid drug. Wyeth defended its pricing plan, saying its pricing calculations were correct.

2009-05-31 @ 11:51:57 -->[AP]

Catalyst Pharma cocaine addiction drug fails

May 29 (Reuters) - Catalyst Pharmaceutical Partners Inc (CPRX.O) said its lead drug candidate to treat cocaine addiction failed to meet its main goal in a mid-stage trial. The company, which reaffirmed that it had enough cash to continue operations till the end of 2010, said the drug CPP-109 could not show that a significantly larger proportion of subjects treated by it were cocaine-free during the last two weeks of the treatment period, compared with a dummy drug. The company said it would determine the next steps regarding the development of the drug based on the complete analyses of the clinical trial data. Catalyst expects to complete the analyses during the third quarter after fully unblinding the trial data. In March, Catalyst said it had halted enrollment of new subjects in an ongoing mid-stage trial testing CPP-109 for the treatment of methamphetamine addiction in order to extend its cash resources into 2010. The company had decided to instead convert that trial to a smaller proof-of-concept study. "We have sufficient cash to complete the analysis of the results from our cocaine trial, to complete our methamphetamine proof-of-concept study and to continue our operations through the end of 2010 without additional funding," Chief Executive Patrick McEnany said in a statement. Shares of the company closed at $2.10 Thursday on Nasdaq. (Reporting by Esha Dey in Bangalore; Editing by Himani Sarkar)

2009-05-31 @ 11:51:57 -->[Reuters]

Abbott Heart Drug Faces Key Test In Large US Study

A top-selling but controversial Abbott Laboratories (ABT) cholesterol drug faces a key test when a U.S. government study ending next month shows whether it actually prevents heart attacks and related disease. Abbott's TriCor is known to improve levels of cholesterol and related substances, but there is skimpy proof this translates into better cardiovascular outcomes - even though the drug is more than 30 years old. The $300 million government study, titled "Accord," could address the evidence gap. "It's widely used and the question is, does it really have an impact on things we care about, which are death, heart attack, stroke and related complications?" said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, who isn't directly involved in the government study. The study's outcome could help or hurt future sales of TriCor, which totaled $ 1.3 billion for 2008, as well as a new, similar drug from Abbott called Trilipix. The data also have implications for AstraZeneca PLC (AZN) because it and Abbott are co-developing a single-pill combination of Trilipix and Astra's cholesterol drug Crestor, which the companies expect to submit for U.S. regulatory approval later this year. Some expect negative news for Abbott. Wachovia analyst Larry Biegelsen said there's a high chance TriCor will fail to meet the study's primary goal of showing a benefit, which could hurt Abbott's profits (though he thinks TriCor could show benefit among study subgroups or on secondary goals). Concerns about the Accord study factored into his downgrade of Abbott shares in early April. Abbott shares are off about 16% year-to-date on worries about sales growth of top products, trading recently around $44.60. The National Institutes of Health started the 10,250-patient study in 1999 to test various approaches for lowering the risk of heart attacks, strokes and cardiovascular death in people with type 2 diabetes. They include drugs to control blood sugar, reduce blood pressure and improve cholesterol levels. The mix of generic and brand-name drugs have been supplied by major manufacturers including GlaxoSmithKline PLC (GSK), Novartis AG (NVS) and Merck & Co. (MRK). Abbott licensed TriCor, known generically as fenofibrate, from French drug maker Fournier in the late 1990s. Doctors prescribe TriCor to help lower levels of bad cholesterol and triglycerides, which are chemicals in the blood derived from fats, and to raise good cholesterol. The Accord trial tests whether adding TriCor to cholesterol drug simvastatin - sold as Zocor by Merck and available as a generic - is any better than simvastatin alone at improving cardiovascular outcomes. The TriCor arm of the Accord study was left intact last year when the NIH stopped another study regimen, intensive reduction of blood sugar, due to safety concerns. The low-intensity blood-sugar reduction and the blood-pressure- lowering aspects of the study also continue. Several of the drugs used in these groups are available as generics but also include branded drugs such as Glaxo's Avandia. Some doctors are skeptical about the benefits of TriCor. Past studies have failed to show definitively that it reduces heart attacks and related disease, and some studies have raised the possibility it could cause kidney problems. Abbott has defended the drug's efficacy and safety, saying there's no evidence it boosts the risk of kidney problems. A study released last week concluded the drug reduces the risk of diabetes-related limb amputations. Abbott also cautions that the design of the Accord trial could mute TriCor's benefits. James Stolzenbach, an Abbott divisional vice president, said the average participant started the Accord trial with lower triglyceride levels than the typical patient using TriCor today. Thus, it might be more difficult to demonstrate that adding TriCor to simvastatin makes a big difference, he said. Stolzenbach said "it's really unlikely" that the Accord study's outcome will have an effect on whether the average TriCor user would continue on the drug, or on doctor's prescribing decisions. Accord study participants are scheduled to finish doctor's office visits by the end of June, then researchers will analyze the data. An NIH spokeswoman said researchers are still working on a timeline for presenting the results. Some people expect them to be presented at the annual scientific sessions of the American Heart Association in November.

2009-05-31 @ 11:41:37 -->[nasdaq]

EU drugs watchdog backs generic versions of Plavix

LONDON, May 29 (Reuters) - The European Medicines Agency has given a green light to six generic versions of Sanofi-Aventis (SASY.PA) and Bristol-Myers Squibb's (BMY.N) blockbuster blood thinner Plavix, it said on Friday. The new generics are Clopidogrel 1A Pharma, Clopidogrel ratiopharm, Clopidogrel Acino and Clopidogrel Hexal, all from Acino (ACIN.S); Clopidogrel Teva, from Teva (TEVA.TA); and Grepid, from Pharmathen. Acino, a generic drugmaker which was formerly known as Schweizerhall, has been selling generic Plavix in Germany since last year and the company said in January its generic version had already captured about a quarter of the German market. The move by the European drugs watchdog clears the way for wider generic Plavix sales following the initial German approval and launch. Recommendations for marketing approval by the agency's Committee for Medicinal Products for Human Use are normally endorsed by the European Commission within a couple of months. Plavix is one is one of the world's most successful medicines, with sales last year of around $8 billion. It works by stopping platelets -- tiny blood cells vital for the normal clotting process -- from clumping together and forming life-threatening clots. Sanofi and Bristol recently defeated generic competition to Plavix in the United States, but the two partners have been facing a broad generic threat in Europe following Acino's launch in Germany. (Reporting by Ben Hirschler; Editing by David Holmes)

2009-05-31 @ 11:41:37 -->[Reuters]

Fenofibrate Cuts Risk of Diabetes-Related Amputation

LITTLE FALLS, N.J., May 21 -- Fenofibrate reduces the risk of amputation for patients with type 2 diabetes, a large randomized trial showed. Action Points   Explain to interested patients that this study found that the risk of minor amputations without large-vessel disease in patients with type 2 diabetes was reduced in those taking fenofibrate. Point out that amputation was a tertiary endpoint of this large, randomized controlled trial. The benefit was driven by a 47% decrease in the risk of minor amputations in the absence of known large-vessel disease (P<0.027), according to Kushwin Rajamani, M.B.B.Ch., of the University of Sydney, and colleagues. There was an absolute reduction of 0.5% in the risk of any amputation, the researchers reported in the May 23 issue of The Lancet. Although the mechanism of action remains unclear, they said it is unlikely that it involves lipids because none of the lipid variables were associated with the risk of amputation after controlling for several factors. "These findings could lead to a change in standard treatment for the prevention of diabetes-related lower-limb amputations," the researchers concluded. Agreeing in an accompanying editorial were Sergio Fazio, M.D., Ph.D., and MacRae Linton, M.D., of Vanderbilt University in Nashville, Tenn. Considering the failure of statins to prevent diabetes-related amputations, they wrote, "we should marvel at the unexpectedly large effects of treatment with a fibrate." About 10% of diabetics will require at least one amputation, according to Dr. Rajamani and colleagues. These amputations account for an estimated $1.6 billion in healthcare costs in the U.S. each year. To assess the effectiveness of fenofibrate in modifying amputation risk, the researchers turned to the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The trial randomized 9,795 diabetics ages 50 to 75 (mean 62.2) to 200 mg of fenofibrate a day or placebo and followed them for five years. All patients received optimal medical treatment. Fenofibrate failed to reduce the risk of cardiovascular death or myocardial infarction -- the primary endpoint -- compared with placebo. (See AHA: Fibrate Fails to Reduce Heart Disease Deaths in Diabetics) It did, however, reduce the need for laser therapy for retinopathy. (See Fenofibrate May Protect Against Diabetic Retinopathy) Amputation risk was a prespecified tertiary endpoint of the trial. Overall, 115 patients had at least one lower-limb amputation due to diabetes. Risk of amputation was 36% lower in patients taking fenofibrate (HR 0.64, 95% CI 0.44 to 0.94), attributable to a 47% reduction in the risk of minor amputations -- those below the ankle -- absent known large-vessel disease (HR 0.53, 95% CI 0.30 to 0.94). The risk of major amputations above the ankle and minor amputations with large-vessel disease did not differ between the groups. The benefit of fenofibrate was not modified by use of ACE inhibitors or angiotensin-receptor blockers or by level of glycemic control. The strongest predictors of amputation were a history of nontraumatic amputation or skin ulcer, neuropathy, and peripheral vascular disease (P<0.0001 for all). In addition, each additional 10 centimeters of height was associated with a 60% increase in risk (P<0.0001). Each additional three years in age increased the risk by 30% (P<0.0001). "The number of patients needed to treat with fenofibrate over five years to prevent at least one amputation in one patient is 197, but is 25 for someone with previous foot ulcer and albuminuria," the researchers said. Drs. Fazio and Linton, the editorialists, wondered whether the beneficial effects of fenofibrate might involve improvements in wound healing. "This effect -- more so than anti-inflammatory, antioxidant, or endothelium-mediated effects -- would set fibrates apart from the many agents (statins, antihypertensives, aspirin, and vitamin E) that have so far been unable to reduce amputations in people with diabetes." The study authors acknowledged that the study was limited by the lack of routine testing of vascular status at baseline. The study was supported by a grant from Laboratoires Fournier SA and by the National Health and Medical Research Council (NHMRC) of Australia and was coordinated independently by the NHMRC Clinical Trials Center at the University of Sydney and overseen by the study Management Committee. Dr. Rajamani's co-authors reported potential conflicts of interest with Eli Lilly, Novo Nordisk, GlaxoSmithKline, sanofi-aventis, BayHill, Medtronic, AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, Novartis, Fournier, Takeda, Solvay, Abbott, and Roche Diagnostics. One of the study authors has served as an expert witness for Medicines Australia and has been named in a patent application related to fenofibrate and diabetic retinopathy. Dr. Fazio has received honoraria for lectures from Merck, Schering-Plough, GlaxoSmithKline, and Abbott. Dr. Linton has received honoraria for lectures from Merck, Schering-Plough, AstraZeneca, and Abbott. Both editorialists have received support for clinical trials from Merck Schering-Plough, ISIS, Genzyme, and AstraZeneca.

2009-05-23 @ 10:37:25 -->[medpagetoday]

U.S.' new drug czar targets prescription abuse as priority

"We get overly concerned about drugs coming in, but the pharmaceuticals are here already," he said in an interview Wednesday with USA TODAY. He says he'll push for more states to adopt prescription-monitoring programs, databases in which doctors and pharmacists log prescriptions for addictive drugs so law enforcement can track them. Kerlikowske, who became director of the White House Office of National Drug Control Policy on May 7, described drug abuse as a "public health problem." Yet the former Seattle police chief added: "That doesn't mean law enforcement doesn't have a role to play." He said he was stunned to learn recently that more people in the U.S. die from drugs than from gunshot wounds. "We're going to shout that from the rooftops," he said. "We have a national effort to combat swine flu. In the same way, we can bring all forces to bear on the drug problem." Kerlikowske said he supports drug courts that offer treatment instead of prison for addicts and needle-exchange programs to stop the spread of disease. His approach departs from that of the Bush administration, which heavily funded law enforcement task forces and advocated for tough sentences for drug offenders. The Obama administration wants to make sentences for crimes involving crack cocaine the same as sentences for crimes involving powder cocaine. Right now sentences are longer for crack cocaine-related crimes. Attorney General Eric Holder also has limited prosecutions of sick people or caregivers who use or dispense marijuana for medical reasons. He has said his agents will seek criminal charges only when both state and U.S. laws are violated. During the Bush administration, agents raided several centers that dispense marijuana in California, where state law permits its medical use. On his first trip outside Washington since assuming his new role, Kerlikowske told a law enforcement crowd Wednesday that marijuana should remain illegal, but public health officials — not police — should lead efforts to reduce illegal drug use. "Legalization isn't in the president's vocabulary, and it certainly isn't in mine," he told 300 police, federal agents and law enforcement officials. He sought to show strong support for law enforcement, making his first stop a 6:30 a.m. roll call at a Nashville Police Department precinct. After speaking at the conference, Kerlikowske visited a drug court with a residential-treatment center. He also toured a residence for women with addictions who were recently released from prison. "The state of Tennessee has built all the prison cells it needs" but has not invested enough in treating drug abusers, Criminal Court Judge Seth Norman, who runs the Davidson County Drug Court, told Kerlikowske. The new drug czar agreed: "Rotating people in and out and through the system doesn't make a lot of sense."

2009-05-23 @ 10:34:16 -->[usatoday]

Comparison is Key to Lower Costs, Better Outcomes from Medications

Newswise — Patients can expect significant savings and better outcomes from their prescription medications when health care professionals use comparative effectiveness research, according to researchers at the University of Illinois at Chicago. The American Recovery and Reinvestment Act signed by President Obama includes more than $1 billion over the next two years for comparative effectiveness research, a practice that evaluates different options for treating a medical condition among a certain group of patients. "Despite having the highest per capita health care expenditures in the world, the United States does not always perform well on measures of health compared with other countries," said Glen Schumock, associate professor and director of the UIC Center for Pharmacoeconomic Research. "With prescription drugs accounting for more than 10 percent -- $227.5 billion -- of the total amount Americans spent on health care in 2007, we need to know more about how drugs compare to one another in terms of effectiveness, safety, and value for money." The analysis is published in the online version of American Journal of Health-Systems Pharmacy and is co-authored by A. Simon Pickard, UIC associate professor of pharmacy practice. Comparative effectiveness is a relatively new concept, and it contains two important components, Schumock said. It provides information to help clinicians choose among alternative treatments, and it examines outcomes in actual practice. Randomized control trials have long been the most widely accepted method to study the efficacy of innovative medical care interventions, and they are required by the U.S. Food and Drug Administration to market a new drug, Schumock said. However, such trials have drawbacks. A traditional randomized control trial does not show how the drug works, Schumock said, "and it usually compares a new drug with a placebo or an inferior treatment option rather than the drug or drugs that might be legitimate therapeutic alternatives." The patient populations are also narrowly selected, and are usually healthier than the patients who will eventually use the drug, he said. Comparative effectiveness studies matches up comparable medications based on current choices available to health care professionals. The patients are those who actually use the drug once it is marketed. The outcomes, Schumock said, are more relevant to decisionmaking at the clinical or policy level. Comparative effectiveness research may reduce spending on pharmaceuticals and lower overall health care costs, said Pickard. According to the Congressional Budget Office, direct spending by the federal government -- mostly for Medicare and Medicaid -- would be reduced by $100 million from 2008-2012 and $1.3 billion from 2008-2017. Those figures could be much higher, as they were developed before the recent large investment in comparative effectiveness research, Pickard said. "With the shared goal of improving decisionmaking at every level of the health care system, pharmacy and other professions can use comparative effectiveness research as an opportunity to be more efficient and more accountable," Pickard said. For more information about UIC, visit www.uic.edu.

2009-05-23 @ 10:28:27 -->[newswise]

Novartis eyes blockbuster sales for new lung drug

ZURICH, May 21 (Reuters) - A new medicine from Novartis AG significantly improved lung function when compared with two established respiratory drugs in late stage clinical tests, boosting hopes it could be a $1 billion-a-year seller. The drug, known as QAB149, is being reviewed for approval in the European Union and the United States. Trevor Mundel, head of development at Novartis Pharma, said the drug could be on the market next year and has the potential to be a big seller. "I think QAB becomes a very substantial opportunity," Mundel told Reuters. "I think heading towards a blockbuster." Blockbusters are defined in the pharmaceuticals industry as products with annual sales of $1 billion or more. All doses of once-daily QAB149 met their main target in Phase III trials for treating chronic obstructive pulmonary disease (COPD), or "smoker's lung", the Swiss drugmaker said on Thursday. The medicine showed significant improvements over bronchodilators formoterol and tiotropium and significantly improved lung function from the first day of therapy to up to one year of treatment, Novartis said. Formoterol is marketed under various trade names by companies including Novartis, Schering-Plough Corp, and AstraZeneca Plc. Tiotropium is the generic name for Spiriva, marketed by Pfizer Inc and Boehringer Ingelheim. Novartis is planning to use QAB149 both on its own and as the base of combination treatments with other lung medicines. One such combination product is QVA149 -- a mix of QAB149 and Vectura Group Plc's (VEC.L) NVA237 -- which is expected to enter Phase III clinical trials in the fourth quarter. Another is QMF149, which combines QAB149 and Schering-Plough's mometasone, for which Novartis assumed worldwide rights in a deal announced earlier this week. "Novartis has a growing respiratory pipeline, which we believe has not been a key investor focus ... QAB149 is the cornerstone for a large number of potentially valuable future combinations," analysts at Citigroup said in a research note. Piper Jaffray analysts said the latest good clinical data boded well for QVA149 and Vectura's partnership with Novartis. Shares in Vectura rose 2.6 percent in early trade. Novartis was untraded due to a holiday in Switzerland. COPD is a debilitating and progressive respiratory disease that affects around 210 million people worldwide. It is commonly caused by cigarette smoke and is characterised by a persistent obstruction of airflow in the lungs which results in breathlessness.

2009-05-23 @ 10:24:47 -->[ Reuters ]

Acting US FDA chief defends rise in industry fees

WASHINGTON, May 21 (Reuters) - The acting head of the U.S. Food and Drug Administration defended the agency's request for more funding, including an increase in fees from industries the agency regulates. Democrats debating the FDA's budget voiced concern annual increases in industry fees might compromise the agency's work. "I understand the concern that people ... have expressed that user fees create a perception or a conflict of the agency's work," Acting FDA Commissioner Joshua Sharfstein told a U.S. House of Representatives appropriations subcommittee. "I think these concerns reflect a broader lack of trust in the FDA." To alleviate unease, the new FDA leadership under President Barack Obama must "renew the public's confidence by acting with integrity and transparency" and send "the signal inside and outside the agency that we will make decisions based on the best available scientific evidence and not on influence that's inappropriate." For fiscal 2010, Obama has asked the Democratic-controlled Congress for an FDA budget of $3.2 billion, including $828 million in fees from manufacturers of medical and food products. The fees include hundreds of millions of dollars drugmakers pay annually to help speed the review of new medicines. Obama's budget plan also seeks new fees to help clear a backlog of generic drug applications and to reinspect food and medical product plants that fail to meet FDA standards. Democratic Representative Maurice Hinchey said the growing percentage of fees from drugmakers "is something of great concern for a number of people on this committee." Sharfstein, speaking to reporters, said he did not think the industry fees had risen too high. Republicans, meanwhile, said it may be difficult to win authority from Congress to collect the new types of fees. "Every administration rolls out user fees and yet rarely do user fees get beyond this (subcommittee) hearing," said Republican Representative Jack Kingston. Sharfstein also said he wanted the FDA to be more proactive in encouraging development of new treatments. "We want to help get drugs to people who need them. At the same time we want to reduce the safety concerns. Both parts of the equation are important to us," he said at a separate hearing before a Senate Appropriations subcommittee. Stem cell research is one emerging field in which the FDA may be able to provide guidance on development before any products are submitted for approval, Sharfstein told reporters. Sharfstein, the FDA's principal deputy commissioner, is serving as the agency's acting chief until Dr. Margaret Hamburg steps into the top job. Hamburg was confirmed by the Senate on Monday. Sharfstein expected her to be sworn in as FDA commissioner next week.

2009-05-23 @ 10:24:47 -->[ Reuters ]

N.J.-based Roche shedding more than 1,500 jobs in Genentech deal

Swiss drugmaker Roche, which has run its U.S. operations from a campus in Nutley for 80 years, plans to shed more than 1,500 jobs in New Jersey and relocate major operations to California as part of a $46.8 billion deal to take over the biotech powerhouse Genentech. Roche will keep the heart of its business -- some 1,600 researchers and scientists -- in Nutley to work on new medicines to treat cancer and metabolic disorders such as diabetes and obesity. A contingent of scientists who are studying treatments for inflammatory diseases at Roche laboratories in Palo Alto, Calif., also will eventually be moved to Nutley. "Roche is changing the nature of the Nutley campus," spokesman Al Wasilewski said today. "We don't see it as leaving." Most of the 1,500 job cuts will be in commercial operations, largely sales and marketing personnel, he said. The merger of Roche and Genentech, announced today, reflects further erosion of one of New Jersey's leading industries. In January, Pfizer set off an expected wave of industry consolidation when it announced it would acquire Wyeth, another New Jersey pharmaceutical company. And on Monday, the mega-merger of Merck and Schering-Plough was announced. Roche, which already owned more than half of Genentech, agreed to pay $95 a share for the remaining 44 percent of the South San Francisco-based biotechnology company. The agreement ended a long, and at times tense, corporate struggle between the two companies. In July, Genentech's board of directors rejected Roche's initial offer of $89 a share. After lowering its offer once to $86.50, Roche upped the bid on Friday to $93 a share, signaling an apparent compromise in the talks. As part of the deal, Roche's U.S. pharmaceutical business will begin operating under the Genentech name. One analyst, Michael Latwis with Decision Resources, said forfeiting the Roche name was a "small concession." "Genentech is really the major growth engine," Latwis said. "Roche's portfolio is not growing nearly as fast without Genentech's products." What disappears with the name, however, is some of the storied history of a drug company that became a landmark as it added office buildings and laboratories across 125 acres straddling Nutley and Clifton. Wasilewski said the company is redoing a campus master plan to determine what can be done with the buildings being vacated. Other buildings, including the Roche Tower, are already being renovated. "What we're doing is reconfiguring the landscape of the campus," he said. The new wave of consolidation -- as well as worsening economic conditions -- weighed on some Roche employees today as the finality of the Genentech deal set in. Fewer pharmaceutical companies mean fewer opportunities for them to move around the industry. "I think a lot more people are afraid than when they first heard (about the merger)," said Patricia Woelpper, who has worked at Roche for 18 years. "Where are we going to go?" Inside the Park Pub restaurant, a short distance from the Roche campus in Nutley, an engineer who asked to remain unidentified said managers have been bracing employees about the sale for some time. "They have over-communicated the information," he said, sitting with a co-worker at lunch time. "You can't be upset, but there's still that uncertainty. Who stays and who moves on?" Created in 1896 in Basil, Switzerland, Roche moved its U.S. operations to Nutley in 1929. The business began producing vitamins -- a business it later moved to Warren County -- and then returned to making medicines, including widely-used tranquilizers such as Librium and Valium. Roche developed several other leading medicines for Parkinson's disease and psoriasis. The company began its collaboration with Genentech in 1980, reaping huge profits from cancer medicines such as Avastin and Herceptin. But Roche also pushed out its own key products, including Neupogen for cancer and Hivid, the company's first HIV-antiviral drug. Latwis, the analyst with Decision Resources, said Roche's takeover of Genentech locks up its ability to continue to access Genentech's strong portfolio. The need to push out new medicines is one of the forces driving consolidation in the pharmaceutical industry, but now that pressure is compounded by intensifying generic competition, intensifying regulatory scrutiny and a global economic recession.

2009-03-15 @ 10:43:54 -->[Star-Ledger]

Pfizer’s Cancer Drug Sutent Helped Pancreatic Tumors

Pfizer Inc.’s cancer drug Sutent showed “significant benefit” in patients with a form of pancreatic tumor, the company said. The finding prompted Pfizer, the world’s largest drugmaker, to stop human tests early because it would have been unethical to continue giving some patients a placebo instead of the medicine, the New York-based company said today in a statement. Sutent, already approved for use against kidney and stomach cancer, had $847 million in sales last year. The study looked at patients with advanced pancreatic islet cell tumors, also known as pancreatic neuroendocrine tumors. Apple Inc. Chief Executive Officer Steve Jobs said he was diagnosed in 2004 with that form of malignancy. “Sutent provides a benefit for patients with advanced, well-differentiated pancreatic islet cell tumors -- a rare cancer with limited treatment options,” said Mace Rothenberg, senior vice president of medical development and clinical affairs for Pfizer, in a statement. Pfizer needs new treatments to help make up for the $10 billion it will start losing in 2011, when competitors begin selling generic copies of Lipitor, its top-selling cholesterol pill. The neuroendocrine islet cell tumors are a rare, slow- growing cancer that afflict as many as 3,000 people in the U.S. annually. The tumors tend to overproduce insulin and other hormones. Excess hormones can lead to low blood sugar, low blood pressure or other symptoms. Neuroendocrine tumors that originate in the pancreas, as Jobs’s did, often spread to the liver.

2009-03-15 @ 10:12:59 -->[bloomberg]

Roche to take over Genentech for $47 billion

NEW YORK (AP) -- Swiss pharmaceutical giant Roche agreed Thursday to pay $46.8 billlion in cash to buy the 44 percent of California-based biotech pioneer Genentech that it doesn't already own, ending a long corporate struggle between the companies. The deal, which values the whole of Genentech at more than $100 billion, underscores the lengths drugmakers are willing to go to shore up weak pipelines of new drugs. And investors and the industry will be watching to see if Roche can preserve the unique research culture that helped Genentech all but start the biotech industry. The $95-per-share deal brings Roche, whose best-known products include the flu treatment Tamiflu and the tranquilizer Valium, all of the sales of Genentech's highly profitable cancer drugs as well as its promising research pipeline and scientific corporate culture. The deal, which is a tender offer approved by Genentech's board, offers $95 per share for the 44 percent of South San Francisco, Calif.-based Genentech Inc. that Basel-based Roche Holding AG doesn't already own. A majority of shares besides Roche's still must be tendered for the deal to happen, with a deadline of March 25. It is the latest in a burst of megadeals among drugmakers, following Merck & Co. Inc.'s announcement Monday that it would acquire Schering-Plough Corp. and Pfizer Inc.'s pending acquisition of Wyeth. A dearth of new products and push for cost savings are driving the rush to combine. The deal values Genentech as a whole at $100.1 billion when including the portion of the company already owned by Roche. That nearly matches the $109.1 billion combined total for Merck's and Pfizer's acquisitions. Roche expects to save $750 million to $850 million per year by eliminating duplication but has not yet given a figure for potential job cuts. The agreement ends Roche's hostile bid for Genentech. Genentech's board rejected Roche's initial friendly bid of $89 per share in July. Roche then surprised the company and Wall Street with a lowered $86.50-per-share bid on Jan. 30, aimed directly at shareholders. The Swiss drugmaker then increased that bid to $93 per share last Friday. Roche recently said it raised $36 billion in financing and can obtain the rest through debt or with available cash. Hanging over the negotiations have been study data expected to be released in April on the effectiveness of Genentech's Avastin in treating early-stage colon cancer. The drug, Genentech's best-selling product, is already approved for various types of breast, lung and colon cancers. Avastin is one of the best-selling biotechnology drugs in the world. Like other biotech drugs, it is made using living cells. The process though is more complicated and often more costly than traditional chemical drugs, which makes biotech drugs more expensive. Avastin, for example, can cost about $50,000 per year. With the government looking to help control prescription drug prices, consolidation could turn out to be a good thing for the industry, said Morningstar equity analyst Damien Conover. The move allows for sales force and other cuts, which could help maintain margins if drug prices decreased, he said. "The other piece is if you are bigger you tend to have more negotiating power," he added. Roche said the combined company would be the seventh-largest U.S. pharmaceutical company in terms of market share and would generate about $17 billion in annual revenue with a payroll of around 17,500 employees in the U.S. pharmaceuticals business alone. Genentech has about 95 percent participation in its employee stock program. Based on an analysis of recent regulatory filings, employees stand to reap more than $2 billion altogether from those options, with the top excutives included. "Working together, we aim to close the transaction quickly, thus removing uncertainty for employees and allowing us to focus even more intently on innovation and long-term projects," Roche Chairman Franz B. Humer said. Roche said its Pharma commercial operations in the U.S. will move from Nutley, N.J., to Genentech's site in South San Francisco, which will become headquarters of the company's U.S. drug operations and operate under the Genentech name. It said this would take advantage of "the strong brand value of Genentech in the U.S. market." Investors remained concerned over how the culture at Genentech, which is known for cutting-edge research and as a place where scientists can flourish. It is key component to the company's success, several have said. "This is where I see it as being a little negative," Conover said, referring to the buyout. "A lot of scientists will stay because of funding with Roche, but a lot of entrepreneurial people may decide to move on." Roche said potential management changes are still under discussion, which leaves unanswered questions surrounding the future role of Genentech Chief Executive Arthur D. Levinson. "He's a very enthusiastic and excitable guy. To me, it would make a lot of sense to keep him there as a figurehead if you're trying to maintain the culture," Tanner said. Levinson joined the company in 1980 as a senior scientist and worked his way up to CEO in 1995. In that role, he helped shift the company into a blockbuster drug powerhouse and one of the top producers of cancer treatments in the world. The weak economy and consolidation within the sector, though, could stave off an exodus. Leerink Swann analyst Bill Tanner said it will be a matter of how well Roche maintains the environment. "They may have some cover now that pharmaceutical companies are cutting back," he said. Research and early development will operate as an independent center within Roche from Genentech's campus in South San Francisco, it said. Roche shares closed 1.1 percent higher at 147.10 Swiss francs ($126.80) on the Zurich exchange. Genentech shares rose $1.75 to $93.92. Associated Press Writer Alexander G. Higgins contributed to this story from Geneva.

2009-03-15 @ 10:34:00 -->[yahoo]

AstraZeneca's Seroquel Research Director Confessed to Sex-for-Studies Affairs

Former AstraZeneca U.S. medical director for Seroquel Wayne MacFadden confessed his multiple sexual affairs, and his offer of drugs to one of the women he was sleeping with, to lawyers in December 2007. The confessions include descriptions of sex in hotel rooms paid for by AZ, illicit distribution of Vicodin, and a kinky relationship in which one of his colleagues asked to be “punished” for looking at a study that had negative results for Seroquel. MacFadden told that woman: “You will be punished (in the usual fashion!) when I see you … but perhaps more harshly this time!!!” He made the confession to the lawyers — who are suing AstraZeneca for allegedly failing to warn patients that side effects of the drug include significant weight gain and diabetes — as part of a deposition prior to the current litigation going on in Florida. (See BNET’s back story, “Email: AstraZeneca Knew in 1997 That Seroquel Caused Weight Gain.”) Between 2002 and 2006, MacFadden said he had slept with two executives who worked for AZ or its research agencies. He offered Vicodin to one of them. He also attempted to get confidential information about Bristol-Myers Squibb’s FDA filing for a bipolar depression approval for rival drug Abilify, via a woman he was sleeping with. The deposition transcripts have been redacted to hide the identities of the women involved, but other documents in the case indicate that many of MacFadden’s colleagues had figured out that he was cheating on his wife with his work acquaintances. The redactions leave it unclear how many women he slept with, but it was at least two and perhaps as many as four, the documents show. What follows is a digest of quotes from the transcripts of various depositions and emails in the case. (Download some of the emails here.) The lawyers hoped to establish that the affairs constituted a conflict of interest that biased AZ’s science. MacFadden is first asked about his compensation. His salary was $185,000, plus $25,000 per year in bonuses, plus options. That came to in excess of $200,000 a year.

2009-03-15 @ 12:24:05 -->[bnet]