U.S. warns about bed-wetting drug after 2 deaths

From Reuters.com:

WASHINGTON (Reuters) - U.S. health officials alerted the public on Tuesday about the deaths of two patients who were treated with a prescription drug to control bed-wetting.

The Food and Drug Administration said it was unclear whether the drug, desmopressin, had contributed to the deaths. But the agency said nasal versions were no longer approved for treating bed-wetting and doctors should consider other options.

Desmopressin is sold under the names DDAVP Nasal Spray, DDAVP Rhinal Tube, DDVP, Minirin and Stimate Nasal Spray. Makers include Sanofi-Aventis and several generic companies.

Other forms of the drug "should be used cautiously" in patients at risk of sodium imbalances that can be caused by over-hydration, the FDA said.

The agency reviewed 61 reports of patients treated with desmopressin who developed seizures related to hyponatremia, when sodium is too low. Two of the patients died.

"The direct contribution of desmopressin to the deaths is unclear," the FDA said in a notice posted at www.fda.gov/cder/drug/InfoSheets/HCP/desmopressinHCP.htm. The patients who died were ages 28 and 80, FDA spokeswoman Susan Cruzan said.

Thirty-six seizure reports were associated with intranasal forms of the drug, the FDA said. Those versions should not be used in patients with hyponatremia or a history of the condition, the FDA said.

The agency also said treatment with desmopressin tablets should be stopped during episodes that may trigger extra fluid intake, including fever, recurrent vomiting, diarrhea and vigorous exercise.

BREAST CANCER DRUG GRANTED ADDITIONAL SIX MONTHS OF PATENT PROTECTION

From Drugtopics.com

Anastrozole (Arimidex, AstraZeneca) has been granted an additional six months of patent protection by the FDA under the agency's pediatric exclusivity rule. The change came after the manufacturer performed clinical trials examining the use of anastrozole in children. Interestingly, the patent extension was still granted despite the fact that no therapeutic potential was found for anastrozole in the pediatric population and AstraZeneca will not seek an approval for an indication in children. Currently, anastrozole is approved for use in adults as first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer, for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer, and for treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.

Addex and Merck & Co., Inc. Collaborate to Develop Drugs for Parkinson's Disease

GENEVA, Switzerland, Dec. 3, 2007 - Allosteric modulation company Addex Pharmaceuticals (SWX:ADXN) announced today that it has entered an exclusive collaboration and license agreement with Merck & Co., Inc. (through its affiliate Merck Sharp & Dohme Research Ltd) with the goal of developing a new class of orally available drugs, initially as candidates for the treatment of Parkinson's disease and potentially other undisclosed indications. The partners will discover and develop positive allosteric modulators (PAMs) targeting the metabotropic glutamate receptor 4 (mGluR4). The deal includes lead mGluR4 PAMs discovered by Addex.

"We are proud to have established this collaboration with Merck because their researchers have helped to define the therapeutic potential of targeting mGluR4 to treat Parkinson's disease," Vincent Mutel, CEO of Addex, said. "This is another important validation of our leadership in allosteric modulation."

"Addex has made exceptional progress in the area of mGlu receptor allosteric modulation," said Darryle D. Schoepp, Ph.D., senior vice president and franchise head, Neuroscience, at Merck Research Laboratories. "This partnership is key to us jointly establishing a leadership position in the promising area of mGluR4 receptor modulation for Parkinson's disease. Merck scientists are excited to work with Addex to extrapolate the full value of this novel mechanism for a range of neuroscience disorders."

Parkinson's disease is a debilitating movement disorder. Current treatments focus on dopamine-replacement strategies, however most patients reach a stage where these treatments are no longer effective. There can also be debilitating side effects with current treatments and many patients limit doses so their symptoms are less cumbersome. The recent success of surgical approaches suggests that bypassing the dopamine system may provide a more effective treatment strategy. It is believed that selective activation of mGluR4 is one way to do this and could correct the circuitry that modulates motor excitability. This has the potential to provide significant palliative benefit in Parkinson's disease.

Under the terms of the agreement, Addex will receive $3 million upfront and is eligible for up to $106.5 million in research, development and regulatory milestones for the first product developed for multiple indications. Additional milestones of up to $61 million would be payable if a second and third product is developed. Addex is eligible to receive undisclosed royalties on sales of any products resulting from this collaboration.

Addex and Merck will collaborate on preclinical development. Merck will be responsible for clinical development. Addex has an option to co-promote in certain European Union countries and will participate in the joint oversight committee for clinical development. Addex will host a webcast & teleconference (see below).

Targeting glutamate receptors

Like dopamine and serotonin, glutamate is a key neurotransmitter in the human brain, an important signaling molecule involved in control of multiple brain functions ranging from motor control to mood. Although marketed drugs modulate specific receptors involved in both the dopaminergic and serotinergic systems, it has been difficult to develop drugs that target specific G protein coupled receptors in the glutamatergic system.

Merck has been a pioneer in research on mGlu receptors and the metabotropic glutamatergic system for multiple indications. For example, research by Merck scientists provided the first evidence that mGluR4 activation has potential for treatment of Parkinson's disease. However, a remaining challenge has been to make drug-like molecules that activate mGluR4 in a specific fashion. Addex is a pioneer in developing truly selective small molecule drug candidates targeting glutamate receptors and has previously disclosed programs targeting mGluR5 and mGluR2. mGluR4 in Parkinson's disease

Published research* shows that mGluR4 activators, like those in development at Addex, could work via two distinct mechanisms to alleviate symptoms of Parkinson's disease and, potentially, even slow the progression of the disease: 1) mGluR4 activation triggers a compensatory mechanism that may spare or potentiate the use of dopamine receptor activators; 2) mGluR4 activation may have a neuroprotective effect that helps to preserve the brain's dopaminergic neurons.

*Nature Reviews Neuroscience, Vol 6, Oct. 2005, pp 787-798

About Parkinson's disease

Parkinson's disease is a brain disorder. It occurs when certain nerve cells (neurons) in a part of the brain called the substantia nigra die or become impaired. Normally, these cells produce a signaling molecule (neurotransmitter) known as dopamine. Among other things, dopamine allows smooth, coordinated function of the body's muscles and movement. When approximately 80 percent of the dopamine-producing cells are damaged, the symptoms of Parkinson's disease appear.

Parkinson's disease affects both men and women in almost equal numbers. It shows no social, ethnic, economic or geographic boundaries. In the United States, it is estimated that 60,000 new cases are diagnosed each year, joining the 1.5 million Americans who currently have Parkinson's disease. While the condition usually develops after the age of 65, 15 percent of those diagnosed are under 50.

Most symptoms associated with Parkinson's disease, like tremor, rigidity and slowness, are caused by a lack of dopamine. Marketed medicines help to ease the symptoms of Parkinson's disease by either replacing or mimicking dopamine. Currently, no marketed products slow the disease progression. No marketed products work via non-dopaminergic mechanisms.

About Addex

Addex Pharmaceuticals discovers and develops allosteric modulators, an emerging class of small molecule therapeutic agents. Allosteric modulation may offer more sophisticated ways to normalize biological signaling compared to classical orthosteric agonist or antagonist drugs. Allosteric, literally translated from its Greek roots, means: other site. Thus, allosteric modulators bind receptors at sites that are distinct from the binding sites of classical small molecule "orthosteric" agonist and antagonist drugs.

The most advanced drug candidate, ADX10059, a negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5), recently demonstrated clinically and statistically significant efficacy in separate Phase IIa clinical trials in gastroesophageal reflux disease (GERD) patients and migraine headache patients. Data from another Phase IIa clinical trial of ADX10059 in acute anxiety are due around the end of 2007.

The Addex discovery capability has previously been validated through a collaboration with Ortho-McNeil, a Johnson & Johnson company. The deal is limited to discovery and development of allosteric modulators of metabotropic glutamate receptor 2 (mGluR2).

In May 2007, Addex completed an initial public offering on the SWX Swiss Exchange, raising CHF137 million ($111 million /€83 million). The IPO was the largest biotech IPO in Europe in three years.

FDA Approves Diovan for Treatment of High Blood Pressure in Children

From Drugs.com:

EAST HANOVER, N.J., December 03, 2007 /PRNewswire/ -- Diovan (valsartan), an angiotensin receptor blocker or ARB, has been approved following a priority review by the U.S. Food and Drug Administration (FDA) for the treatment of high blood pressure in children and adolescents ages six to 16.

High blood pressure has become a multigenerational health issue. Thirty percent of American adults are currently living with high blood pressure and now there are reports that nearly five percent of children and adolescents may have this condition(1).

Experts suggest that the increase in incidence of high blood pressure among children and adolescents is linked to the growing pediatric obesity epidemic(2,3). Based on the National Health and Nutrition Surveys (NHANES), the percentage of overweight children (six to 11 years old) increased from 13.8% to 16.0% between 1999 and 2004, while the share of overweight adolescents (12 to 19 years old) rose from 14.0% to 18.2% during the same period(4).

"Novartis believes it is important to provide physicians with treatment options such as Diovan which are effective in treating high blood pressure in this vulnerable population of children and adolescents," said John Orloff, MD, Senior Vice President, Medical and Drug Regulatory Affairs, Novartis Pharmaceuticals Corporation.

No relevant differences were identified between the adverse experience profile for pediatric patients aged six to 16 and that previously reported for adult patients. Diovan is not indicated for treatment in children under six years old.

About Diovan

Clinical studies have shown that Diovan effectively lowers blood pressure. Diovan specifically blocks a hormone that causes arteries to constrict (tighten and narrow), an action that can cause high blood pressure.

In adults, Diovan is indicated for the treatment of hypertension when used alone or in combination with other high blood pressure agents. Diovan is also indicated for the treatment of heart failure (NYHA class II-IV). In clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction, Diovan is indicated to reduce cardiovascular mortality.

Taking Diovan during pregnancy can cause injury and even death to an unborn baby. If you get pregnant, stop taking Diovan and call your doctor right away. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant.

Do not take Diovan if you are allergic to any of the ingredients in this product.

Diovan is not recommended for treatment in children with glomerular filtration rate <30 mL/min/1.73 m(2).

The most serious side effects with Diovan are low blood pressure (hypotension) and kidney problems. Other side effects with Diovan have generally been mild. In hypertensive patients, the most common side effects with Diovan are headache and dizziness.

The most common side effects of Diovan when used to treat people after a heart attack which cause them to stop taking the drug include low blood pressure, cough, rash and high blood creatinine (decreased kidney function). When used to treat people with heart failure, the most common side effects include dizziness, low blood pressure and diarrhea.

Diovan is a prescription medication.

Do Medical Schools Affect the Way Future Doctors Interact with Drug Companies?

From Drugs.com:

INDIANAPOLIS, Dec. 3, 2007 – Although more and more drug advertisements are appearing on television, the bulk of the approximately $21 billion dollars that pharmaceutical companies spend annually to market their products is targeted to physicians, doctors in training (residents) and medical students.

A literature review by researchers from the Indiana University School of Medicine and the Regenstrief Institute, Inc. published in the December issue of the journal Pediatrics focuses on the interaction between drug companies, medical students and residents and concludes that well-designed seminars, role playing and focused curricula can affect medical student and resident attitudes and behavior toward drug companies.

The review, led by Aaron E. Carroll, M.D., M.S., assistant professor of pediatrics with the Children’s Health Services Research at the IU School of Medicine and a Regenstrief Institute affiliated scientist, scrutinized the recent literature in the field. Dr. Carroll and colleagues found 12 studies since 1991 focusing on the efforts of academic medical centers to modify the relationship between pharmaceutical companies and medical students and residents.

“Not surprisingly, we found that the greatest impact medical schools had on the interaction of medical students and residents with drug companies was if the school banned all contact with company representatives. But even requiring medical students or residents to participate in one hour of training had an impact on the relationship,” said Dr. Carroll, who is also with Riley Hospital for Children, a Clarian Health Partner.

The study authors reported evidence that policy decisions to restrict contact between trainees and the pharmaceutical industry were associated with greater skepticism toward information given by drug company product representatives and altered behavior in future contact with drug company representatives.

“Doing nothing is no longer an acceptable option. Medical schools need to bring up the complex financial, medical and ethical issues involved in the interactions between doctors and drug companies. Fortunately doing almost anything seems to have at least a minimal impact,” said Dr. Carroll.

SMOKERS COST MEDICAID NEARLY $10 BILLION

From newswise.com:

Five years after all current smokers who receive Medicaid benefits quit smoking, program expenditures would be an estimated $9.7 billion lower, according to a new report by researchers at RTI International.

The report, funded by the American Legacy Foundation, found that Medicaid expenditures attributable to current smokers account for 5.6 percent of total national Medicaid expenditures.

"Reducing the number of smokers in the United States could save taxpayers billions of dollars in Medicaid costs," said Justin Trogdon, Ph.D., an RTI health economist. "Policy makers looking for ways to reduce health care costs in America would be wise to look at areas of health behaviors that both improve health and reduce health care costs."

According to the research, New York smokers top the list, costing Medicaid $1.5 billion each year. Wyoming had the least Medicaid expenditures due to current smokers, but they still cost the program $15 million each year. The report showed that North Carolinians who smoke cost Medicaid $294 million each year.

The researchers also looked at the cost of Medicaid over the lifetime of 24-year-old smokers because nearly all smokers begin smoking before age 24.

"The benefits of preventing smoking initiation accrue over a longer time horizon," Trogdon said. "Life-cycle estimates are important in gauging the long-term impact of youth smoking prevention on state Medicaid programs. These estimates take into account the differences in life expectancy for smokers and nonsmokers as well as payments into the Medicaid system by smokers."

"This study underscores the need for strong and effective smoking prevention and cessation campaigns," said Cheryl G. Healton, Dr. PH, president and CEO of the American Legacy Foundation. "We hope that this report will serve as a tool for states to use when setting both long- and short-term goals for reducing Medicaid expenditures associated with tobacco use."

The results showed that, over the course of their lifetime, today's 24-year-old smokers will cost Medicaid almost $1 billion. However, most of those costs are due to female smokers, not males.

The researchers found that over the course of their lifetime, tax payments by young male smokers make up for most of their extra Medicaid expenditures from smoking, but the expenditures for female smokers cost Medicaid about $1,300 per person.

This impact is highest in Texas, where the lifetime costs of 24-year old smokers to Medicaid is estimated to be $125 million. In North Carolina, those costs are expected to reach almost $37 million.

"The lifetime costs of young smokers are for one cohort of 24-year-olds," Trogdon said. "Every year a new group of young people will turn 24. Based on these findings, preventing and reducing youth smoking, especially among females, could lower Medicaid costs by billions of dollars."

The research is based on data from the 2000 through 2004 Medical Expenditure Panel Surveys.