Alimta regimen didn't meet goal in study

Eli Lilly and Co. said Thursday a drug regimen including its Alimta therapy did not improve the survival of lung cancer patients in a late-stage clinical trial.

Lilly said patients who were treated with a combination of Alimta, Avastin, and the chemotherapy drug carboplatin lived for 12.6 months after the start of treatment. Patients who were treated with chemotherapy and Avastin, a drug that is made by Roche, had median survival of 13.4 months. There was not a statistically significant difference between the results of the two regimens.

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HIV Drug Reduces Transmission Among Men By Over 40%, Study Finds

A daily dose of antiretroviral medication lowered the risk of contracting HIV by more than 40% among men who have sex with men, according to a study published Tuesday in the New England Journal of Medicine, the New York Times reports.

The results of the study -- nicknamed iPrEx -- "are the best news in the AIDS field in years" and "could change the battle" against HIV/AIDS, according to the Times . Experts suspect the medication will be successful in other groups but caution that it must be tested first.

Details of Study

An international team of researchers enrolled 2,499 MSM at 11 sites in six countries to test a prevention strategy known as pre-exposure prophylaxis, which has been successful in preventing other diseases. The team was led by Robert Grant of the University of California-San Francisco Gladstone Institute of Virology and Immunology and Javier Lama of the Investigaciones Medicas en Salud in Lima, Peru . NIH and the Bill and Melinda Gates Foundation funded the study .

Half of the participants received a daily dose of Truvada, an antiretroviral drug containing emtricitabine and tenofovir, while the other half received a placebo. Both groups received counseling about condom use and safer sex practices. The researchers found that 36 participants taking Truvada contracted HIV, compared with 64 in the placebo group, representing a 43.8% reduction. They noted that the decrease was dependent on how frequently the subjects took the medication. Those who adhered to their medication at least half of the time experienced a 50.2% decline in risk, while those who took their medication at least 90% of the time saw a 72.8% risk reduction .

Caveats to Strategy

The researchers noted several limitations to the study, including that it only involved MSM and one combination of antiretroviral drugs. They said additional studies are under way to test Truvada in other high-risk groups, such as commercial sex workers and intravenous drug users, and heterosexual men and women.

Some HIV/AIDS advocates and scientists expressed concern about the cost of the strategy. Truvada costs between $12,000 and $14,000 annually in the U.S. Generic versions in developing countries cost as little as 40 cents per pill. They said they are also concerned that placing people on the drugs will speed the evolution of drug resistant strains of the virus or that people will stop using condoms .

Kevin Fenton, AIDS prevention chief at the Centers for Disease Control and Prevention, said that prophylaxis "should never be seen as a first line of defense against HIV," adding, "It's not time for gay and bisexual men to throw out their condoms" .

Grant said that the findings are "a major advance," but the strategy "will only work if people use it consistently, and the real challenge is how do you use it consistently" .

Advances in Preventive Approach

The findings follow this year's success with a vaginal microbicide gel and a proof-of-concept trial on an HIV vaccine . The microbicide study indicated that the gel protected 39% of all women testing it and 54% of those who used it consistently .

Alan Bernstein, health of the Global HIV Vaccine Enterprise, said, "This is a very exciting, dynamic time in HIV prevention research," adding, "There's clearly a growing realization that we're not going to be able to treat our way out of this epidemic" .

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Breastfeeding While Taking Seizure Drugs May Not Harm Childs IQ, Study Suggests

"While more research is needed with larger numbers of women and their babies, these results are reassuring to women who want to give their babies all the benefits of breastfeeding but also need to remain on their epilepsy medications to avoid devastating seizures," said study author Kimford Meador, MD, of Emory University in Atlanta and a Fellow of the American Academy of Neurology (AAN).

The study followed 194 pregnant women who were taking one epilepsy drug. Of their 199 babies, 42 percent were breastfed. When they were three years old, the children were given IQ tests.

The study found that there was no difference in IQ scores between the children who were breastfed and those who were not. Those who were breastfed scored 99 on the test, while those who were not scored 98, which is not a significant difference.

The women were taking the drugs carbamazepine, lamotrigine, phenytoin, or valproate. Meador noted that more research is needed on the effects of other, newer drugs for epilepsy. The children whose mothers were taking valproate had lower IQ scores, whether or not they were breastfed. American Academy of Neurology guidelines recommend that valproate be avoided during pregnancy due to risks of birth defects and effects on cognitive skills. AAN guidelines also recommend that women avoid taking more than one epilepsy drug at a time during pregnancy since taking more than one drug has been found to increase the risk of birth defects compared to taking only one medication.

Editorial author Autumn Klein, MD, PhD, of Brigham and Women's Hospital and the Harvard Medical School in Boston said that this is one of the first large studies on breastfeeding while taking an epilepsy drug.

"Many women are counseled not to breastfeed due to the lack of information on the effects of these drugs, but breastfeeding has many positive emotional effects for the mother and the baby along with the decreased risks for heart disease, diabetes, and obesity in the child and breast and ovarian cancer in the mother," Klein said. "This study highlights the pressing need for more data on epilepsy drugs in breast milk and the long-term effects."

The study was supported by the National Institutes of Health and the UK Epilepsy Research Foundation.

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No Link Between Heartburn Drugs and Birth Defects: Study

Babies born to women who took a popular class of heartburn drugs while they were pregnant did not appear to have any heightened risk of birth defects, a large Danish study finds.

This class of drugs, known as proton-pump inhibitors (PPIs), include blockbusters such as Prilosec (omeprazole), Prevacid (lansoprazole) and Nexium (esomeprazole). All were available by prescription-only during most of the study period (1996-2008), but Prilosec and Prevacid are now sold over-the-counter.

While the authors and an editorialist, publishing in the Nov. 25 issue of the New England Journal of Medicine, called the results "reassuring," experts still recommend using drugs as little as possible during pregnancy.

"In general, these are probably safe but it takes a lot of time and a lot of exposures before you see some of the abnormalities that might exist," explained Dr. Eva Pressman, professor of obstetrics and gynecology and director of maternal-fetal medicine at the University of Rochester Medical Center. "My recommendations are always to avoid medication exposure if at all possible. There are very few life-threatening disorders that require these PPIs," she noted.

"There are other ways to get the same effect," added Pressman, who was not involved in the study. "Most pregnant women have heartburn but most of it is relatively easy to treat with simple antacids such as Tums and Maalox and Mylanta, all of which are locally acting and absorbed, and don't pose any risk to the fetus."

Even propping yourself up so you're in a semi-vertical position, as opposed to lying flat, can help, said Dr. Michael Katz, senior vice president for research and global programs at the March of Dimes.

The research was funded by the Danish Medical Research Council and the Lundbeck Foundation.

The authors of the new study used linked databases to glean information on almost 841,000 babies born in Denmark from 1996 through 2008, as well as on the babies' mothers' use of PPIs during pregnancy.

PPI use by expectant women was the highest between 2005 and 2008, when about 2 percent of fetuses were exposed, but exposure during the critical first trimester was less than 1 percent.

Babies were followed until they were one year old.

The proportion of babies with birth defects hovered at about 3 percent in both groups -- 3.4 percent of those who had been exposed to a PPI in utero, and 2.6 percent for unexposed babies.

In an unexpected finding, there was a 39 percent increased risk of major birth defects among children whose mothers had taken PPIs in the month before conception, a finding the authors are attributing to either chance or to another factor, perhaps the reason the mother was taking the medication in the first place. This could have been infection with Helicobacter pylori, the bacteria that causes most ulcers.

In addition to Prilosec, Prevacid and Nexium, the authors also looked at Aciphex (rabeprazole) and Protonix (pantoprazole).

Prilosec was the only drug not associated with an increase in birth defects when taken during the month before conception, leading the editorial author to suggest this drug as a first line of treatment.

A related journal editorial, written by Dr. Allen A. Mitchell, director of the Slone Epidemiology Center at Boston University School of Medicine, also noted some caveats. These included the fact that even this big of a sample may not have been large enough to detect specific birth defects (such as heart defects) or to ascertain the effect of specific drugs within the class. Nor can the influence of other factors be ruled out, Mitchell wrote. Perhaps folic-acid supplementation during pregnancy is hiding the true effects of the PPIs, Mitchell said.

The bottom line, according to the experts, is that it's still not clear whether these drugs are safe or not for pregnant women.

"Having negative observations is never absolutely reassuring," Katz said. "All you can say is that within that range [in this case, 800,000 infants], the probability is that it is safe," he explained.

"The balance in pragmatic terms is how important is it to treat the symptoms that any drug is designed to treat versus the safety of pregnancy," he added. "That's a very difficult decision to make."

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Ticagrelor : New hope for heart attack patients

A major drug trial has brought scientists closer to making a drug that could prevent thousands of deaths from heart attacks.

From the past six years, international clinical trials have been going on a new drug, ticagrelor.

The new findings have revealed that the platelet function in patients taking ticagrelor recovered much quicker after the drug is stopped, compared to the current gold standard drug, clopidogrel.

This study has also confirmed that breathlessness occurs as a side effect of ticagrelor but this is not associated with any harmful effects on lung or heart function.

The findings also include a new analysis of a previous trial looking at ticagrelor.

This new examination of the Plato trial, which was completed last year, showed that ticagrelor prevents 1 in 5 deaths after a heart attack, and patients who develop the adverse effect of breathlessness with ticagrelor still benefit from a lower risk of death compared to patients treated with clopidogrel for one year following a heart attack.

This has also confirmed that patients treated with clopidogrel, who have a genetic variant that reduces the effect of this drug have a slightly higher risk following heart attack but ticagrelor is not affected by this variant and is still more effective than clopidogrel, regardless of a patient's genetic make-up.

The study has previously shown for every 1,000 patients treated for one year with ticagrelor instead of clopidogrel, there would be 14 fewer deaths or 11 fewer heart attacks without an increase in bleeding problems.

"The latest results on ticagrelor reinforce the positive data from the PLATO trial and suggest that ticagrelor has the potential to improve the quality of care and save many lives in the year following a heart attack, regardless of adverse effects or genetic differences in the response to clopidogrel," said Robert Storey of the University of Sheffield.

The latest findings were presented at the European Society of Cardiology (ESC) Congress 2010 and appeared in the Lancet.

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Rosuvastatin cuts risk of catching pneumonia, study finds

Patients taking AstraZeneca Plc’s cholesterol-lowering medicine Crestor (Rosuvastatin) in a study were less likely to develop pneumonia, a finding that potentially will broaden use of such drugs.

The result supports earlier research suggesting drugs in this class, called statins, prevent deaths from pneumonia. The latest study, an analysis of a 17,000-person clinical trial that ended in 2008, was presented today, in Boston, at the Interscience Conference on Antimicrobial Agents & Chemotherapy.

Cholesterol drugs, led by Pfizer Inc.’s Lipitor, were the world’s second-best-selling category of medicines last year, with $35.3 billion in sales, according to IMS Health Inc., a health research company in Norwalk, Connecticut. Only cancer drugs exceeded that tally. The latest Crestor finding justifies further research into giving statins to patients with lung disease, scientists said.

“These data are consistent with the hypotheses that statin therapy may reduce incident pneumonia,” supporting further study of the drugs to treat pulmonary disease, the researchers wrote.

Statins work by blocking an enzyme involved in cholesterol production in the liver. Results from a separate study in 2008 showed that people hospitalized with pneumonia were less likely to die if they took a statin. There is also evidence the drugs may help reduce inflammation, the formation of blood clots, and the immune system’s inappropriate attacks on healthy tissue.

Side-Effect Reports

The results released today come from an analysis of a study called Jupiter designed to show whether Crestor was more effective than a placebo at reducing cholesterol levels. Since the original study didn’t set out to measure the effect on pneumonia, researchers went back and examined reports collected during the trial to compare rates of pneumonia and other infections among those getting Crestor and those on a placebo.

The analysis found that 257 patients taking a placebo developed pneumonia compared with 214 patients taking Crestor, researchers said. Patients taking Crestor were also less likely to develop fungal, soft tissue or gynecological infections.

Crestor generated $4.5 billion in revenue last year for London-based AstraZeneca; Lipitor had sales of $11.4 billion.

Pneumonia kills about 52,000 people a year in the U.S., with the elderly and infants being most at risk, according to the Centers for Disease Control and Prevention, based in Atlanta.

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Novartis's Experimental Meningitis Vaccine Meets Goals in Late-Stage Study

Novartis AG said an experimental meningitis B vaccine met the goals of a late-stage clinical study.

The vaccine, called 4CMenB, achieved a “robust immune response” in the study of more than 3,600 infants, the Basel, Switzerland-based company said today in an e-mailed statement. The drug also had “an acceptable” side-effect profile, the company said.

Novartis expects the results of additional clinical trials over the next few months and plans to seek European regulatory approval for the vaccine by the end of 2010. The compound may be used in different age groups and alongside other vaccines, the Swiss drugmaker said. Infants are particularly vulnerable to the meningitis B virus which can kill within 48 hours of the first symptoms appearing, according to Novartis.

“Meningitis B can be devastating for affected families and is a major concern for pediatricians who care for children with this serious illness,” said Andrew Pollard, Professor of Pediatric Infection and Immunity at the University of Oxford. “Many cases of meningitis are prevented today by the vaccines we give to our children, but the more complex meningitis B remains as a major threat.”

Novartis pioneered the technology known as “reverse vaccinology’’ to develop the shot after decoding the genetic makeup of a pathogenic meningitis strain.

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Some patients with severe heart disease receiving wrong treatment, study finds

Tens or even hundreds of thousands of Americans are having coronary artery angioplasty and stenting every year when they should be having bypass grafts, and the result is an extra 5,000 or more deaths annually, researchers said Sunday.

Patients and cardiologists frequently prefer angioplasty and the insertion of a stent to keep arteries open because it is quicker and easier; patients go home sooner and return to work more quickly.

But new data from a major European-American study on more than 1,800 patients show that three years after the procedure, those who got stents were 28% more likely to suffer a major event, such as a heart attack or stroke, and 46% more likely to require a repeat procedure to reopen arteries. They were 22% more likely to die.

"This is one of the strongest studies yet demonstrating that, in advanced coronary disease, bypass has a real patient advantage," said Dr. Robert Guyton, chief of cardiothoracic surgery at the Emory University School of Medicine, who was not involved in the study.

"This will change practice," he said. "It may not reverse some of the use of stenting, but it is certainly going to slow it down and make people think. Stenting is a little bit easier on you and the return to work is quicker. But the benefits of surgery are more enduring and tend to emerge as time goes by."

Dr. Richard Shemin, chief of cardiac and thoracic surgery at UCLA's Ronald Reagan Medical Center, echoed that view. "Surgeons have had a strong feeling that, over time, surgery would be better for the most complex forms of heart disease," said Shemin, who also was not involved in the study.

The findings are "very strong, independent data that the public, payers and practitioners need to factor into how we make decisions in taking care of patients," he said.

"Any time that you compare angioplasty and surgery, the longer you go, the better surgery looks," said Dr. Michael J. Mack, first vice president of the Society of Thoracic Surgeons and a co-author of the study.

Coronary artery bypass grafts, commonly called CABG (pronounced cabbage), were the first treatment for blocked arteries. In the procedure, a blood vessel removed from elsewhere in the body, most often the chest or the leg, is used to bypass the blocked area, providing a new channel for blood to flow to the heart.

Hospital stays generally last five or six days, and the patient can return to work after a few weeks.

In recent years, however, cardiologists have turned more and more to balloon angioplasty, in which a catheter is threaded through a blood vessel in the groin to reach the blockage and a balloon is inflated at the site to compress the plaque. Originally, that was all that was done. Then physicians began inserting bare-metal stents, spring-like devices that hold the artery open.

More recently, doctors have begun using drug-eluting stents, which release a drug that helps prevent clot formation. Hospital stays are typically overnight, and the patient can return to work after a couple of days.

More than 1.3 million Americans now undergo angioplasty every year, compared with 448,000 who undergo bypass, according to the National Center for Health Statistics.

The new study, reported Sunday at a Geneva meeting of the European Assn. for Cardio-Thoracic Surgery, is the first large trial to compare stenting and CABG directly. Called SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), the trial enrolled 1,800 patients at 85 centers in Europe and the United States.

Patients were randomized to receive either angioplasty with stenting or bypass.

Patients were considered to have mild disease if they had a single blocked artery. Their disease was considered moderate or severe if they had a blockage in the left main artery — the primary artery supplying blood to the heart — plus blockage in one of the other three arteries, or if they had blockages in all three other arteries. They were also considered severe if they had very long blockages, arteries that were totally blocked, or "very tortuous, curvy arteries" that make angioplasty difficult, Mack said.

For patients with mild disease, the two procedures produced equivalent results, so angioplasty might be preferred because it is easier on the patient. Previous studies have also shown that such patients can be successfully treated with medical therapy alone. But the differences were much more dramatic for those with more severe disease, which is present in about half of all patients undergoing angioplasty in the U.S.

Dr. John Conte, associate director of cardiac surgery at Johns Hopkins Hospital in Baltimore, noted that it is now incumbent on physicians to make sure patients have all the facts before they undergo any procedure. "It's absolutely amazing that the federal government and private insurers don't insist on it," he said. "Wouldn't it make sense to do the right procedure the first time, rather than do it over and over and drive up the cost of healthcare? To me, it's a no-brainer."

By Thomas H. Maugh II, Los Angeles Times

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New drug hope for pancreatic cancer

A commonly used chemotherapy drug may offer a new lifeline to sufferers of one of the most deadly cancers, research has shown.

Trial results suggest that the drug 5-fluorouracil (5-FU) is an effective alternative for pancreatic cancer patients who fail to respond to standard treatment.

They also raise hopes of providing better therapy by combining the two drugs.

A study now under way is looking at the effect of prescribing a pill version of 5-FU with the more expensive standard chemotherapy drug, gemcitabine.

5-FU is currently used to treat a wide range of cancers including those affecting the bowel, breast and ovaries.

Almost 8,000 people are diagnosed with pancreatic cancer each year in the UK.

The disease is one of the hardest cancers to treat, and only around 3% of patients survive more than five years.

The new findings are published in the Journal of the American Medical Association (Jama).

Study leader Professor John Neoptolemos, director of the Liverpool Cancer Research UK Centre based at the University of Liverpool, said: "Until now the best way to treat pancreatic cancer has been unclear. But these results are the first to directly compare these two chemotherapies and show undoubtedly that they are both as effective as each other.

"Importantly this means patients now have a backup in case their cancer fails to respond to the first line of treatment. A new trial investigating whether combining these two treatments could be even more effective and prolong life is already under way and we look forward to seeing the result."

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Dutch study say that using Beta-Blockers is safe for Lungs

Medical tradition says that the beta blockers used to treat heart disease shouldn't be given to people who also have severe lung disease, but a new Dutch study suggests the tradition is wrong.

A study of more than 2,200 people with chronic obstructive pulmonary disease (COPD), a diagnosis that includes emphysema and chronic bronchitis, found better survival among those given beta blockers than those who did not get the drugs, claims a report in the May 24 issue of the Archives of Internal Medicine by physicians at University Medical Center Utrecht.

"To our knowledge, this is the first observational study that shows that long-term treatment with beta blockers may improve survival and reduce the risk of exacerbation of COPD in the broad spectrum of patients with a diagnosis of COPD," the researchers wrote.

"This is strikingly different from what our medical students are taught today," said Dr. Don D. Sin, a professor of medicine at the University of British Columbia in Vancouver, Canada, and co-author of an accompanying editorial. "Our traditional teachings are wrong."

The rap against beta blockers has been that while they improve heart function, they can cause airways to contract, a problem for people with COPD, Sin explained. "They demonstrate in this article that even people with COPD who use beta blockers did very well, better than people who didn't use beta blockers," he said.

Fears about beta blockers and COPD date back to the 1980s, when there were reports of "some nasty effects in patients with asthma, especially with high doses," said study author Dr. Frans H. Rutten, an assistant professor of medicine at Utrecht. The study demonstrates that the drugs can be handled safely for people with COPD, he noted.

"I know of no real problems now, especially when you start with a low dose so that the bronchial airways can adjust to the drug," Rutten said.

COPD was diagnosed in 560 patients at the start of the study in 1996, and 1,670 developed the condition by the end, in 2006. Of these, 665 were prescribed beta blockers for heart conditions, while 1,565 were not.

During an average follow-up time of 7.2 years, 27.2 percent of the people who took beta blockers died, compared to 32.3 percent of those not given the drug. The incidence of exacerbation -- severe flare-up -- of COPD was 42.7 percent among beta blocker users and 49.3 percent among nonusers.

The study isn't the final word on beta blockers and COPD, Sin said. That would have to come from a randomized, controlled study, which almost certainly will never be done, he said.

"If I had a heart attack, I wouldn't want to be in a clinical trial where there was a 50 percent chance I would get a sugar pill," Sin said. "So, this study may be the best evidence we get."

And the incentive of profit from increased use of beta blockers isn't there to have a drug company fund such a trial, since beta blockers are widely available in inexpensive, generic form, he added.

Sin acknowledged that he has been "an outlier" on the issue, already prescribing beta blockers for people with COPD. "But with this paper, I am much more confident that COPD patients can tolerate beta blockers," he said.

There are some exceptions, Sin noted. "For people with very bad asthma who have very reactive airways, I am much more cautious," he said. "I would start with the lowest dose possible, and then titrate upwards."

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Merck-Cardiome heart rhythm drug meets study goals

Merck & Co. and Cardiome Pharma Corp. said Friday that their drug candidate Brinavess met its goal in a late-stage clinical study, as it was better at restoring a steady heartbeat than an older drug use for the same purpose.

The trial compared Brinavess to the standard drug, amiodarone, as a treatment for atrial fibrillation. Atrial fibrillation is a condition in which the upper chambers of the heart beat rapidly and ineffectively. Merck and Cardiome said more than half the patients treated with Brinavess had a normal heart rhythm within 90 minutes, compared to about 5 percent of the amiodarone patients.

The companies said 51.7 percent of Brinavess patients had a normal heart rhythm within that time, and the median time to normal heart rhythm was 11 minutes. They said 5.2 percent of the patients who were treated with amiodarone met that goal. After 90 minutes, 53.4 percent of the Brinavess patients had no symptoms, compared to 32.8 percent of the amiodarone group.

Brinavess is an intravenous version of vernakalant, a drug Merck and Cardiome have been developing together. The companies have filed for approval in the U.S. and the European Union, and they are also working on an oral form of the drug. If approved, Brinavess would compete with Sanofi-Aventis' drug Multaq, which was approved in 2009.

A total of 232 patients were treated in the study, and Merck and Cardiome said the Brinavess patients also had a greater quality of life improvement based on a survey. The most common side effects of Brinavess were a bad taste in the mouth, coughing, sneezing, atrial fibrillation, nausea, dizziness, and high blood pressure.

Results from the trial were presented at a Heart Rhythm Society meeting in Denver.

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Trials begin on hepatitis C drug

The first human clinical trials have started on a new drug developed to treat infections caused by the hepatitis C virus.

The medication, taken orally, was first prepared at the Welsh School of Pharmacy at Cardiff University in 2008.

Laboratory tests showed it killed 90% of the virus at very low concentration.

Trials in healthy volunteers to assess the drug's safety are being held before its effectiveness on patients is tested in trials next year.

Approximately 170m people around the world are affected by hepatitis C, which can lead to liver cancer and cirrhosis and can be fatal.

It is the leading cause of liver transplantation in western countries.

The current treatment involves two drugs - ribavirin and interferon, which has to be given as an injection.

Side effects are often severe and lead to patients failing to complete the treatment.

However, researchers at the university believe the new drug, INX-189, is one of the most potent of its kind developed to date.

US pharmaceutical company Inhibitex, which owns the licence to INX-189 and has been working with the Cardiff team, is running the trials.

'Encouraging progress'

Professor Chris McGuigan, of the Welsh School of Pharmacy, who is the academic lead on the project, said the trials were in a "a very early stage".

"However, progress has been encouraging so far, going from the laboratory to human trials within 18 months.

"We believe that INX-189 offers the possibility of more potency against hepatitis, more rapid action in the liver, and fewer side effects than existing treatments."

Cardiff University and Inhibitex filed a patent on INX-189 earlier this year. It has been cleared for human clinical trials by the Food and Drug Administration in the US.

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Rotavirus vaccines reduce hospitalizations in kids

The introduction of the first rotavirus vaccine in the United States in 2006 led to sharp reductions in hospitalizations for gastroenteritis, an inflammation of the stomach and intestines that is marked by diarrhea and dehydration, researchers reported Wednesday. Rotavirus is one of the leading causes of gastroenteritis and was thought to be the cause of an estimated 55,000 to 70,000 hospitalizations in the United States each year before the introduction of the vaccine, Rotateq, in 2006 and the introduction of a second vaccine, Rotarix, two years later.

Epidemiologist Aaron T. Curns of the Centers for Disease Control and Prevention and his colleagues studied hospitalizations for gastroenteritis in 18 states accounting for almost 50% of the U.S. population. They compared rates for children hospitalized from 2000 to 2006 to those in the following two years. The team reported online in the Journal of Infectious Diseases that hospitalization rates for acute gastroenteritis dropped by 16% in 2007 and by 45% in 2008 compared with the earlier period. They estimated that about 55,000 hospitalizations were prevented during 2008 by the vaccinations, suggesting that the vaccine was highly effective at preventing most rotavirus cases.

The vaccines have been in the news recently because researchers have detected trace contamination of them by a pig virus that does not infect humans and that apparently causes no illness. In March, the Food and Drug Administration cautioned doctors against using the Rotarix vaccine because of the contamination. An FDA advisory panel earlier this month, however, said that both vaccines appeared safe and physicians should feel free to use them. The FDA has not yet issued a formal recommendation.

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Sanofi-Aventis Begins Study Of Heart Drug Multaq In 10,000 Patients For Expanded Use

Pharmaceutical company Sanofi-Aventis Wednesday said it has initiated a Phase IIIb trial of Multaq in over 10 thousand patients with permanent atrial fibrillation or abnormal heart rhythm. The Paris, France-based company’s study is focused on assessing the potential clinical benefit of the drug in reducing major adverse cardiovascular events, and it expects first patient enrollment to begin in the third quarter of 2010.

Multaq, or dronedarone, an antiarrhythmic drug, has completed clinical trials in more than 7,000 patients and has met the primary endpoint by reducing cardiovascular hospitalization or death by 24%. The company added that the incidence of atrial fibrillation is growing worldwide in relation to aging populations, increasing the risk of stroke up to five-fold, worsening the prognosis of patients with cardiovascular risk factors and doubling the risk of mortality.

The Phase IIIb study, dubbed PALLAS, is conducted primarily to demonstrate a reduction in major cardiovascular events like stroke, systemic arterial embolism, myocardial infarction or cardiovascular death. In addition, the study aims to lessen cardiovascular hospitalization or death from any cause among patients with permanent atrial fibrillation and additional risk factors.

The company said the secondary objectives are to evaluate the efficacy of Multaq in preventing cardiovascular death and to check whether the drug is well-tolerated in this patient population.

Stuart Connolly, MD, Division of Cardiology, McMaster University, Hamilton, Canada, one of the trial’s principal investigators commented, “This is a trial of major significance since no anti-arrhythmic drug has ever been shown to reduce major morbidity and mortality in permanent AF patients in a large scale clinical trial. We designed the PALLAS trial to further assess the role of Multaq(R) to reduce cardiovascular outcomes in patients with AF.”

Sanofi-Aventis elaborated that PALLAS is a multinational, randomized, double-blind, parallel-group, placebo-controlled, multicenter trial comparing the efficacy of Multaq 400mg twice-daily with placebo in permanent atrial fibrillation patients. The study of Multaq is expected to be conducted on 10,800 patients enrolled in 43 countries at 700 sites.

Multaq, discovered and developed by sanofi-aventis, was granted marketing authorization by the European Commission in November last year to treat adult clinically stable patients with a history of, or current non-permanent atrial fibrillation to prevent recurrence of atrial fibrillation or to lower ventricular rate.

Multaq is currently available in the U.S., Canada, Switzerland, Germany, Denmark, Ireland, Norway, Finland and the UK and is also being launched in most European countries in 2010.

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Additional Data From Phase 1b Study Of Hepatitis Drug Shows Positive Results

Biopharmaceutical company Achillion Pharmaceuticals Inc. said Tuesday that an additional preliminary data from its Phase 1b clinical trial of HCV Protease Inhibitor demonstrated positive results, with meaningful reductions in Hepatitis observed, and accompanied by continued safety and tolerability levels. Following the disclosure, the company's share were up 17.37% in the after hours trade.

Hepatitis C virus is the most common cause of viral hepatitis, an inflammation of the liver, and is currently estimated that more than 170 million people are infected with HCV worldwide.

ACH-1625 is an inhibitor of HCV NS3 protease that was discovered, and is being developed by Achillion. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures.

Now with the Phase 1b study, Achillon said the additional data revealed that both the third and fourth patient cohorts receiving treatment with ACH-1625 achieved meaningful reductions in HCV RNA after a five-day monotherapy.

Achillon said that results from its Third Dosing Cohort with 9 subjects, administered 200 mg twice daily over a 5 day period, showed a mean maximum reduction in viral load of 3.86 log10, compared with a mean rise of 0.16 log10 in the placebo group. Also, all subjects in the treatment group had a viral load decline greater than than 3.0 log10, and that there were no serious adverse events, and no clinically significant changes in vital signs, or laboratory evaluations. All adverse events in patients receiving ACH-1625 were classified as mild or moderate and were transient, with sustained viral suppression observed, the company added.

Further, the company said that the Fourth Dosing Cohort, with 8 subjects on a 600mg once daily dosage for five days, showed a mean maximum reduction in viral load of 3.81 log10 was achieved in the treatment group, compared with a mean rise of 0.24 log10 in the placebo group. Achillon stated that, all subjects in the treatment group had viral load decline greater than 3.0 log10, and that safety results were similar to those observed in previous segments of the trial. However, Achillon added, there was one non-drug-related serious adverse event, a bone fracture in a patient receiving placebo, but there were no clinically significant changes in vital signs, or laboratory evaluations. All reported adverse events in patients receiving ACH-1625 were classified as mild or moderate and were transient, with sustained viral supression observed.

Chief Executive Officer Michael Kishbauch said " It is impressive that at all dose levels ACH-1625 has shown meaningful viral load reduction and sustained viral suppression post treatment course. Importantly, we believe the results from these last two cohorts demonstrated that ACH-1625 was effective at a lower dosing level and in a once-daily dose, features that distinguish our drug and suggest it could offer improvements over other protease inhibitors currently in development.

If the results are sustained through further development, then ACH-1625 would contend as a potential best-in-class protease inhibitor, Kishbauch added.

Earlier, in Phase 1a safety studies with ACH-1625, where subjects were exposed to both single ascending dose, and multiple ascending dose, preliminary data demonstrated ACH-1625 was well tolerated at all doses and there were no serious adverse events, and no clinically significant changes in vital signs, and adverse events were classified as mild or moderate.

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Cleveland BioLabs Concludes Dosing of Second Safety Study for CBLB502

Cleveland BioLabs, Inc. Monday announced that dosing of healthy volunteers was completed in the second human safety study for CBLB502, a drug under development for the treatment of Acute Radiation Syndrome (ARS).

CBLB502 is being developed by Cleveland BioLabs under the U.S. Food and Drug Administration's Animal Efficacy Rule to treat ARS or radiation poisoning from any exposure to radiation such as a nuclear or radiological weapon / dirty bomb, or from a nuclear accident. This approval pathway requires demonstration of efficacy in representative animal models and safety, pharmacokinetic, pharmacodynamic and biomarker testing in healthy human volunteers.

Evidence of CBLB502's mechanism of action and activity in animal models was published in Science Magazine in April 2008 (Science, 2008, vol. 320, pp. 226-230). Data from 50 human subjects in an initial Phase I safety and tolerability study indicated that CBLB502 was well tolerated and that normalized biomarker results corresponded to previously demonstrated activity in animal models of ARS.

This second safety study included a total of 100 healthy human volunteers randomized among four dosing regimens of CBLB502. Participants in the study were monitored for adverse side effects and blood samples were obtained to assess the effects of CBLB502 on various biomarkers and to further characterize the pharmacokinetics of CBLB502.

Analysis of safety and biomarker data is ongoing. The primary objectives of this study are to gather additional data on safety, pharmacokinetics, and cytokine biomarkers in a larger and broader subject population in order to finalize an appropriate dose to take forward for the large, definitive human volunteer safety study.

The Biomedical Advanced Research and Development Authority (BARDA) of the Department of Health and Human Services supported the entire cost (approximately $1.3 million) of this clinical Phase 1b human safety study as part of contract HHSO100200800059C.

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Risks of some acid-reducing drugs may outweigh benefits

More than 113 million prescriptions are written every year for proton pump inhibitors, drugs such as Prilosec or Nexium that Americans take to treat ulcers or other problems affecting the stomach or esophagus. But more than half the time these acid-reducing drugs are overprescribed for less serious heartburn or indigestion, according to research cited in tomorrow's Archives of Internal Medicine.

The drugs do relieve stomach discomfort, but people who take them may be more likely to encounter other problems such as fractures or certain infections, three new studies say.

"For most patients the adverse effects of [proton pump inhibitors] outweigh the benefits," Dr. Mitchell Katz of the San Francisco Department of Public Health writes in an editorial.

Dr. JoAnn E. Manson of Brigham and Women's Hospital was part of a team that looked at the acid-suppressing drugs and broken bones related to osteoporosis among more than 161,000 older women enrolled in the the Women's Health Initiative. After eight years, women who took the drugs were no more likely to break their hips than women who didn't take the drugs. But they did have a 47 percent increased risk of spine fractures, a 26 percent increased risk of forearm or wrist fractures, and a 25 percent increased risk of other fractures. The authors advise doctors to periodically evaluate whether their patients should continue to take the drugs.

Two other studies consider whether proton pump inhibitors are linked to infections with Clostridium difficile, the leading cause of hospital-acquired diarrhea. Dr. Michael D. Howell of Beth Israel Deaconess Medical Center led a study that analyzed more than 100,000 admissions to the hospital. Patients who took proton pump inhibitors daily were 74 percent more likely than other patients to develop a C. difficile infection in the hospital, with the risk climbing higher with greater use of the drug.

In the other study, Dr. Amy Linsky of Boston Medical Center and her colleagues report on patients whose C. difficile infections recurred within 90 days. Among more than 1,100 patients treated at the New England Veterans Healthcare System, those who used proton pump inhibitors had a 42 percent higher risk of recurrence than patients who did not take the drugs.

Katz, who wrote the editorial, says doctors may want to ask their patient to try other ways to treat indigestion, such as eating smaller meals, losing weight, quitting smoking, reducing stress, or raising the heads of their beds at night. Or none of those. "Many cases ... resolve on their own," he writes.

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Ralfinamide fails in Serena study on NLBP patients

Newron Pharmaceuticals SpA, a research and development company focused on novel CNS and pain therapies, has announced that the topline top-line results of its Serena study, a phase-IIb/III study of ralfinamide in patients with at least moderate Neuropathic Low Back Pain (NLBP) failed to show any significant difference between ralfinamide and placebo.

The 12-week Serena study enrolled 411 patients with chronic NLBP of at least moderate severity and evaluated the safety and efficacy of two dose regimens of ralfinamide compared to placebo. Available results on the primary endpoint of the study, the change from baseline for the 11-point Likert Scale, did not detect any significant difference between ralfinamide and placebo. Ralfinamide was well tolerated, with no clinically significant differences from placebo on safety measures.

Further analyses of the additional endpoints (VAS, PGI, CGI etc) are currently ongoing and will be reviewed with Newron’s external advisors. Based on the multiple CNS effects seen in animal pharmacology models, and the excellent human safety data, Newron will decide how to proceed further with the compound.

Luca Benatti, Newron´s chief executive officer, commented, “We are extremely surprised and disappointed by the results, based on the statistically significant benefits shown in a phase II placebo-controlled trial, as well as the results from a large number of preclinical studies. We shall be working with our external advisors to make a complete assessment of the data prior to determining our next steps, including a review of our development resource needs going forward. We have a broad portfolio of products in various stages of development, addressing substantial market opportunities and this, combined with our existing cash resources and SEDA equity line, gives Newron continued potential for growth and value generation.”

In addition to ralfinamide, Newron has an advanced pipeline of innovative compounds, that include safinamide, currently in phase-III development for the treatment of Parkinson’s disease (add-on treatment for all stages of PD) together with Merck Serono; NW-3509, an novel treatment for schizophrenia expected to enter human trials later this year, and HF0220, a potential disease-modifying therapy for neurodegenerative disorders, currently in phase-II.

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Erectile dysfunction drug could enhance delivery of herceptin to brain tumours

A drug currently approved to treat erectile dysfunction could significantly improve the delivery of the anti-cancer drug Herceptin to certain hard-to-treat brain tumours, according to a new study at Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute.

The research could help doctors improve treatments for lung and breast cancers that have metastasized to the brain.

Even if a cancer is susceptible to drugs, these drugs must penetrate the “blood-brain barrier” if they’re to treat cancer that’s metastasised to the brain.

“Mother Nature created this barrier to protect our brains from dangerous substances, but here we need to get through the barrier to deliver the drugs, and that’s a problem,” says study author Dr. Julia Y. Ljubimova.

Dr. Keith Black, lead research scientist on this project, has studied the blood-brain barrier for about two decades.

Research conducted by his team found that the erectile dysfunction drugs sildenafil (Viagra) and vardenafil (Levitra), which inhibit the enzyme phosphodiesterase 5 (PDE5), could increase the permeability of the blood-brain tumour barrier and boost the effectiveness of the chemotherapy drug doxorubicin.

“No matter how effective against cancer a chemotherapeutic agent may be, it can have little impact on brain tumours if it cannot cross the blood-brain tumour barrier. As we find new drugs that are able to target these tumour cells, it is imperative that we develop better ways to enable the medications to reach their targets,” he said.

In the current study, the researchers examined whether PDE5 inhibitors might also increase the blood-brain tumour barrier’s permeability to Herceptin- a monoclonal antibody used to treat lung and breast tumours that are positive for HER2/neu.

Herceptin is a large molecule that does not easily cross the blood-brain tumour barrier, a limitation that severely reduces its effectiveness at treating brain metastases.

The researchers first measured vardenafil’s effects on the permeability of the blood-brain tumour barrier.

Using a mouse model, the scientists showed that vardenafil led to a two-fold increase in the amount of Herceptin that reached brain metastases of lung and breast cancers.

Next, they examined whether this increase in blood-brain barrier permeability improved Herceptin’s effectiveness at treating these brain metastases by giving mice vardenafil in tandem with Herceptin.

The results showed that the combination of vardenafil plus Herceptin boosted mean survival by 20 percent, compared to Herceptin alone (7218 days versus 599 days).

The study was published in the journal PLoS ONE.

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Drug-Eluting Peripheral Stent Continues to Show Positive Data at Two Years

Patients treated with the Zilver® PTX™ Drug-Eluting Peripheral Stent maintained clinical improvement at two years, according to interim results from the Zilver® PTX™ Global Registry presented today as a late-breaking clinical trial at the Society for Cardiovascular Angiography and Interventions (SCAI) 33rd Annual Scientific Sessions. The prospective, single-arm study is ongoing to evaluate the drug-eluting stent for the treatment of peripheral artery disease (PAD). Results of a separate pivotal randomized study in a similar cohort of patients are expected to be available later this year.

In the meantime, this analysis includes 12-month follow-up data from 721 patients and 24-month follow-up data from 447 patients who received the Zilver® PTX™ paclitaxel-coated stent in the superficial femoropopliteal artery (SFA), a major artery above the knee. The registry study was designed to evaluate stent integrity, event-free survival and freedom from target lesion revascularization.

PAD affects more than eight million people in the U.S. and, if not treated, can limit the ability to walk and exercise, as well as place patients at risk for limb loss. PAD patients also have a greater chance of heart attack, stroke and death.

Although use of DES is common in the coronary arteries, the peripheral arteries, including those in the legs, experience different types of stress caused by walking and other movement. In some instances, blockages in these arteries are very difficult to treat, and may ultimately lead to limb amputation. The study is the third to evaluate the effectiveness of a drug-eluting stent outside of the coronary arteries, but the first to suggest clinical efficacy. The Zilver® PTX™ is an investigational device.

The characteristics of the 787 patients who were enrolled and treated included restenosis of previously treated lesions in 24 percent, in-stent restenosis in 14 percent, and total occlusions in 38 percent; 22 percent of patients had lesions longer than 15 cm. The mean lesion length was 10.0 +/- 8.2 cm, the mean percent diameter stenosis was 84.6 +/- 16.4 percent, with an average of 2.2 Zilver® PTX® stents used per patient.

At 12 months, the event-free survival rate was 87.0 percent, and freedom from target lesion revascularization was 90.5 percent. X-ray evaluation found a very low rate of stent fractures, 1.5 percent of patients at 12 months. Patients available for 24-month follow-up had an event-free survival rate of 80.0 percent, and freedom from target lesion revascularization was 83.3 percent.

This low rate of target lesion revascularization translated into meaningful clinical improvement for the majority of patients, with both the average walking distance and average walking speed more than doubling following Zilver PTX stent implantation, and being sustained to two years. In addition there was a very good safety profile, and a very low rate of stent fractures.

"These interim data suggest this device is safe and efficacious for the treatment of SFA lesions," said William A. Gray, M.D., FSCAI, who presented the study data and is associate professor of clinical medicine and director of endovascular services at Columbia University Medical Center/New York Presbyterian Hospital. "Prior attempts to demonstrate drug-eluting stent effectiveness using sirolimus or its analogues have fallen short, but the use of a paclitaxel-coated, non-polymeric stent appears to have improved the outcomes for patients who received this study stent. If these results are confirmed in the separate randomized study using the same device, it will be welcome news to patients who suffer from this disease."

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