New Drug Boosts HCV Clearance

Most hepatitis C patients who are initially unresponsive to standard therapy were able to achieve sustained virologic responses when the investigational drug boceprevir was added, a researcher reported here.

Sustained responses were seen in 55% of patients receiving 44 weeks of boceprevir after showing no virologic response to four weeks of pegylated interferon-alfa-2b (PEGIntron) and ribavirin (Rebetol) in a Phase II trial, said Paul Kwo, MD, of Indiana University in Indianapolis.

Kwo, speaking here at the American Association for the Study of Liver Disease meeting, was reporting on two secondary analyses of data from the SPRINT-1 trial of boceprevir, an inhibitor of the hepatitis C virus (HCV) NS3 protease enzyme.

He had presented the main findings of the 520-patient study earlier this year at the European Association for the Study of the Liver meeting in Copenhagen.

Boceprevir is one of two HCV protease inhibitors in late-stage development, the other being telaprevir. (See DDW: Telaprevir Improves HCV Clearance in Resistant Patients) Phase III trials of both drugs are now under way.

In the SPRINT-1 trial, treatment-naive patients were randomized to five treatment arms, including one in which patients only received pegylated interferon and ribavirin, two involving immediate treatment with all three agents, and two in which boceprevir started after an initial, four-week lead-in with interferon and ribavirin.

All patients had HCV genotype 1a or 1b, mostly the former.

The secondary analyses reported here focused only this last treatment strategy, with patients receiving either 24 or 44 weeks of triple therapy following the four-week, two-drug lead-in.

Boceprevir was dosed at 800 mg three times a day.

In patients with no response to the lead-in -- defined as a reduction in HCV RNA loads of less than ten-fold -- 25% of those receiving boceprevir for 24 weeks still showed viral clearance after an additional 24 weeks of follow-up.

With 55% of initial null responders receiving the drug for 44 weeks showing long-lasting viral clearance, the longer therapy appeared to be more effective, Kwo said.

He also noted that boceprevir for both durations boosted response rates well above what would normally be expected from standard therapy in patients without strong responses in the first four weeks.

He cited results from an earlier large trial in which less than 5% of early nonresponders to standard therapy eventually developed sustained responses.

Among patients showing strong responses in the first four weeks of interferon and ribavirin, sustained responses were seen in most.

More than 80% of those with initial reductions of three to four orders of magnitude in viral RNA levels had sustained responses, as did nearly 100% of those with reductions of at least four orders of magnitude or whose viral RNA became undetectable in the first four weeks.

Duration of boceprevir treatment appeared to make no difference in sustained virologic response rates in these patients.

But Kwo cautioned that the findings in these analyses involved relatively small numbers of patients. Only about 50 patients were considered null responders to the lead-in treatment, and similar numbers had relatively strong initial responses.

Overall, adding boceprevir after the four-week lead-in led to sustained responses in 56% of patients receiving boceprevir for 24 weeks, and in 75% of those taking the drug for 44 weeks, Kwo said. Both response rates were significantly (P<0.01)>

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Vertex hepatitis C drug telaprevir works well in twice daily dosing

Vertex Pharmaceuticals Inc's closely watched hepatitis C drug telaprevir proved nearly equally effective in a twice daily regimen as three times a day, knocking out the virus in more than 80 percent of patients in both groups in a small study.

All previous Phase II studies of the highly promising experimental drug tested the medicine at three times a day dosing given at eight-hour intervals. This study hoped to show telaprevir could be administered twice a day 12 hours apart, which would be more convenient for patients.

Patients who received telaprevir twice a day in combination with the standard treatments of pegylated-interferon and ribavirin had a sustained viral response (SVR) of 82 percent in one arm and 83 percent in another, depending on which brand of interferon they received.

That compared with 81 percent and 85 percent of patients who were given telaprevir in the three times daily regimen, according to data to be presented at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston.

The percentage of patients in whom the virus is undetectable 24 weeks after completing treatment yields the critical measure known as sustained viral response, or SVR, which is considered tantamount to a cure.

"SVR rates of 75 to 80 percent (in twice daily dosing) would be very well received by investors," Sanford Bernstein analyst Geoffrey Porges said prior to release of the data.

"I was expecting around 70 percent," Dr Patrick Marcellin, the study's lead investigator, said in an interview.

"This is the highest we have observed with this triple therapy and the major conclusion is that the rate of SVR is similar in those patients who received bid (twice daily) and those who received it three times daily," said Marcellin, a professor of medicine at the University of Paris and head of Viral Hepatitis Research Center in Hospital Beaujon.

Importantly, Marcellin noted, even though the telaprevir dose was higher in the twice daily regimen, there were "no new side effects, and that is very encouraging."

Investors may also be encouraged by the low 3 percent dropout rate due to serious rash, which had been a source of some concern in earlier studies. Just four of 161 patients discontinued treatment due to rash, with another three pulling out due to anemia.

Marcellin said doctors have learned how to manage the rash and are now less likely to discontinue treatment as a result.

The open label study tested treatment naive patients, or those who had not received prior treatment for the serious liver disease. Treatment duration depended on how quickly patients responded to the medicines, an approach known as response-guided therapy.

Patients who achieved rapid viral response, defined as undetectable levels of virus at week four, and who maintained undetectable levels through week 20, were able to stop all treatment after 24 weeks of therapy -- 12 weeks on the three- drug combination and 12 more of standard therapy.

They were then followed for six months post treatment to determine whether they achieved SVR.

Eighteen percent of patients in the study did not meet that rapid response criteria and received a total of 48 weeks of treatment with the standard drugs.

Three percent of patients in the study relapsed during post-treatment follow-up, the company said.

"This study confirms that 24 weeks can be used in the large majority of patients with with high efficacy. Shorter duration means less side effects and better quality of life," Marcellin said, noting that "tailoring treatments according to the very early response improves the management of the patient and the chance of the patient to be cured."

There has been high hope that telaprevir will allow for 24 weeks of treatment for many patients. The current drugs must be taken for 48 weeks and are often difficult to tolerate, with many patients suffering flu-like symptoms for the duration.

"Many of these patients are relatively young and very active, so to treat shorter is a real benefit," Marcellin said.

He cautioned that this was a small study and that much larger Phase III clinical trials must confirm the results.

But he added: "As a clinician for our patients, this is an important hope for the future. This is a big step in the history of the treatment hepatitis C."

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Study finds stroke risk from anemia drug Aranesp

A new study raises fresh safety concerns about widely used anemia medicines, finding that the drug Aranesp nearly doubled the risk of stroke in people with diabetes and chronic kidney problems who are not yet sick enough to need dialysis.

The study is the largest ever of these blood-boosting drugs and the only one that compared them to a dummy treatment. The medicines have become blockbuster sellers because they lessen the need for transfusions, but their ability to prevent heart attacks, kidney failure or other problems have not been proven.

Over the last two years, the federal Food and Drug Administration has repeatedly strengthened warning labels on Aranesp, Epogen and Procrit as concerns rose that they may worsen survival in certain cancer patients, especially at higher doses. Amgen Inc. of Thousand Oaks, Calif., makes all three drugs, although New Brunswick, N.J.-based Johnson & Johnson sells Procrit.

The new study tested Aranesp in a different group of patients: 4,038 people with Type 2 diabetes, kidney problems and moderate anemia — problems that often go hand in hand. The goal was to see if the drug could prevent heart attacks, heart failure, strokes or the need for dialysis.

It not only failed to do that, but "we uncovered a risk that I think is substantial for stroke," said study leader Dr. Marc Pfeffer, a heart specialist at Brigham and Women's Hospital in Boston.

Strokes occurred in 101 patients given Aranesp and 53 patients given dummy shots. Looked at another way, the risk of suffering a stroke was about 1 percent per year in the placebo group and about 2 percent in those given Aranesp.

For many people, "this risk will outweigh its potential benefits," the study's authors conclude.

Results were published online Friday by the New England Journal of Medicine and were to be presented at a conference of kidney specialists in San Diego. Amgen sponsored the study. Pfeffer has consulted for the company and two authors work for it.

Dr. Roger Perlmutter, Amgen's head of research and development, said the magnitude of stroke risk "surprised us." The potential risk of stroke has been listed on Aranesp's label since the drug was approved in 2001, but "we will definitely update the label" because of the new study's results, he said.

Aranesp did reduce the need for transfusions — 297 people on the drug needed them versus 496 of those getting dummy shots. However, there was only a modest improvement in how fatigued people said they felt in the Aranesp group.

The study's results may not apply to people already on dialysis, Dr. Philip Marsden of St. Michael's Hospital and the University of Toronto in Ontario, Canada, writes in an editorial in the medical journal. For them, the quality of life improvement from fewer transfusions may be greater.

Also on Friday, the New York Attorney General's office said it and 15 states were suing Amgen, claiming the company gave kickbacks and weekend retreats to medical providers to help boost Aranesp sales, and encouraged them to bill third parties, including Medicaid, even though the drug was available to them at no cost.

A statement by the company said the allegations were "without merit."

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Weight Gain Associated With Antipsychotic Drugs

Young children and adolescents who take the newest generation of antipsychotic medications risk rapid weight gain and metabolic changes that could lead to diabetes, hypertension and other illnesses, according to the biggest study yet of first-time users of the drugs.

The study, to be published Wednesday in The Journal of the American Medical Association, found that 257 young children and adolescents in New York City and on Long Island added 8 to 15 percent to their weight after taking the pills for less than 12 weeks.

The patients, ages 4 to 19, added an average of one to one-and-a-half pounds a week.

“The degree of weight gain is alarming,” said Dr. Wayne K. Goodman, head of a Food and Drug Administration advisory panel on the drugs last summer and chairman of psychiatry at Mount Sinai School of Medicine in Manhattan. “The magnitude is stunning,” he said.

Although the drugs’ influence on weight and metabolism had been previously detected, Dr. Goodman, who was not involved in the study, said the speed and magnitude of the effects found in the study were greater than previously reported — findings he said were made possible by looking exclusively at new patients.

The four drugs in the study, the most popular antipsychotic medications, are industry blockbusters, with combined sales of $12.7 billion last year. And while all four caused weight gain, there were differences in the extent of the side effects. Among them, Zyprexa, made by Eli Lilly & Company, showed the most severe effects on weight and metabolism. The study’s authors, and an accompanying JAMA editorial, called for closer monitoring of patients taking the drugs, as well as additional long-term studies.

The drugs are prescribed for schizophrenia, bipolar disorder and a broad range of less serious psychological conditions. Their use by children and teenagers has been rising steadily. A 2008 study found that patients under 19 years old accounted for 15 percent of antipsychotic drug use in 2005, compared with 7 percent in 1996.

The study, financed by federal grants, is the largest yet published on childhood use of the drugs. And because it is also the largest study of first-time users of the drugs, whether children or adults, it provided an opportunity to analyze the cause and severity of near-term side effects.

As a result, the study goes further than previous research in distinguishing varying metabolic effects among the four drugs, according to Dr. Judith L. Rapoport, another expert who was not involved in the research.

“It’s by far the best documentation of not just weight gain and metabolic changes but also suggesting there might be differences among the drugs,” Dr. Rapoport, chief of the child psychiatry branch at the National Institute of Mental Health, said in an interview.

The lead researcher, Dr. Christoph U. Correll of Zucker Hillside Hospital in Queens and the Feinstein Institute for Medical Research in Manhasset, N.Y., said researchers had saved their blood work for future study of the molecular basis of the different drugs’ metabolic effects.

“People should think twice before they actually prescribe the medications,” Dr. Correll said in a phone interview. The drugs studied are in a class known as atypical antipsychotics, which are second-generation psychiatric drugs that in some cases regulate the receptors in the brain that interact with the mood-altering hormones serotonin and dopamine.

Abilify and Risperdal are the only two of the four drugs approved as pediatric treatments, for the severe mental conditions schizophrenia and bipolar disorder — and in Risperdal’s case, for some children with autism. More than 70 percent of atypical antipsychotics’ use in young children and teenagers has been off-label prescriptions for nonpsychotic conditions like attention deficit hyperactivity disorder, according to Stephen Crystal, a Rutgers University professor who studies the drugs.

Dr. Rapoport said Lilly’s Zyprexa drug, introduced in 1996, had been so heavily marketed that it was in widespread use before physicians began to recognize the severity of its side effects a few years ago. Zyprexa has continued selling in the range of nearly $3 billion a year in the United States even as concerns emerged about its tendency to cause patients to gain weight.

Abilify, from Bristol-Myers Squibb, showed the least metabolic effects among the four drugs in the study. “It’s considered a very good but weaker drug,” Dr. Rapoport said.

The other two drugs in the study, whose weight-related side effects fell between Zyprexa and Abilify, were Risperdal and Seroquel. Seroquel, from AstraZeneca, had United States sales of $2.2 billion in the first six months of this year, according to IMS Health, a research company. Abilify had sales of $1.9 billion during that period; Zyprexa, $1.5 billion; and Risperdal, from Johnson & Johnson, $660 million.

A Lilly spokesman, Jamaison R. Schuler, said the new research echoed Lilly’s own findings and previous studies about weight gain and metabolic changes that led to a label warning being placed on Zyprexa in October 2007. But in an interview, he said the drug was still essential to sparing children a lifetime of psychological suffering.

“It’s important to recognize that severe mental illnesses, including schizophrenia and bipolar 1 disorder, often strike during adolescence and are devastating,” Mr. Schuler said.

In an editorial accompanying the study in the journal, Dr. Christopher K. Varley and Dr. Jon McClellan, child psychiatrists at Seattle Children’s Hospital and the University of Washington school of medicine, wrote that “ominous long-term health implications” arise from weight gain and changes in blood fat levels early in life. “These results challenge the widespread use of atypical antipsychotic medications in youth,” they wrote.

Dr. Varley said in a phone interview Monday that doctors had been loath to use the older antipsychotic medicines, like Thorazine and Haldol, because of neurological side effects. But he said the new data indicated that the newer ones should be prescribed more cautiously.

“In the course of less than 12 weeks, the weight gains are startling,” he said. “If you look at Zyprexa, the kids are gaining a pound and a half a week. Even with the drug Abilify, which is one that was not so prone to weight gain, kids still gained a pound a week. In addition, they had evidence in a very short period of time of other metabolic problems.”

The study covered 272 patients visiting clinics in Brooklyn, Queens and Long Island from 2001 to 2007. Fifteen patients who stopped taking their medicine were used as a control group. Their weight stayed level. The 257 patients who stayed on their drugs took detailed tests, including a fasting blood test to check for high glucose levels.

Their mean weight at the start of the study period was 118 pounds. But after about 11 weeks, those who took Zyprexa had gained 18.7 pounds; Seroquel, 13.4 pounds; Risperdal, 11.7 pounds; and Abilify, 9.7 pounds.

Their waists typically expanded three inches with Zyprexa, and two inches with the others.

All but Abilify showed rapid and significant increases in one or more metabolic markers, which can presage adult obesity, hypertension and Type 2 diabetes. The metabolic markers included glucose, insulin, triglycerides and cholesterol.

The authors noted that the study had limitations. Patients were not randomly assigned, so the baseline starting weights differed. Clinicians, given the choice, started heavier patients on Seroquel and those with the lowest fat mass on Zyprexa, who then gained the most, the data show. Also, the study did not control for dosing or other medications, which can affect outcome.

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New Drug May Offer Hope to Some With Lung Cancer

Maintenance therapy with the drug pemetrexed improves the survival of people with non-small-cell lung cancer whose disease has not progressed after chemotherapy, a new study has found.

Nearly 90 percent of all people who die from lung cancer have non-small-cell tumors. At the time the cancer is discovered, it's considered advanced about 40 percent of the time, according to background information in a news release from The Lancet, which is publishing the study. Chemotherapy reduces the tumors in just 40 percent of advanced cases, it said.
The phase 3 study included 663 people in 20 countries who had an advanced stage of the cancer but no disease progression after four cycles of platinum-based chemotherapy. They were randomly selected to be given pemetrexed or a placebo in 21-day cycles.

The cancers did not progress for 4.3 months, on average, in people in the pemetrexed group, compared with 2.6 months in the placebo group, the study found. People given pemetrexed survived an average of 13.4 months, compared with 10.6 months for those given the placebo.

That means that those in the pemetrexed group had a 50 percent reduction in the risk for disease progression or death and a 21 percent reduction in the risk of death only, the researchers said.

Drug-related toxic effects caused discontinuation of treatment in 5 percent of the pemetrexed group and 4 percent of the placebo group. No deaths were found to be related to pemetrexed, according to the study.

"Pemetrexed maintenance therapy is well tolerated and offers significantly improved progression-free and overall survival compared with placebo, making it a new treatment option for patients with advanced non-squamous, non-small-cell lung cancer who do not progress after initial induction therapy," Dr. Chandra Belani, of the Penn State Hershey Cancer Institute, and her colleagues concluded.

The study, which appears online and in an upcoming print issue of The Lancet, was released Sept. 19 to coincide with the European Cancer Organization meeting.

Dr. Thomas Stinchcombe of the Lineberger Comprehensive Cancer Center at the University of North Carolina, and Dr. Howard West, of the Swedish Cancer Institute in Seattle, wrote in an accompanying editorial that the use of pemetrexed as maintenance therapy "merits being considered as a strong option, reflected by the recent approval of pemetrexed in this setting by the European Medicines Agency and the U.S. Food and Drug Administration."

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Heartburn drugs don't interfere with Plavix

Heartburn pills like Nexium and Prilosec do not stop blood-thinning drugs such as Plavix from working effectively, contrary to recent fears, new research on Monday showed.

The finding is reassuring to patients, doctors and drug companies, including AstraZeneca and Sanofi-Aventis, who make the blockbuster treatments.

Plavix is the world's second biggest-selling medicine, with worldwide sales of around $9 billion, while Nexium revenues totaled $5.2 billion in 2008.

Plavix, also known as clopidogrel and sold by Sanofi and Bristol-Myers Squibb, is widely used with proton pump inhibitors, or PPIs, including AstraZeneca's Nexium and Prilosec to cut the risk of gastric problems.

A study in March raised concerns that mixing the two types of medicines increased the risk of heart patients having a second heart attack and led regulators on both sides of the Atlantic to issue warnings discouraging combined use unless essential.

But Michelle O'Donoghue of Boston's Brigham and Women's Hospital said a new analysis of a large clinical involving more than 13,000 patients taking Plavix or Eli Lilly and Daiichi Sankyo's new drug Effient, or prasugrel, showed they did not interfere with the heart drugs' clinical benefits.

"Use of a proton pump inhibitor was not associated with increased risk of cardiovascular events for patients on either clopidogrel or prasugrel," she told the annual meeting of the European Society of Cardiology.

The most commonly used PPIs in the study were Prilosec and pantoprazole.

O'Donoghue's findings will be published in the Lancet medical journal on Tuesday.

Lars Wallentin of the Uppsala Clinical Research Center in Sweden told doctors in Barcelona he had also seen no evidence of PPI-associated problems in a study involving more than 18,000 patients that compared Plavix and AstraZeneca's experimental drug Brilinta.

Cardiologists said the new analyses were encouraging. Many had worried that avoiding PPIs would lead to more gastrointestinal bleeding complications.

However, the issue will only be closed conclusively by conducting a large clinical trial focused specifically on interaction, said Kurt Huber, a cardiologist at Wilhelmine Hospital in Vienna.

"There seems to be no deleterious effect ... but we need a prospective randomized trial to definitely establish safety," he told the meeting. "As long as we don't have these data, careful selection of patients who need gastric protection should be performed."

Source : www.reuters.com

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FDA criticizes Genzyme study of leukemia drug

Just days before a key meeting to consider Genzyme Corp.’s application for a new leukemia drug to treat older patients, the Food and Drug Administration released a briefing document criticizing the Cambridge biotechnology company’s clinical study of the drug, called Clolar.

Genzyme said the drug deserves to be approved to treat adult acute myeloid leukemia in people who aren’t healthy enough to undergo chemotherapy, citing results of its study involving patients over 60 years old.

The company said it found older patients with the disease had a 45.5 percent overall remission rate when they took the treatment.

Clolar, the brand name for the drug clofarabine, won FDA approval in 2004 to treat a different form of leukemia - cancer of the blood or bone marrow - in patients under 21 who have had relapses after undergoing chemotherapy. Genzyme filed a new drug application Nov. 21 for older patients with acute myeloid leukemia.

The company and the FDA are scheduled to present their findings Tuesday to an outside panel of specialists, called the Oncological Drug Advisory Committee, which will make a recommendation. Such recommendations are typically followed by the agency.

But in the briefing document posted on the FDA’s website yesterday, regulators said Genzyme didn’t follow the agency’s guidance in designing its Phase II clinical study. While the FDA had advised the company to conduct a “randomized’’ study, comparing patients who took Clolar with those who underwent an alternative treatment or took a so-called sham drug, the company ran a “single-arm’’ study consisting only of patients who used Clolar.

The regulatory feedback suggests the FDA believes “this study was poorly conceived,’’ said Ira Loss, health care analyst for Washington Analysis, a research firm advising institutional investors on regulatory trends. “My strong sense is that the committee will recommend against approving the drug for this indication.’’

Shares of Genzyme, which has been working to get production problems at its Allston Landing plant under control, slid $1.37, or 2.4 percent, to $55.53 yesterday on the Nasdaq exchange.

Beth Trehu, product general manager for clofarabine at Genzyme, said the company wanted to run a randomized study, it was unable to get physicians to agree on a “comparative’’ treatment for the population of older patients with acute myeloid leukemia.

Nonetheless, said Trehu, “we think our study shows a very positive benefit/risk ratio, a very positive response rate, and very durable remissions. We’re hoping the [oncology] panel will recommend approving our drug based on its efficacy and safety.’’

Source : www.boston.com

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New drug may cut risk of stroke by one-third

People at risk of stroke may, for the first time, be offered a potentially superior alternative to the blood-thinning drug warfarin, following the publication of a major drugs trial yesterday.

The RE-LY study compared the effectiveness of warfarin with a new drug, dabigatran, in over 18,000 people at risk of having a stroke due to a common heart rhythm condition called atrial fibrillation.

The Canadian-led researchers found dabigatran reduced the risk of stroke by 34 per cent compared to patients taking warfarin, without increasing the risk of major bleeding.

The results, published online by the New England Journal of Medicine and presented to the European Society of Cardiology Congress in Barcelona yesterday, suggest doctors will be able to offer patients an alternative to warfarin, which is highly effective within a narrow dose range, but requires regular monitoring to check its effectiveness and to prevent the risk of unwanted bleeding.

According to Professor Stuart Connolly, director of the Division of Cardiology at McMaster University in Canada, a lead investigator of the study, “several new drugs have been recently studied to see if they could replace warfarin. None, however, has been satisfactory.”

“Either they were not effective enough, they had too many side- effects or they caused too much bleeding.

“This is the first time in more than 50 years that a new oral blood thinner has been developed which has been found to be both safer and more effective than existing therapy,” said Dr Connolly.

Atrial fibrillation is the most common heart rhythm condition, affecting about 1 per cent of the total population, rising to 10 per cent in people over the age of 80.

People with the condition have an increased risk of blood clots, which in turn raises the risk of developing a stroke. About one in six strokes are caused by atrial fibrillation.

The RE-LY study was carried out in more than 951 centres in 44 countries. Patients were enrolled over a two-year period and followed up for one further year.

The results found a higher dose of dabigatran (marketed under the trade name Pradaxa), at 150 mg twice daily, significantly reduced the risk of stroke by 34 per cent compared to warfarin.

The lower dose, 110 mg twice daily, had a similar effect to warfarin in the prevention of stroke, but with significantly less major bleeding.

Source : www.irishtimes.com

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Teen trippin' on ADHD drugs can be a real downer

Calls to poison control centers about teens abusing attention-deficit drugs soared 76 percent over eight years, sobering evidence about the dangerous consequences of prescription misuse, a study shows.

The calls were from worried parents, emergency room doctors and others seeking advice on how to deal with the problem, which can be deadly. Four deaths were among cases evaluated in the study.

Kids taking ADHD drugs to get high or increase alertness may not realize that misuse of the drugs can cause serious, sometimes life-threatening symptoms, including agitation, rapid heartbeat, extremely high blood pressure.

"They say, 'It's FDA approved, how dangerous could it be?'" said Steve Pasierb, head of The Partnership for a Drug-Free America, based in New York.

In the study, researchers from Cincinnati Children's Hospital Medical Center evaluated 1998-2005 data from the American Association of Poison Control Centers. During that time, nationwide calls related to teen abuse of ADHD drugs, specifically stimulants, increased from 330 to 581 yearly, and there were four deaths. Overall, 42 percent of teens involved had moderate to severe side-effects and most ended up getting emergency-room treatment.

The true number of teen abusers who have bad side effects is likely much higher, because many cases don't result in calls to poison control centers, said study author Dr. Randall Bond, medical director of the hospital's Drug and Poison Information Center.

The surge, from 1998 to 2005, outpaced calls for teen substance abuse generally. It also paralleled an 86 percent rise in ADHD medicine prescriptions for kids aged 10 to 19, from about 4 million to nearly 8 million during that time.

"It's more bad news on an entrenched problem," Pasierb said. His nonprofit group was not involved in the study. Its own research suggests that about 19 percent of teens have abused prescription drugs including medicine for attention deficit hyperactivity disorder.

Government-sponsored surveys suggest that teen abuse of stimulants including ADHD drugs has declined in recent years.

The new study was for release Monday in the August edition of Pediatrics.

Mark Stein, a psychiatry professor and ADHD expert at University of Illinois at Chicago, said abuse typically involves crushing and snorting the pills, which speeds up the effects and can produce a buzz or sense of euphoria — along with dangerous side effects.

Kids who develop serious side effects should be taken to the emergency room, where sedatives can be used to treat the problem, Stein said.

The study lacks information on whether abusers were teens with ADHD, but anecdotal evidence suggests many are not.

Stein said the study should not deter use of ADHD drugs in teens who really need them, particularly since there's evidence that kids with ADHD who don't get medication are at risk for abusing illicit drugs.

Source : www.newsday.com

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New drug-resistant TB strains could become widespread says new study

The emergence of new forms of tuberculosis could swell the proportion of drug-resistant cases globally, a new study has found. The finding raises concern that although TB incidence is falling in many regions, the emergence of antibiotic resistance could see virtually untreatable strains of the disease become widespread.

Australian researchers from the University of New South Wales and the University of Western Sydney have published the new finding in the latest issue of the Proceedings of the National Academy of Sciences.

Laboratory-based studies have suggested that antibiotic-resistant TB strains cause longer-lasting infections but with a lower transmission rate. Therefore, scientists have questioned whether drug-resistant TB strains are more likely than drug-sensitive strains to persist and spread – an important question for predicting the future impact of the disease.

One in three humans already carries the TB bacterium. Although it remains latent in most cases, the World Health Organisation (WHO) has estimated there were 9.27 million new cases of TB in 2007. There were 1.6 million TB-related deaths in 2005. Drug-resistant TB is caused by inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period or because the drug supply is unreliable.

A research team led by UNSW's Dr Mark Tanaka used epidemiological and molecular data from Mycobacterium tuberculosis strains isolated from Cuba, Estonia and Venezuela to estimate the rate of evolution of drug resistance and to compare the relative "reproductive fitness" of resistant and drug-sensitive strains.

"We found that the overall fitness of drug-resistant strains is comparable to drug-sensitive strains," says Dr Tanaka of the Evolution and Ecology Research Centre. "This was especially so in Cuba and Estonia, where the there is a high prevalence of drug-resistant cases."

The finding may reflect an inconsistency in drug treatment programs in these countries. Indeed, Estonia now has one of the highest rates of multi-drug resistance in the world. The intermittent presence of drugs and the resulting transmission of resistant strains would have let drug-resistant strains collectively spend more time within untreated hosts, allowing them to evolve ways to become more infectious and out-compete the drug-sensitive strains.

The study also reveals that the contribution of transmission to the spread of drug resistance is very high – up to 99 per cent – compared with acquired resistance due to treatment failure. "Our results imply that drug resistant strains of TB are likely to become highly prevalent in the next few decades," says UNSW's Dr Fabio Luciani, the study's lead author. "They also suggest that limiting further transmission of TB might be an effective approach to reducing the impact of drug resistance."

"Mathematical and statistical methods can add a lot of value to empirical data by allowing us to account for the processes behind them," says research co-author, Dr Andrew Francis from the University of Western Sydney. "In this case, we use samples of TB genotypes, together with information about drug resistance, to make inferences and predictions that wouldn't have been possible just a few years ago."

Source : www.eurekalert.org

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Genzyme rival gets positive test results

British drug maker Shire PLC stepped up the pressure on Cambridge biotechnology company Genzyme Corp. yesterday, reporting positive test results for a competitor to Genzyme’s drug for Gaucher disease and disclosing that US regulators will let doctors prescribe the rival drug before it is approved for commercial use.

Supplies of Genzyme’s enzyme replacement therapy Cerezyme, currently the only drug on the market to treat the rare genetic disorder, were interrupted in June when a virus was detected in the company’s Allston Landing plant.

While the plant resumed production last week after the decontamination of its bioreactors, Genzyme, the state’s largest biotechnology company, will continue rationing drugs to the least vulnerable patients until late this year, when new batches of the drugs can be shipped and inventories return to their full strength.

Shire’s competing drug, velaglucerase alfa, could be administered to some Gaucher disease patients in a matter of weeks, following Food and Drug Administration approval of a company plan for introducing the drug, called a treatment protocol. The agency solicited the protocol, a relatively uncommon arrangement that allows doctors to prescribe drugs for up to 12 months before they have received FDA approval. A treatment protocol is typically reserved for situations such as supply disruptions, where there are acute medical needs.

The early rollout of Shire’s drug could give the company a leg up in its efforts to grab a share of the market for Gaucher disease treatments. But the company had planned to submit a new drug application to the FDA even before Genzyme’s supply interruption.

“We’re just responding to the patient need at this point, which is what matters most,’’ said Sylvie Gregoire, the president of Shire’s human genetic therapies division in Lexington, which produces velaglucerase alfa, and other enzyme replacement drugs. “That’s what the FDA wants. If this turns into an opportunity for us, that’s fine.’’

Genzyme officials declined to comment yesterday. The company’s shares shed 2.91 percent, or $1.51, to $50.38 on the Nasdaq exchange. It was the second consecutive session of retreat for Genzyme shares, pushing its stock down 10.8 percent since Thursday.

The first drop came Friday, when the company disclosed that federal in spectors will be paying another visit to the Brighton facility because of concerns that previously identified production problems there hadn’t been “fully or adequately’’ addressed by Genzyme.

Shares of Shire, meanwhile, edged up 0.65 percent, or 29 cents, to $45.10 in Nasdaq Composite trading yesterday.

Gaucher disease is an enzyme deficiency in which fatty substances accumulate in the spleen, liver, lungs, bone marrow, and sometimes, the brain, causing bruising, enlarged organs, and lung and kidney ailments. It affects only about 5,700 people worldwide. But the treatment for it, which is often subsidized by governments or insurance companies, costs approximately $200,000 per year per patient, bringing the potential market for drug makers to about $1.2 billion.

In addition to Shire, two other drug companies, Actelion Pharmaceuticals Ltd. of Switzerland, and Protalix BioTherapeutics Inc. of Israel, are developing drugs to treat Gaucher disease.

Genzyme is likely to keep the lion’s share of the market in the near future, but finds itself under increasing regulatory and competitive pressure, said Christopher J. Raymond, senior biotechnology analyst for financial services firm Robert W. Baird & Co. in Chicago.

“They’ve had a string of setbacks,’’ Raymond said of Genzyme, citing the FDA inspection and the intensifying competition. “The situation has deteriorated since we first learned about the problems in Allston. I still have the utmost confidence they will get these problems fixed, but there’s a risk that the FDA might not get back in the plant on a timely basis or might find something else that they don’t like.’’

On the competitive front, Shire, which has nearly 1,000 employees in Lexington and Cambridge, yesterday reported positive results from the first of three phase 3 studies of veraglucerase alfa.

The data were consistent with previous studies that helped convince the FDA to accept the company’s treatment protocol that will allow doctors to prescribe the drug before it wins final approval by the agency.

Shire said it began a “rolling submission’’ of its new drug application last Wednesday, three weeks after it received fast-track designation from the FDA. The designation enables companies to file sections of the application as they become available, and allows the agency to review those sections before the entire application is filed. Shire said it expects to complete the application by Sept. 30.

Source : www.boston.com

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New drug could reduce prescription prices for heart patients

Heart patients who need to take a prescribed daily regimen of medicine to prevent blood clots might find lower prescription prices in an area that has been monopolized for years.

Dr. Shereif Rezkalla, an interventional cardiologist at Marshfield Clinic, recently took part in a worldwide, independent study that examined the effectiveness of a new drug, Prasugrel, which prevents platelets in the blood from sticking together.

The study found the medicine to be as effective as Plavix, the only similar drug on the market.

Rezkalla said Prasugrel's potency is important, but a major bonus is that it should help force down the price of Plavix, through competition for market share.

Plavix costs about $155 for 30 pills for a person without insurance.

"I know many patients of mine who needed (Plavix) and couldn't take it because of their financial budget," Rezkalla said. "It just became very expensive, and some patients truly have to pick between medications and their regular food."

Rezkalla said Prasugrel won't be cheap, particularly because the study found that it appears to be slightly more effective. Seven percent of patients taking Prasugrel had nonfatal heart attacks, compared to 9.1 percent taking Plavix.

Plavix is prescribed daily, Rezkalla said, but many patients struggle to afford it. While he's excited about the medical breakthrough, he said it's more important for patients if Prasugrel can lead to lower costs.

"I get more excited when I know to my patient it will be less of a burden on him financially," he said. "It's a problem I don't see once in a while or occasionally, but almost every day."

Both medicines are used to prevent clots that can lead to heart attacks or strokes and are necessary in patients undergoing angioplasty, Rezkalla said.

A small amount of the population is resistant to Plavix, making Prasugrel useful as another tool to combat clotting. Rezkalla said there are no firm data that estimate the number of people who are resistant to Plavix.

The most serious side effect, because of its potency, is that people who take Prasugrel are more prone to bleeding, Rezkalla said. Older people and those with a low body weight should avoid taking it.

The Federal Drug Administration recently approved the medicine and Rezkalla said Prasugrel, which he administered to patients at Saint Joseph's during the study, should be available within the next month. It will be marketed as Effient.

Source : www.wisconsinrapidstribune.com

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Threat of resistance to artemisinin-based anti-malarial drugs highlighted by new study

Malaria parasites in western Cambodia have become resistant to artemisinin-based therapies, the first-line treatment for malaria, according to a study published in the New England Journal of Medicine today. Resistance to the drugs makes them less effective and could eventually render them obsolete, putting millions of lives at risk.

Signs of artemisinin resistance have been reported in the region already, but this new research is the first detailed study of the problem. The study was funded by the Wellcome Trust, the Li Ka Shing Foundation, and the Global Malaria Programme of the World Health Organisation (through grants from the Bill and Melinda Gates Foundation and the Western Pacific Regional Office).

Malaria is a potentially deadly disease that kills more than a million people each year, mainly young children and pregnant women. It is caused by malaria parasites, which are injected into the bloodstream by infected mosquitoes. The most deadly form, Plasmodium falciparum, is responsible for nine out of ten deaths from malaria.

The most effective anti-malarial drug is artemisinin, derived from Artemisia annua, also known as sweet wormwood, which had been used in Chinese medicine for centuries under the name Qinghaosu. It was rediscovered in the 1970s, evaluated first in South-East Asia, and eventually accepted as an essential component of antimalarial treatment in the past few years. The artemisinin derivatives have the advantage over other anti-malarial drugs, such as chloroquine and mefloquine, in having few side effects and – until now – malaria parasites have no resistance against it.

Although the drugs – most commonly in the form of the derivative artesunate – can be used on their own as a monotherapy, fears over the possible development of resistance mean that they are usually given in conjunction with one or more other drugs as artemisinin-based combination therapies (ACTs), now recommended by the WHO as the first-line treatment for uncomplicated falciparum malaria in all endemic countries.

Following increasing reports that the efficacy of artemisinin monotherapies and combination therapies were declining in western Cambodia, researchers at the Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Programme, based in Bangkok, studied the susceptibility of P. falciparum parasites to the drugs. The Research Programme is a collaboration between Mahidol University, Bangkok, and the University of Oxford, supported by the Wellcome Trust.

The researchers studied forty patients in each of Pailin, western Cambodia, and Wang Pha, north-western Thailand. In two open-label, randomised trials, each was given the relevant dosage appropriate to their body weight of either artesunate or a combination of artesunate and mefloquine.

On average, patients in Thailand were clear of parasites in 48 hours; in western Cambodia this took 84 hours – in other words, it took almost twice as long to clear the parasites in Cambodia as it did in Thailand.

During the treatment period, as the number of parasites in the blood falls, so the infection should clear. Its recurrence can be a sign that the drug treatment is not working effectively.

In this study, out of the twenty patients treated with the monotherapy in each country, there were recurrences of the infection in six patients in western Cambodia compared to just one person in Thailand. Of the twenty patients treated with the combination therapy, infection recurred in two patients in Cambodia compared to one in Thailand. These results again suggest that artemisinin was less effective on the Cambodian parasites.

"Our study suggests that malaria parasites in Cambodia are less susceptible to artemisinin than those in Thailand," says Dr Arjen Dondorp, lead author of the study. "This means that it takes longer to kill the parasites. Artemisinin should clear the parasites at an early stage, preventing them further maturing and reproducing. When the drug's action is impaired, it becomes more difficult to eliminate the parasites from the body.

"With artesunate losing its potency, ACTs rely much more on the weaker partner drug, increasing the risk that resistance also evolves towards the partner drug. This has very important consequences for the lifespan of ACTs. Losing ACTs would be a disaster for malaria control."

Artemisinin-based drugs have been in use in western Cambodia for around thirty years and the country was one of the earliest to switch to ACTs in 2001. However, the majority of patients in the region receive their medication from the private sector, which is less well regulated. Patients in the private sector are frequently provided with monotherapies or incomplete treatment courses. Added to this is the problem of substandard or counterfeit drugs with sub-clinical doses of artemisinin. This extended period of sub-optimal use of artemisinin-based drugs may have contributed to the emergence of resistance.

With signs of artemisinin-resistance occurring in other areas of Cambodia and Thailand, Dr Dondorp says swift action is required to contain the spread.

"Preventing the spread of resistant parasites when they emerge is crucial," he says. "The use of combination therapies is very important for this. I would like to see a ban on artesunate monotherapy except for specific cases."

Professor Nick White, co-author of the study and Chair of the Wellcome Trust South-East Asia Programme, believes the implications of the findings are potentially huge.
"Artemisinins are essential weapons in our war against malaria," he says. "If they become ineffective, we have no immediate replacement. The consequences could be devastating. Elimination of malaria will not be possible and millions of lives could be lost."

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Asthma drug may increase risk of heart attack and stroke

After a post-marketing study suggested a disproportionate increase in heart attacks and strokes in patients treated with Xolair (omalizumab), compared to those who were not given the drug, the U.S. Food and Drug Administration (FDA) announced last week that it is conducting a safety review.

Xolair, a drug administered by injection every other week, is manufactured by Genentech and co-marketed by Novartis and was approved by the FDA in June, 2003 to treat patients at least 12 years old with moderate-to-severe persistent allergic asthma unresponsive to inhaled steroids.

The study, begun in 2004 and conducted by San Francisco-based Genentech Inc., is an observational study of 5000 patients who took Xolair and 2500 who did not. Because it is not a randomized trial, which is considered by researchers to be the gold standard in determining cause and effect, its conclusions may have built in bias. For example, there could be differences in underlying risk factors for heart attack and stroke between the two study groups, making it difficult for the FDA to ultimately decide how to act on the information. Patients and their doctors have to deal with even greater uncertainty since neither the drug company nor the agency is making public the data that generated the alert.

An FDA Early Communication available online states that it “is in keeping with the FDA’s commitment to inform the public about its ongoing safety reviews of drugs”. While the investigation is still under way, the agency is not telling doctors to stop prescribing Xolair and is not recommending any changes to the prescribing information for Xolair. However, doctors and patients are being advised to report side effects from the use of Xolair to the FDA's MedWatch Adverse Effects Reporting program. Once its review is completed, the finding should be communicated to the public along with any resulting recommendations.

This issue with Xolair points out some of the problems with newly approved drugs. While all new drugs go through clinical testing to demonstrate safety and efficacy prior to approval by the FDA for sale in the United States, these premarket clinical trials involve relatively small numbers of individuals compared to the actual numbers who will eventually take the drugs. As a result, it is impossible to really know how the drug might affect the general population until it is widely used. As more and more drugs have been getting accelerated approval, the FDA has required postmarketing study commitments in writing from drug manufacturers to learn additional information about the risks, benefits and optimal use of an approved drug. About half of new drug applications approved in fiscal years 1990 through 2004 involved at least one postmarketing study commitment, according to the Department of Health and Human Services Office of Inspector General (OIG). Postmarketing study results often lead to labeling changes, such as new warnings or dosing instructions. Xolair is one such drug and the manufacturer seems to be following through on its commitment.

However,despite their many promises, pharmaceutical companies often fail to submit required annual status reports to the FDA about postmarketing drug safety and efficacy studies and unfortunately, regulators lack the authority to punish those companies. In a 2006 report, the OIG attributed failed oversight to a lack of manpower and resources at the FDA.

According to OIG, 35% of the 336 annual status reports that were or should have been submitted by drug makers in fiscal year 2004 were missing entirely or contained no information on postmarketing study commitments. About 40% of these reports were missing one or more items of required information, investigators added.

FDA reported in the March 3 Federal Register that drug companies in fiscal year 2005 had missed the deadline for submitting 47% of their annual status reports. The agency also reported that 65% of open postmarketing studies had not been started as of September 2005.

After the 2006 report, the FDA promised to do better regulation of the postmarkeing process. Nevertheless, according to a Bloomberg report, data released by the agency in 2008, indicated that drugmakers had made little progress in beginning studies they had promised to conduct after their products were approved. According to the FDA 62 percent (1044), of incomplete studies for drugs and biotechs had yet to be started as of Sept. 30, 2008. At the same time in 2006, 63 percent (1026), of the unfinished studies hadn’t begun.

Source : www.examiner.com

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Exenatide Once Weekly Provided Superior Glucose Control Compared To Lantus in Head-to-Head DURATION-3 Study

Amylin Pharmaceuticals, Inc. , Eli Lilly and Company and Alkermes, Inc. today announced positive results from a study comparing subjects randomized to either exenatide once weekly or Lantus® (insulin glargine). Patients randomized to exenatide once weekly experienced a statistically superior reduction in A1C, a measure of average blood sugar over three months, of 1.5 percentage points from baseline, compared to a reduction of 1.3 percentage points for Lantus after completing 26 weeks of treatment.

At the end of the study, patients treated with exenatide once weekly achieved a mean A1C of 6.8 percent compared with a mean A1C of 7.0 percent in those treated with Lantus. Treatment with exenatide once weekly also produced a statistically significant difference in weight, with a mean weight loss of 5.8 pounds at 26 weeks, compared with a mean weight gain of 3.1 pounds for Lantus, a difference of 8.9 pounds between the treatments.

In addition, although patients treated with exenatide once weekly experienced a greater reduction in blood glucose than those treated with Lantus, they also reported significantly fewer episodes of confirmed hypoglycemia.

These intent-to-treat results were from DURATION-3, the third in a series of studies designed to test the superiority of exenatide once weekly, an investigational diabetes therapy, as compared to other diabetes medications. This 26-week open-label, clinical study compared exenatide once weekly to once-daily doses of Lantus in 467 patients with type 2 diabetes taking stable doses of metformin alone or in combination with a sulfonylurea. Exenatide once weekly was administered once a week in a fixed dose while Lantus was administered daily in a variable dose determined by patient blood sugar levels.

“Exenatide once weekly outperformed Lantus in this superiority study by meeting its primary endpoint,” stated Orville G. Kolterman, M.D., senior vice president of research and development, Amylin Pharmaceuticals. “Both treatment arms started with a baseline A1C of 8.3 percent and exenatide once weekly provided statistically significantly greater A1C reduction, weight loss versus weight gain and fewer episodes of hypoglycemia.”

More than 90 percent of patients completed the study. During the 26-week treatment period, the most frequently reported adverse events were upper respiratory infection, including nasopharyngitis, in both treatment arms, as well as gastrointestinal events, including nausea, in the exenatide once weekly treatment group. Patients treated with exenatide once weekly experienced less confirmed hypoglycemia; the incidence of hypoglycemia was 4 percent with exenatide once weekly versus 19 percent with Lantus for patients on metformin background therapy, and 20 percent with exenatide once weekly versus 44 percent with Lantus for patients on metformin and a sulfonylurea background therapy, differences that are statistically significant in both treatment groups.

Study Design

The 26-week open-label, superiority study included 467 subjects with type 2 diabetes who were not achieving adequate glucose control using metformin therapy alone or in combination with a sulfonylurea. Subjects were randomized to receive exenatide once weekly 2 milligrams by subcutaneous injection weekly or insulin glargine injections administered daily in a variable dose determined by patient blood sugar levels. There was no lead-in or wash-out period. The primary endpoint was reduction in A1C; secondary endpoints included change in body weight along with other parameters of glucose control, cardiovascular health, hypoglycemia and patient-reported outcomes. Subjects in both treatment groups are continuing in an open-ended extension study.

The companies plan to present the full data set at a major medical meeting and submit the data for publication.

About Diabetes

Diabetes affects more than 23 million people in the U.S. and an estimated 246 million adults worldwide.(i,ii) Approximately 90-95 percent of those affected have type 2 diabetes. Diabetes is the fifth leading cause of death by disease in the U.S. and results in approximately $174 billion per year in direct and indirect medical expenses.(iii)

According to the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey, approximately 60 percent of people with diabetes do not achieve their target blood sugar levels with their current treatment regimen.(iv) In addition, 85 percent of type 2 diabetes patients are overweight and 55 percent are considered obese.(v) Data indicate that weight loss (even a modest amount) supports patients in their efforts to achieve and sustain glycemic control.(vi,vii)

About Amylin, Lilly and Alkermes

Amylin, Lilly and Alkermes are working together to develop exenatide once weekly, a subcutaneous injection of exenatide for the treatment of type 2 diabetes based on Alkermes' proprietary technology for long-acting medications. Exenatide once weekly is not currently approved by any regulatory agencies.

Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. Amylin's research and development activities leverage the Company's expertise in metabolism to develop potential therapies to treat diabetes and obesity. Amylin is headquartered in San Diego, California.

Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help healthcare professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Indiana, Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.

Alkermes, Inc. is a fully integrated biotechnology company committed to developing innovative medicines to improve patients' lives. Alkermes' robust pipeline includes extended-release injectable, pulmonary and oral products for the treatment of prevalent, chronic diseases, such as central nervous system disorders, addiction and diabetes. Headquartered in Cambridge, Massachusetts, Alkermes has research facilities in Massachusetts and a commercial manufacturing facility in Ohio.

This press release contains forward-looking statements about Amylin, Lilly and Alkermes and the investigational drug, exenatide once weekly. Actual results could differ materially from those discussed or implied in this press release due to a number of risks and uncertainties, including the risk that exenatide once weekly may be affected by unexpected new data; safety and technical issues; clinical trials, including the clinical trial mentioned in this press release, not being completed in a timely manner, not confirming previous results, or not achieving the intended clinical endpoints; the DURATION-3 superiority study results potentially not being predictive of real world use including results relative to other diabetes medications; pre-clinical trials not predicting future results; label expansion requests or New Drug Application (NDA) filings, not being submitted in a timely manner; regulatory approval, including approval for exenatide once weekly, being delayed or not received; or manufacturing and supply issues. The potential for exenatide once weekly may also be affected by government and commercial reimbursement and pricing decisions, the pace of market acceptance, or scientific, regulatory and other issues and risks inherent in the development and commercialization of pharmaceutical products including those inherent in the collaboration with and dependence upon Amylin, Lilly and/or Alkermes. These and additional risks and uncertainties are described more fully in Amylin's, Lilly's and Alkermes' most recent SEC filings including their Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Amylin, Lilly and Alkermes undertake no duty to update these forward-looking statements.

Source : www.drugs.com

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New Data from Phase III SATURN Study Showed Tarceva Improved Overall Survival When Used Immediately After Initial Chemotherapy in Patients with Advanc

OSI Pharmaceuticals, Inc. and Genentech, Inc. today announced that SATURN, a pivotal Phase III study of Tarceva® (erlotinib), met a key secondary endpoint of extending overall survival in patients with advanced non-small cell lung cancer (NSCLC) who received Tarceva immediately after initial chemotherapy. A statistically significant improvement in overall survival was seen in this pre-planned final analysis of the total patient population. The new data will be presented during the 13th World Conference on Lung Cancer to be held July 31 to August 4, 2009 in San Francisco.

Treating patients immediately following first-line chemotherapy versus waiting for the cancer to grow or spread before giving additional treatment represents a new approach in advanced NSCLC.

“This study has now not only confirmed that immediate treatment with Tarceva after initial chemotherapy delayed the progression of disease, but also importantly helped patients in the study live longer,” said Professor Federico Cappuzzo, M.D., Istituto Clinico Humanitas IRCCS, Milan and principal investigator of the SATURN study. “This is good news for doctors and their patients since advanced lung cancer is one of the most challenging cancers to treat and is often associated with a very short life expectancy.”

The overall survival data will be submitted to the U.S. Food and Drug Administration (FDA) to support the supplemental New Drug Application (sNDA) for use of Tarceva as a first-line maintenance treatment for patients with advanced NSCLC that was submitted on March 17, 2009. The FDA Prescription Drug User Fee Act (PDUFA) review date will be on or about January 18, 2010.

Additionally, Roche, OSI's international collaborator for Tarceva, will submit the overall survival data to the European Medicines Agency (EMEA) to support the application for use of Tarceva as a first-line maintenance treatment submitted in March 2009.

The U.S. and EU submissions were based on positive data from SATURN that were presented at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) on May 31, 2009 in Orlando, Fla. SATURN met its primary endpoint and showed patients with advanced NSCLC who received Tarceva as a first-line maintenance treatment had a 41 percent improvement in the time they lived without the disease advancing (progression-free survival or PFS) compared to placebo (hazard ratio=0.71; 29 percent reduction in the risk of cancer progression or death). The safety results were consistent with what has been seen previously and there were no new or unexpected safety signals in the study. The most commonly reported adverse events in patients who received Tarceva were rash (49 percent, 213/438) and diarrhea (20 percent, 88/438).

According to the American Cancer Society, lung cancer is the leading cause of cancer death in the United States. In 2009, approximately 159,000 Americans will die from the disease. Most people are diagnosed with advanced stage disease and only 15 percent survive five years.

Source : www.drugs.com

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Atrial-Fibrillation Patients Have Increasing Options for Treatment

The irregular heartbeat known as atrial fibrillation is one of the toughest heart conditions to treat. Drugs aimed at restoring a normal beat are often ineffective and can have serious side effects. The anticoagulants that many people with A fib, as it’s known, need to take can react with other drugs and raise the risk of bleeding.

Now, alternatives are increasing: A new drug was approved this month, and a relatively new surgical procedure is growing in popularity. But their long-term benefits are still unclear, some doctors say.

“We all groan when we get a patient with A fib,” says Dara Lee, a cardiologist at Presbyterian Heart Group in Albuquerque, N.M.

Atrial fibrillation occurs when the heart’s upper chambers—the atria—beat erratically. Blood can stagnate and clot in these chambers, and some clots can travel to the brain, causing strokes. People with the condition also have a higher risk of developing heart failure. In many people, atrial fibrillation isn’t life-threatening. But it can cause symptoms such as palpitations, shortness of breath and fatigue.

There is enough confusion about treating the condition that the Institute of Medicine, a National Academy of Sciences branch that advises the government on health issues, recently recommended atrial fibrillation as a top priority for federally funded research into the best treatments.

For doctors, a key dilemma is whether to try to return the heart to a regular beat. Doing so can relieve symptoms, but there is little evidence that it reduces the risk of stroke, according to William Maisel, a cardiologist at Beth Israel Deaconess Medical Center in Boston. Also, the anti-arrhythmia drugs traditionally prescribed for this purpose don’t work in many patients, doctors say, and can have bad side effects. Patients who take amiodarone, one widely used treatment, can develop pulmonary fibrosis, which causes scarring in the lungs. Sometimes, amiodarone can also make an irregular heartbeat worse.

In some patients, doctors instead try to slow down the irregular heartbeat with beta blockers or calcium-channel blockers. An influential 2002 study showed that this strategy may have advantages. Patients who were treated with the aim of restoring a normal heartbeat didn’t live longer than those whose irregular heartbeats were merely slowed down. Also, they were hospitalized more often than the latter group and suffered more side effects from their drugs.

The U.S. Food and Drug Administration this month approved for sale the first new anti-arrhythmia drug in many years: Multaq, from Sanofi-Aventis SA. In a trial of 4,600 people with atrial fibrillation, the drug reduced a patient’s risk of death or hospitalization due to cardiovascular problems when compared to a placebo pill. The drug, also known as dronedarone, carries a black-box warning that it shouldn’t be used in patients who have recently had severe heart failure, because it can cause severe problems including death.

Dr. Lee said she would like to see research comparing Multaq to amiodarone to help her decide which is a better bet. Dr. Maisel said there are some indications that Multaq may have fewer side effects. “I don’t know that it offers a huge advantage, but it offers another alternative,” he said.

Surgical procedures are giving doctors more options. In radiofrequency catheter ablation, a long, flexible tube is fed through the groin or neck to the heart, where it delivers electrical pulses that destroy small areas of tissue responsible for generating the irregular heartbeats.

The procedure has been used on only a small proportion of patients, but the drawbacks of drug therapy have “really started causing a migration of patients to ablation therapy,” says David Brown, a cardiologist and professor at SUNY-Stony Brook School of Medicine.

The procedure has been shown to help patients maintain a normal heart rhythm for up to a year, but little is known about its long-term effects, an agency of the Department of Health and Human Services said this month, calling for more research.

Source : online.wsj.com

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Earlier death due to new drug

Schizophrenia patients given a cheap older drug are less likely to die prematurely than people on newer treatments, despite the older product's well-known adverse side effects, Finnish researchers said on Monday.

The finding may lead to wider use of clozapine - sold by Novartis as Clozaril, but also available as a generic - instead of newer drugs like AstraZeneca's Seroquel, the current market leader.

Clozapine was the first of a new generation of schizophrenia drugs, known as atypical antipsychotics. But its use has been restricted by health authorities because of safety concerns and patients taking it require regular blood tests.

Despite this, an analysis of 10 years' records for 67,000 patients in Finland found that, compared to treatment with the first-generation drug perphenazine, the risk of early death for patients on clozapine was reduced by 26 per cent.

By contrast, mortality risk was 41 per cent higher for those on Seroquel, known chemically as quetiapine; 34 per cent higher with Johnson & Johnson's Risperdal, or resperidone; and 13 per cent higher with Eli Lilly's Zyprexa, or olanzapine.

'We know that clozapine has the highest efficacy of all the antipsychotics and it is now clear, after all, that it is not that risky or dangerous a treatment,' study leader Jari Tiihonen of the University of Kuopio said in a telephone interview.

'We should consider whether clozapine should be used as a first-line treatment option.'

Mr Tiihonen estimates clozapine is given to around one fifth of Finnish schizophrenia patients, but less than 5 per cent in the United States.

Clozapine's side effects include agranulocytosis, a potentially fatal decline in white blood cells, and current rules stipulate the drug can only be used after two unsuccessful trials with other antipsychotics.

Mr Tiihonen and colleagues wrote in the Lancet medical journal that these restrictions should be reassessed in the light of their findings, since not using the drug may have caused thousands of premature deaths worldwide.

Seroquel, Zyprexa and Risperdal are among the world's top-selling drugs, with a combined sales of US$12.5 billion (S$18.3 billion) in 2008, although Risperdal now faces generic competition.

Source : www.straitstimes.com

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Obesity emerges as new risk factor for severe flu

People who are obese but otherwise healthy may be at special risk of severe complications and death from the new H1N1 swine flu virus, U.S. researchers reported on Friday.

They described the cases of 10 patients at a Michigan hospital who were so ill they had to be put on ventilators. Three died. Nine of the 10 were obese, seven were severely obese, including two of the three who died.

The study, published in advance in the Centers for Disease Control and Prevention's weekly report on death and disease, also suggests doctors can safely double the usual dose of oseltamivir, Roche AG's antiviral drug sold under the Tamiflu brand name.

"What this suggests is that there can be severe complications associated with this virus infection, especially in severely obese patients," said CDC virus expert Dr. Tim Uyeki.

"And five of these patients had ... evidence of blood clots in the lungs. This has not been previously known to occur in patients with severe influenza virus infections," Uyeki said in a telephone interview.

Dr. Lena Napolitano of the University of Michigan Medical Center and colleagues studied the cases of 10 patients admitted to the university's intensive care unit with severe acute respiratory distress syndrome caused by infection with H1N1.

"Of the 10 patients, nine were obese (body mass index more than 30), including seven who were extremely obese (BMI more than 40)," they wrote in their report.

Their study was not designed to see if obesity or anything else poses a special risk factor for flu. But the researchers were surprised to see that seven of the 10 patients were extremely obese.

Multiple Organ Failure

Nine had multiple organ failure, which can be seen in influenza, but five had blood clots in the lungs, and six had kidney failure.

None has fully recovered, the researchers said.

The H1N1 swine flu virus first emerged in Mexico in March and was spreading out of control in the United States by the time it was identified at the end of April. The World Health Organization declared a pandemic in June.

While it is causing moderate illness, all influenza viruses can be deadly and this one is no exception. It has killed close to 500 people globally, more than 200 in the United States alone.

However, the new virus has a slightly different pattern from seasonal flu -- it spreads in the summer months, attacks young adults and older children, and may affect the body slightly differently.

As with H5N1 avian influenza, which only rarely attacks people, patients seem to survive better if they get extra-high doses of Tamiflu for longer than the usual 10-day treatment course, Uyeki said.

"We don't know if it is necessary for a higher dose of the drug to be given to patients who are obese," he said.

"The high prevalence of obesity in this case series is striking," the CDC's commentary accompany the report reads.

"Whether obesity is an independent risk factor for severe complications of novel influenza A (H1N1) virus infection is unknown. Obesity has not been identified previously as a risk factor for severe complications of seasonal influenza."

Source : www.reuters.com

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New Nanoparticles Could Revolutionize Therapeutic Drug Discovery

A revolutionary new protein stabilisation technique has been developed by scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) which could lead to 30 per cent more proteins being available as potential targets for drug development - opening up exciting possibilities in drug discovery.

Understanding the structure of proteins is a vital first step in developing new drugs, but to date, drug development has been slowed because due to their instability, proteins are difficult to work with in lab conditions. However, using nanoparticles, scientists from the Universities of Birmingham and Warwick have found a way to preserve membrane proteins intact, enabling detailed analysis of their structure and molecular functions.

These new findings, which have just been published online in the Journal of the American Chemical Society, will give scientists access to previously ignored proteins deemed too unstable to work with.

Professor Michael Overduin, from the University of Birmingham, who led the study, explained: "We have shown how a polymer can wrap around and preserve membrane proteins intact in stable nanoparticles. Membrane proteins are the most valuable but technically challenging targets for drug discovery. Finding a gentle solution that preserves their structure and activity, yet is robust enough for experimental interrogation, has eluded scientists for decades, but is now available."

Using a polymer - styrene maleic acid lipid particles (SMALPs), the researchers solubilised a pair of membrane proteins. They found that not only did the proteins maintain their folded structure, binding and enzyme activities in the SMALPs, but also that using the nanoparticles allowed them to be simply and rapidly used for virtually any laboratory analysis.

Advantages of SMALPs over traditional ways to solubilise proteins such as detergents include enhanced stability, activity and spectral quality of the protein membranes.

Dr Tim Dafforn who jointly ran the study, said: "In the past, studies have concentrated largely on soluble proteins as membrane proteins are so difficult to make. However, the discovery of the SAMLPs removes this barrier and opens up access to membrane proteins - this has exciting clinical implications as it may enable drug discovery on receptors that are currently too difficult to produce or study by current methods."

Commenting on the findings, BBSRC Chief Executive Professor Doug Kell, said: "The attrition rate in developing new drugs is phenomenal. Only a tiny fraction make it into the clinic to benefit patients. Research such as this that can help to increase the number of potential targets will mean a larger pipeline for scientists to develop new drugs from and, ultimately more, better drugs for patients. Fundamental bioscience working in coordination with medical research is vital to deliver new, effective drugs."

Source : www.sciencedaily.com

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