Selective PDE4 inhibitor is aimed at patients with severe COPD associated with chronic bronchitis.

The European Commission granted Nycomed marketing authorization for Daxas® (roflumilast). The drug is indicated as an add-on to bronchodilator therapy for maintenance treatment of severe COPD (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations.

Daxas reportedly represents the first new class of treatment for COPD in more than a decade. It is a selective phosphodiesterase 4 (PDE4) enzyme inhibitor. It is taken as an oral tablet once a day and is expected to be launched in European countries, starting with Germany and the U.K.

On April 26, Nycomed and Merck & Co. signed an agreement to co-promote Daxas in France, Germany, Italy, Spain, Portugal, and Canada. Nycomed will manufacture and distribute the finished product in all these countries. In addition, the two companies entered into an exclusive distribution arrangement for the commercialization of Daxas in the U.K. Nycomed will supply finished product and has retained a co-promotion option. For the U.S. the company signed a collaboration and distribution agreement with Forest Laboratories in August 2009. The NDA for Daxas was submitted in July 2009.

“Daxas is a novel therapy that improves lung function and most importantly reduces exacerbations,” says Klaus F. Rabe, M.D., lead author on various Daxas clinical trials from the University Medical Centre in Leiden, The Netherlands. “It has a unique mode of action that targets the underlying inflammation in COPD and is an important addition to the current options available to doctors and patients.”

Neil Barnes, M.D., professor of respiratory medicine at Barts and the London Hospital and Nycomed consultant, notes, “We have a large number of patients who remain symptomatic and have frequent exacerbations despite existing treatments, and for that more severe end of the spectrum we need new therapeutic options. The main additional benefit of Daxas on top of what is already achieved with bronchodilators is to reduce the number of exacerbations, or flare ups.”

The application to the EMEA was based on four Phase III trials in symptomatic COPD patients. In two placebo-controlled, 12-month studies involving over 3,000 patients, Daxas demonstrated statistically significant improvements on both co-primary endpoints: moderate-to-severe exacerbations and prebronchodilator FEV1.

The effect of Daxas was independent of concomitant use of long-acting beta2-agonist, according to Nycomed. In two supportive studies the drug also showed a statistically significant improvement compared to placebo on lung function over a six-month period when added to the bronchodilators tiotropium or salmeterol. Full data from all four studies was published in The Lancet in August 2009.

Source: GEN

Popularity: 3% [?]

An extensive study into the merits of screening men between the ages of 50 and 65 for prostate cancer has found it can cut death rates from the disease by as much as half, Swedish scientists said Thursday.

But the findings don’t necessarily mean nationwide prostate screening programs should introduced, experts said, since they run the risk of significant overdiagnosis of tumors in men who would not have suffered any harm from their cancer.

Researchers from the University of Gothenburg conducted a trial involving 20,000 men who were divided equally into a group that was offered prostate screening and a group that was not.

The screening method used was so-called prostate-specific antigen (PSA) testing, which is widely used in the United States and other developed countries to detect early signs of tumors.

Over 14 years of follow-up, prostate cancer death rates were cut almost by half in the screening group compared with the non-screening group, as men were diagnosed and treated in time to stop the cancer from killing them.

Jonas Hugosson, who led the study, said the results showed that PSA screening of all men this age group “can result in a relevant reduction in cancer mortality.”

Screening for cancer — or for clues such as pre-cancerous cells — is strongly encouraged in wealthy nations as a way of improving public health. But there are growing doubts about whether the screening’s benefits always outweigh the negatives, with the main concerns centering on the risk of overdiagnosis.

A large U.S. study published last year found that routine prostate screening has resulted in more than 1 million American men being diagnosed with tumors who might otherwise have suffered no ill effects from them. In that study, researchers said that around 20 men had to be diagnosed and treated for every one who benefited.

In the Swedish study, which was published in The Lancet medical journal Thursday, the researchers said the risk of overdiagnosis was less, but still 12 men needed to be diagnosed to save one life.

Prostate cancer is the second most common cancer in men after lung cancer, killing around 254,000 men a year around the world. U.S. doctors have routinely recommended PSA screening in men over 50 based on the assumption that early diagnosis and treatment is better than standing by and doing nothing.

But fears about overdiagnosis, which can lead to treatments such as surgery, radiation or hormone therapy that can cause serious side-effects such as impotence and incontinence, have so far dissuaded many European countries from nationwide screening.

A similar debate over breast cancer screening is also raging among doctors in Europe and United States, with critics of national mammography screening programs saying they needlessly harm thousands of women’s lives by picking up tumors that would otherwise not have caused a problem.

In a commentary on the Swedish study, David Neal from Britain’s Cambridge University, said it showed that “in certain circumstances, PSA testing and early diagnosis reduces death from prostate cancer.”

But he added: “It does not imply that PSA screening programs should now be introduced internationally.”

Source: Reuters

Popularity: 3% [?]

A way of fighting heart disease being pioneered by GlaxoSmithKline a boost today from a scientific study that appears in The Lancet stressed the significance of an artery-clogging enzyme. The study suggests that the enzyme, Lp-PLA2, plays as much of a role in the risk of heart disease as high blood pressure and bad cholesterol.

“Lp-PLA2 activity and mass each show continuous associations with risk of coronary heart disease, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population,” according to the study abstract. The researchers evaluated individual records from 79,036 participants in 32 prospective studies and did a meta-analysis of within-study regressions. Alex Thompson and John Danesh of Cambridge University, who conducted the research, said their findings would sharpen focus on an experimental drug called darapladib being developed by GSK and currently being studied in two large-scale clinical trials involving 27,000 patients worldwide, Reuters reports. Results of the trials are expected between 2012 and 2014.

“We’ve demonstrated that there is this positive association between Lp-PLA2 levels and vascular and nonvascular outcomes,” lead researcher Thompson told heartwire, “but what an observational study can’t do is establish causality. Given all the complexities about disentangling the effects of a measured level of an enzyme in the blood, given that it is carried around and is physically bound to apolipoprotein B on LDL, it is extremely difficult to do. To get that level of evidence, we are going to need randomized, clinical trials.”

“This BHF-funded research shows that Lp-PLA2, an enzyme that’s produced by inflammatory cells involved in the development of artery disease, appears to play a significant role in the progression of that disease,” Professor Peter Weissberg, medical director at the British Heart Foundation, says in a statement. “The acid test will then be to find out if such drugs reduce the risk of heart attacks and strokes in large clinical trials. It will be some time yet before we have the answers.”

GSK discovered darapladib through the use of gene technology from Human Genome Sciences. It is the first in a new class of drugs targeting Lp-PLA2 and is designed to offer something beyond the hugely successful class of cholesterol-lowering statin drugs like Pfizer’ Lipitor and AstraZeneca’s Crestor.

Source: FierceBiotech

Popularity: 3% [?]

The opportunity to save tens of thousands of HIV patients with a simple, cheap, drug treatment is being missed, say researchers.

Giving some newly-diagnosed patients an antibiotic would significantly reduce the death toll in the early stages of the disease, they say.

A major study in The Lancet medical journal found it halved mortality.

The World Health Organization already endorses the treatment, but specialists say many people are not given the drug.

Much of the focus of the pharmaceutical battle against HIV has been on antiretroviral drugs, which can greatly extend life.

However, many patients are at greatest risk in the first weeks after diagnosis, with a variety of infections ready to take advantage of their weakened immune systems.

Studies have estimated that as many as a quarter of people who enter antiretroviral drug treatment programmes in sub-Saharan Africa will die in the first year.

But the addition of co-trimoxazole, an inexpensive antibiotic, to the long-term treatment plan of those with the worst affected immune systems appears to prevent many of these deaths.

The Lancet study, carried out among 3,179 Ugandan patients, suggested a fall of 59% over the first 12 weeks, and 44% between 12 and 72 weeks.

Call for action

Its authors, from the Medical Research Council Clinical Trials Unit and Imperial College in London, and centres in Uganda and Zimbabwe, say the antibiotic is not available in many places.

They say their findings reinforce the need for swifter action by those responsible for drug treatment programmes.

Professor Charles Gilks, who led the study, said any arguments over the effectiveness of the antibiotics were now “well and truly answered”.

He said: “Tens of thousands of lives can be saved by more universal use of the drug, costing just a few pence a day.”

Co-author Professor Diana Gibb, from the Medical Research Council, said the availability and supply of the drug needed to be “ramped up”, and offered to all new patients for the first 18 months.

“There is a significant benefit now – waiting to be grasped,” she said.

In addition to preventing bacterial infections in HIV patients, the drug had a another welcome benefit – it cut the incidence of malaria by a quarter.

Dr Sarah Walker, also from the MRC, said: “The benefits of using this drug are huge, and it’s so simple and cost-effective to administer.”

However, Dr Alvaro Bermejo, the executive director of the International HIV/AIDS Alliance, said access to antiretroviral treatment remained an even bigger problem.

“We need to remember that there are still millions of people in Africa who need antiretrovirals and can’t access them.

“In Uganda the Alliance is seeing people turned away from clinics because they don’t have the treatment available.

“As the study confirms, antiretroviral treatment cuts the risk of death by more than 90% – with co-trimoxazole reducing the risk still further.

“We have the knowledge available to save lives but we need to increase efforts to make sure that everyone who needs treatment can actually access it.”

Source: BBC NEWS

Popularity: 2% [?]

A period of careful eating and regular exercise can stave off diabetes for a decade, a study suggests.

US researchers followed up nearly 3,000 overweight people who had taken part in a three year diabetes prevention programme.

The group had initially been divided into three – assigned either to a diet and exercise programme, the diabetes drug metformin or a placebo.

[ad]

The Lancet report notes it was the dieters who reaped the most benefit.

All three groups were given access to ongoing lifestyle coaching once the initial three year trial had ended.

That trial, carried out by the US-based Diabetes Prevention Program Research Group, had shown a diet aimed at achieving 7% weight loss, combined with half an hour of exercise five days a week, reduced the risk of developing Type 2 diabetes by 58% compared with the placebo group.

The group on metformin, a drug which has been used to treat the condition since the 1950s, saw their risk decline by nearly a third.

In the seven years after the trial ended, both the drug and placebo groups – now also eating more carefully and exercising – saw the rate of diabetes fall.

But the most significant drop was among those who had started out on a diet and exercise regime – their risk was over a third lower than the placebo group.

In an accompanying editorial, Dr Anoop Misra, a specialist in diabetes in New Delhi, described the prevention of the disease as “a long and winding road”.

‘No short cut’

Dr Misra said: “There seems to be no short cut, and a persistent and prolonged intensive lifestyle intervention seems to be the most effective way to travel on it.”

But he warned it could not be the only measure: “We need more effective drugs for those who cannot follow intensive lifestyle therapy because of infirmity.”

Type 2 diabetes usually appears in people over the age of 40, however increasing numbers of children are being diagnosed with the condition, some as young as seven.

Although obesity is a risk factor, not all people with type 2 diabetes are overweight.

Dr Iain Frame, head of research at Diabetes UK, said: “It is fascinating to read about the 10-year follow up studies and of the importance of lifestyle interventions, with or without metformin, in the prevention of Type 2 diabetes even after 10 years.

[ad]

“There is clearly no easy route to take to prevent Type 2 diabetes but indications are that with further research into the long-term benefits of good dietary advice, physical activity and, where necessary drug therapies, we may be a step closer into helping people at high risk of developing Type 2 diabetes modify their lifestyle choices that are sustainable in the longer term.”

Source: BBC NEWS

Popularity: 3% [?]

Physicians treating a woman with severe influenza A (H1N1) infection who was not responding to standard therapies stated that the patient’s condition improved after being treated with an unlicensed intravenous formulation of GlaxoSmithKline’s Relenza (zanamivir), according to a case study documented in The Lancet. The physicians wrote that “although this is a single case report and direct cause and effect cannot be confirmed, the improvement in clinical status following intravenous Relenza encourages prompt further investigation.”

[ad]

Prior to receiving intravenous Relenza, the condition of the patient, who had recently undergone chemotherapy for Hodgkin’s disease, had deteriorated to the point of requiring ventilation. The patient did not respond to treatment with Roche’s Tamiflu (oseltamivir) given orally twice daily, or the inhaled formulation of Relenza. However, after being administered the intravenous version of GlaxoSmithKline’s product in combination with high-dose corticosteroids, the patient’s condition improved within 48 hours and she recovered with no side effects, the doctors said.

Source: FirstWord

Popularity: 4% [?]

The combined use of proton pump inhibitors (PPIs) with sanofi-aventis and Bristol-Myers Squibb’s Plavix (clopidogrel), or with Eli Lilly and Daiichi Sankyo’s Effient (prasugrel), did not interfere with the clinical benefits of the antiplatelet agents in patients after an acute coronary syndrome (ACS), according to an analysis of study data to be published in The Lancet. Researchers noted that the results contrast with prior findings from other studies, and remarked that these latest data “do not support the need to avoid concomitant use of PPIs…in patients receiving clopidogrel or prasugrel.”

[ad]

The analysis was based on data from the randomised TRITON-TIMI 38 trial that enrolled over 13 600 patients who suffered a heart attack or unstable angina, and who were given either Plavix or Effient. The study authors evaluated the effects of PPIs in the trial, and they found that for patients who took these medications in combination with Plavix or Effient there was no increased risk of cardiovascular events, compared with patients who took Plavix or Effient alone.

A previous analysis of medical and pharmacy claims data by Medco indicated that among patients who had undergone a percutaneous coronary intervention, those who were being treated with Plavix plus a PPI had a 50-percent increase in the risk of having a major cardiovascular event, compared with those who took Plavix alone.

[ad]

The author of the Medco study, Robert Epstein, explained that the overall health of the patients involved in the studies may have played a role in producing contrasting results. He suggested that the new analysis involved healthier patients who were not in a “real-world setting.” The lead investigator of the latest study, Michelle O’Donoghue, noted that PPIs are often given to more seriously ill patients, which might explain why they experience more adverse events. However, she said such differences were adjusted for in the research. The authors stated that a thorough clinical trial is needed to clearly understand how PPI use affects treatment with antiplatelet drugs.

Source: FirstWord

Popularity: 5% [?]

Results of a study published in The Lancet suggest that pregnant women infected with the influenza A (H1N1) virus might be at increased risk for complications, including higher rates of hospitalisation and death. Scientists from the US Centers for Disease Control and Prevention, who conducted the study, called for physicians to “promptly treat pregnant women” infected with the virus using antivirals, such as Roche’s Tamiflu (oseltamivir) and GlaxoSmithKline’s Relenza (zanamivir).

[ad]

The study looked at the impact of influenza A (H1N1) on pregnant women from April 15, when the outbreak began, to June 16. Of 45 US deaths from influenza A (H1N1) during this period, six were in pregnant women, which represented 13 percent of deaths at the time. The CDC said of the 34 cases of influenza A (H1N1) in pregnant women reported to the agency from April 15 to May 18, 11 women were hospitalised, which was a fourfold increase in the rate of hospitalisation compared to the general population.

All of the pregnant women who died from influenza A (H1N1) complications were healthy prior to infection and subsequently developed viral pneumonia. The CDC said they did not receive antivirals soon enough to benefit from their treatment. Recommendations suggest that antiviral treatment be started within 48 hours after symptoms begin, however Denise Jamieson of the CDC, who led the study, said “some clinicians hesitate treating pregnant women with antiviral medications because of concerns for the developing foetus, but this is the wrong approach.”

Jamieson remarked: “We do not have evidence that pregnant women have increased susceptibility or are more likely to acquire influenza. It’s just that when they have influenza they are at increased risk of having severe disease.”

Source: FirstWord

Popularity: 5% [?]

Results of a study published Monday in The Lancet suggest the schizophrenia drug clozapine is associated with a “substantially lower” mortality in patients who take the product, compared with those who take other antipsychotics, researchers noted. Study leader Jari Tiihonen commented: “In all western countries, clozapine is recommended for use only as a second-line drug. I would like to see it considered for first-line use.”

[ad]

The study examined death rates in Finland between 1996 and 2006 in the general population versus those of about 67000 patients with schizophrenia who were taking the six most frequently prescribed antipsychotic drugs. Results showed that compared to patients treated with perphenazine, those who took clozapine had a 26-percent reduction in mortality, representing the lowest risk in the analysis. In addition, data showed that the highest increase in risk was observed in patients who took AstraZeneca’s Seroquel (quetiapine), who had a 41-percent increase in mortality compared with those who took perphenazine.

Patients taking clozapine, which is sold by Novartis as Clozaril and is also available as a generic, require regular blood tests for agranulocytosis. The researchers said that the difference in mortality seen in the study between clozapine and the other antipsychotic drugs may be attributable to more intensive monitoring during treatment with clozapine, greater effectiveness of clozapine, lower safety of other drugs, or all of these factors.

[ad]

Professor Tim Kendall, deputy director of the Royal College of Psychiatrist’s research unit, who was not involved in the study, stated: “These findings should be interpreted with real caution. The evidence for first-line use is not there. Clozapine is associated with a much broader range of side effects.”

Source: FirstWord

Popularity: 4% [?]

GlaxoSmithKline announced that type 2 diabetes drug Avandia showed no increased cardiovascular risk compared with commonly prescribed treatments, according to long-term study results presented at the annual meeting of the American Diabetes Association. The findings were also published in The Lancet and in an editorial accompanying the study, the authors stated that “definitive conclusions about the relation between [Avandia] and cardiovascular disease remain elusive, owing to study limitations.”

In the randomised RECORD trial, 2220 patients with type 2 diabetes were treated with Avandia as an add-on to metformin or sulphonylurea, and 2227 patients were treated with a combination of metformin and sulphonylurea. GlaxoSmithKline said the findings indicated that “cardiovascular hospitalisation and cardiovascular death (which includes heart attack, congestive heart failure, and stroke) was not statistically different between the two groups after an average of 5.5 years of therapy.” In addition, the company noted that glycaemic control was significantly better in the Avandia group after the average 5.5 years of treatment.

“The findings essentially are that, in overall cardiovascular terms, the drug is safe,” noted lead investigator Philip Home. “There’s no decreased risk, and that includes the heart failure element,” Home indicated, adding that “if anything, deaths were reduced with [Avandia] compared to those in the control group. It doesn’t reach statistical significance, but it’s on the right side of benefit.” Nonetheless, study researchers also stated that the data were “inconclusive about any possible effect on myocardial infarction,” and that results from the trial demonstrated that “the addition of rosiglitazone…is confirmed to increase the risk of heart failure.”

Bernard Zinman, co-author of the editorial appearing in The Lancet alongside the RECORD study, said that “it’s good there isn’t a strong negative signal but it doesn’t tell us it’s safe.” Zinman also indicated that the study “doesn’t tell us anything” about the drug’s propensity for causing heart attacks. Meanwhile, Cleveland Clinic cardiologist Steven Nissen described the trial as “seriously flawed.” He stated that not enough patients remained in the study to determine conclusively that the drug does not pose a higher risk for heart attacks and other cardiovascular problems.

GlaxoSmithKline spokesperson Mary Anne Rhyne commented that most patients who stopped taking Avandia did so near the trial’s end, which allowed researchers to make conclusions. The company released figures showing that 61 percent of patients in the Avandia arm and 51 percent patients in the control group remained on their medicines at the end of the study. Rhyne said that the numbers were not unusual for a trial where patients were followed for more than five years.

Nissen further remarked that the trial was made “worthless” by the fact that patients in the Avandia arm took 10 percent more cholesterol-lowering drugs. However, Home replied that the use of the lipid-lowering drugs could only have had a minor impact on the data.

In further reaction to the news, the chief scientific and medical officer of the American Diabetes Association, Richard Kahn, indicated that the association will evaluate the data and consider reversing its recommendation against using GlaxoSmithKline’s thiazolidinedione drug. The ADA’s recommendation came after the release of Nissen’s meta-analysis in 2007, which showed that Avandia increased the risk of heart attack by 43 percent and the risk of cardiovascular death by 64 percent, when compared with placebo or other treatment regimens.

Source: FirstWord

Popularity: 3% [?]