Synchrotron scientists suggest solution to sneezing sans sleepiness

As allergy sufferers we know all too well that although many over-the-counter antihistamines relieve symptoms, we’re are often too groggy to enjoy the respite. Now, thanks to some sleuth work by a team of international scientists, the way has been paved for antihistamines with fewer side-effects.

An international team of scientists has successfully cracked the  code for the complex 3-D structure of the human histamine H1 receptor protein. Using an X-ray beam 100 billion times stronger than normal,  at Diamond Light Source, the UK’s national synchrotron facility, researchers were able to get a 3D picture of the shape of H1 receptors.

Published this week in Nature, this discovery opens the door for the development of ‘third-generation’ antihistamines.

The H1 receptor protein is found in the cell membranes of various human tissues including airways, vascular and intestinal muscles, and the brain. It binds to histamine and has an important function in the immune system. However, in susceptible individuals it can cause allergic reactions such as hay fever, food allergies and pet allergies. Antihistamine drugs work because they prevent histamine attaching to H1 receptors.

Dr. Simone Weyand, postdoctoral scientist at Imperial College London, who conducted much of the experimental work at Diamond, said: “First-generation antihistamines are effective, but not very selective, and because of penetration across the blood-brain barrier, they can cause side-effects including sedation, dry mouth and arrhythmias.”

The team comprised of leading experts from The Scripps Research Institute in California, Kyoto University, Imperial College London and Diamond worked for 16 months on the project.

Professor So Iwata, Director of the Membrane Protein Laboratory at Diamond, said: “It took a considerable team effort but we were finally able to elucidate the molecular structure of the histamine H1 receptor protein and also see how it interacts with antihistamines. This detailed structural information is a great starting point for exploring exactly how histamine triggers allergic reactions and how drugs act to prevent this reaction.”

Word on Health’s allergy prone bloggers will be eagerly awaiting developments and will bring you news as it happens…assuming of course we can stay awake to do so!

Pharma Execs Indicted for Off-Label Promotion

While Word on Health has repeatedly written about the fines being levied against pharmaceutical companies, we were somewhat surprised to learn from the Philadelphia Inquirer of the indictments of four high-level medical device executives for off-label marketing practices.

Although, we’d heard threats that industry executives might have charges brought against them, many people thought these were nothing more than empty words.

These indictments therefore mark a bold step in the enforcement of off-label marketing practices in the US and will undoubtedly serve as a warning to others.

In these landmark cases, Federal prosecutors in Philadelphia indicted two company Presidents, a Vice President and a Director of Clinical Regulation at Synthes, a Pennsylvania-based orthopedic medical device company.

The company has already been fined $23.7 million for the off-label promotion of its Bone Cement but prosecutors are also seeking jail time for those they believe responsible and accountable for the illegal behavior. They point to at least three incident-related patient deaths resulting from off-label promotion and use of the product.

“We are concerned that the providers that engage in health care fraud may consider civil penalties the cost of doing business. As long as the profit from fraud outweighs those costs, abusive corporate behavior is likely to continue,” said Lewis Morris of the HHS Office of Inspector General (OIG) regarding the case.

While we all wonder if using pharma executives as a deterrent against “what not to do” will become the norm or whether this was simply a “one off”, it’s clear that there are now very real and very personal consequences to off-label promotion.

For people in the pharmaceutical industry maybe this news should serve as a “heads up” that it’s not enough to just talk about compliance, you really have to practice it at every level of the organization.

What’s your reaction to this development?  Let us know.

Mysterious Hep A Immune Response Has Implications For Hep C Research

Hepatitis C virus

SRxA’s Word on Health was interested to read a new animal study which sheds new light on the nature of the body’s immune response to hepatitis C virus (HCV) and hepatitis A virus (HAV).

By comparing these two viruses that infect the liver, one that is always cleared by the immune system – HAV, and one that frequently evades the immune response – HCV, the team hoped to unravel the mystery of how HCV causes lifelong persistent infections.

Understanding how the immune system responds to HCV is very important because more than 200 million people worldwide and 3.2 million people in the U.S. are chronically infected and at risk for progression to liver cirrhosis and liver cancer. Hepatitis C associated liver disease is the most common indication for liver transplantation, while liver cancer due to HCV infection is now the fastest growing cause of cancer death in the U.S.

“Hepatitis viruses have co-evolved with humans over a very long period of time and they are good at evading the immune system, but nobody understands how hepatitis C becomes a chronic infection,” commented study co-author Stanley M. Lemon, M.D., of UNC.

Hepatitis A virus

Surprisingly, the researchers found that HAV, a relatively benign virus that causes nausea, vomiting and lethargy, and has no chronic state was more adept at evading the innate immune response than HCV.  Examination of the adaptive immune system found that the T cell response to HAV was unique as well. Although the scientists expected the immune response to kill all HAV infected cells in a short time frame, instead they found that the genome of the virus could be detected in the liver for up to one year, long after symptoms of the disease were resolved.

The new study points out the critical need for more information about how the immune system reacts to HCV. It also reinforces the importance of animal research in this instance as the chimpanzee is the only animal model susceptible to HCV infection.

Such research is vital.

Unlike hepatitis A and B for which vaccines are widely available there is no hepatitis C vaccine. There are three basic reasons for this:

• As mentioned above, there is no effective small animal model or cell culture system. This makes vaccine development very challenging because researchers can’t see how the virus really works in a natural environment.
• HCV has different genotypes.  Since hepatitis C has at least six genotypes, several different vaccines would be needed to protect against each genotype.
• HCV mutates very easily. This means that some of its genetic code can change a little bit when it replicates itself. The result is a virus that keeps its genotype, but is different enough to confuse a vaccine.

Come to think of it,  HAV studies aren’t all that easy either. Almost 20 years ago I was peripherally involved with an HAV infectivity study. A biological product I was working with at the time had been implicated in the transmission of  HAV infection.  The suspect product was injected into chimps to see if they would develop the disease.  A second group of chimps housed in cages across the room were not injected, and served as controls. Unfortunately the study had to be terminated early because the test animals started throwing feces at the control group.

Not the outcome we were looking for, but a valuable exercise in the “how not’s” of clinical research!

Pharma Reps being replaced by iPads and Portals

As previously reported here, industry downsizing has resulted in the loss of over 30,000 sales positions over the past 5 years.   Now, according to a recent article in the Wall Street Journal, big pharma companies have found a way to replace many of the sales reps they’ve been laying off in recent years.  Apparently the void is being filled by digital sales tools such as websites and iPad apps. Doctors can use the tools to ask questions about drugs, order free samples and find out which insurers cover certain treatments. The changes are designed to cut costs and to reach doctors in ways other than the traditional office visit, which many busy physicians say they find intrusive and annoying. In 2009, one of every five doctors in the U.S. was what the industry calls a “no see,” meaning the doctor wouldn’t meet with reps. Just a year later that jumped to one in four.  Currently about three-quarters of industry visits to U.S. doctors’ offices fail to result in a face-to-face meeting. Throughout the 1990s and early 2000s, drug companies dramatically increased their U.S. sales forces, an escalation most companies came to regret as the economy took a downturn.  Many of those same companies are now involved in this digital shift including Sanofi-Aventis, Merck, Pfizer, GlaxoSmithKline, Novartis and Boehringer Ingelheim . Citing data from market-research firms, Eddie Williams, head of Novo Nordisk‘s biopharmaceutical business in the U.S., said 72% of U.S. doctors own a smartphone, and 95% of them use it to download medical applications. Novo Nordisk has several applications available on iTunes, including one that helps doctors calculate blood-sugar levels and another iPad/iPhone application which offers tools to help doctors diagnose bleeding disorders. Other companies such as Eli Lilly  are now considering “on-demand portals” that will allow doctors to access information instantly as they are treating patients. Although some companies have yet to be convinced of the benefits of e-marketing, most agree it is the way forward. Following the launch of Pradaxa in the U.S., Boehringer Ingelheim put together a digital-marketing package to target doctors, but found that sales calls to doctors’ offices were still the most powerful tool for driving new prescriptions, says. “No doubt digital marketing does have an impact…but I don’t believe, however, the shift happens overnight,” said Wa’el Hashad, the company’s VP of marketing. SRxA can help pharmaceutical clients with all of their digital marketing needs. Whether it’s interactive e-learning platforms, webinars, podcasts, e-newsletters, e-surveys or website design and development our fully customized, physician approved offerings will exceed your expectations. Contact us today to learn more.

A Bad Break for PPIs

A question for all our orthopedic, primary care, emergency medicine and physical therapy readers. When your patients come into see you with fractures do you ask them about their stomach?  No! – Well, maybe you should.  According to a recent meta-analysis, some of the drugs most commonly used to treat acid reflux can lead to fractures.

This is no small problem.  Millions of people worldwide are currently using these medicines often on a long-term basis. Each year sales of such drugs top $30 billion.

The type of medicines we’re talking about are more commonly known as Proton Pump Inhibitors (PPI) or Histamine-2 receptor antagonists (H2RAs). Among the former group are the best sellers such as Prilosec, Prevacid, and “the purple pill”- Nexium.  Among the latter: Tagamet (cimetidine) and Zantac (ranitidine). many are available over-the-counter.

The authors of the meta-analysis found that PPIs, which block acid production by up to 98%, are associated with an increased risk of both hip and any type of fracture. On the other hand, no significant relation was found between the H2RAs and fracture risk. Interestingly, H₂RAs block only 70% of gastric acid production.

It’s thought that bone fractures resulting from the use of PPIs are due to defective calcium absorption.  This can lead to hyperparathyroidism which in turn may modify acid-related enzymes in bones.

Given the widespread use of PPIs this study has great importance to public health. Clinicians should carefully consider their decision to prescribe PPIs for patients, especially the over-50’s who already have an elevated risk of fracture, and the orthopedic / emergency medicine community should routinely question their patients about the use of such drugs.

Pharma Pulls the Plug on Physician Travel

In what we believe is an industry first, AstraZeneca  just announced that it will no longer be paying for doctors to attend international medical conferences. Industry observers are already speculating that this move could put pressure on competitor companies to follow suit.

AstraZeneca’s Chief Executive Officer, David Brennan, announced the change of policy in low-key fashion at a recent industry conference earlier this month.

“We have decided that we will no longer pay for doctors to attend international scientific and medical congresses but will instead focus our educational efforts on local educational opportunities for healthcare professionals,” he said.

In recent years, concern has grown about financial ties between doctors and the pharmaceutical industry and ever tighter restrictions have been imposed.  Gone are the lavish entertainment and free drug lunches of the past, gone too are the pens, mugs and clocks.

Nevertheless, AstraZeneca’s decision to stop paying for doctors to fly to international medical and scientific meetings has taken things to a new level.

“It is a dramatic change,” Richard Bergstrom, Director General of the European Federation of Pharmaceutical Industries and Associations, said of the AstraZeneca move. “It is another sign that industry is changing its scientific education practices and I am sure you will see more moves of a similar nature by other companies,” Bergstom continued.

Brennan said he took the step because AstraZeneca should not do anything that could be seen as an inducement to prescribers to use its products. “We start from the position that our products stand on their own merits.”

Although the move will save money, the decision was not taken on cost grounds and any savings would have no significant impact on the company’s bottom line.

AstraZeneca’s move comes at a time of unprecedented regulatory pressure on the drug industry. In the past five years companies have paid more than $15 billion in penalties to the U.S. government alone for alleged violations of laws and regulations. This scrutiny has been ramped up with a wave of investigations under the U.S. Foreign Corrupt Practices Act (FCPA) and the introduction of a new bribery act in Britain.  Bribery legislation is an issue for pharmaceutical companies because doctors can be seen as government officials in those countries where they work for state-funded health systems. So, payments to them could trigger questions over corruption.

Just last month, Johnson & Johnson agreed to pay $78 million to settle British and U.S. charges it paid bribes and kickbacks to win business overseas, in the first settlement by a big drug company since the U.S. began scrutinizing the industry under the FCPA more than a year ago.

Last year AstraZeneca agreed to pay $520 million to settle claims over illegal marketing of Seroquel and is currently being investigated by the U.S. Department of Justice and the Securities and Exchange Commission in connection with the FCPA.

While SRxA’s Word on Health applauds this latest move from AstraZeneca, we can’t help wonder what it means for the medical conference industry.  If doctors have to pay for their own travel and attendance at international events will they simply stop going?

Let us know what you think.

Asthma drug helps shed pounds

According to new research, a drug commonly used to treat asthma and COPD may also burn fat.

When taken in pill form, the drug formoterol boosted fat burning while preserving protein metabolism, and muscle mass.

“Fat burning was increased up to 25%,” says researcher Paul Lee, MD, PhD, of the Garvan Institute of Medical Research and an endocrinologist at St. Vincent’s Hospital in Sydney, Australia.

Formoterol is used as an inhaled medication for asthma and chronic obstructive pulmonary disease (COPD) and is one of the ingredients in Symbicort and Dulera.

In this study, Lee used it in pill form, and gave it to 8 men at a dose of 160 micrograms a day for one week. Before and after the study, he measured the men’s energy rates, fat oxidation, and whole body protein metabolism.  Each time, the measurements were taken after the men drank a standardized, high-carbohydrate liquid meal.

Comparing their before and after rate, their overall energy rate increased by more than 10% and their fat burning by 25%.

Theoretically, an average person weighing 155 pounds could burn an extra 200 calories a day with the pill. Over time, that could translate to noticeable fat loss and maintained or gained muscle.

The inhaled form of the drug can cause tachycardia – an abnormally fast heartbeat, but Lee did not see this side effect in the patients who took the pill form. “Some had insomnia, but it was mild,” he says. It was also temporary. “Some reported loss of appetite.”

In addition to burning fat, the drug might prevent or treat muscle wasting that can accompany age. “It may potentially reverse or prevent this process and treat frailty,” Lee says.

”The report is certainly intriguing,” says Bruce Wolfe, MD, President of the American Society for Metabolic and Bariatric Surgery and Professor of Surgery at Oregon Health and Science University, Portland.  However, he cautions that the increase in fat burning is modest. Eating a couple of cookies, or drinking a small glass of wine could undo the benefit. Nevertheless, over time, taking the formoterol could make a noticeable difference.

SRxA’s Word on Health eagerly awaits the results of further studies.

What Are Your Telomeres Telling You?

When it comes to the science of aging, there are few discoveries as intriguing as telomeres.  These caps at the ends of chromosomes protect genes from being eroded each time a cell divides. When telomeres are finally eaten away after many years, cells begin to show signs of aging. This process is thought to be a key part of what makes us grow old.

 Telomeres’ partner in crime is the enzyme telomerase, which helps keep telomeres long and healthy, a property that’s made it the subject of almost science-fictional fascination.  Telomerase confers immortality on cancer cells and has even been shown to reverse aging in telomerase –deficient rats.

Now, in a move that brings these questions into sharper focus for the general public, Telome Health, founded by Elizabeth Blackburn, who won the 2009 Nobel Prize for Medicine for her work in this area, has announced that it will bring to market a test for telomere length.

The company already provides such a test for research use, but according to its website it will release a test for the general public this fall

News of the test’s release has spurred a flurry of misleading reports suggesting that we’re on the cusp of being able to learn how long we’ll live — and whether we can ward off the irksome outward signs of aging.

While scientists are divided over the value of the test for individuals, no serious researchers are saying a telomere test will be some kind of crystal ball. However, if people can monitor their telomere length, perhaps they can make lifestyle changes to alter that risk by boosting their cells’ longevity.

SRxA’s Word on Health is asking its readers: Would you take the test?  Let us know.

Patients Don’t Pooh-Pooh Fecal Transplants

Let’s start this blog with the disclaimer that what you’re about to read has a high “yuck” factor…unless it seems you’re a patient or a parent of a patient with ulcerative colitis.

A new study just published in the journal Inflammatory Bowel Disease examined the social and ethical issues associated “fecal microbiota transplantation” (FMT).

Yes, FMT is just what you’re thinking it is!  Also known as fecal bacteriotherapy, it is a provocative treatment performed in an attempt to calm a troubled bowel by reintroducing the vast diversity of collaborative bowel inhabitants after the usual mix has been disturbed. More than 1,000 different strains of bacteria co-exist peacefully in the typical healthy bowel. But when the delicate balance is altered, by antibiotics or other causes, a few strains can become dominant, leading to severe diarrhea, inflammation and tissue damage.

Although transplants of fecal matter have been used sporadically to treat gastrointestinal disease for more than 50 years, more recently, the approach has produced lasting remissions for a small number of patients with ulcerative colitis.

The first fecal transplants date back to 1958, when they were used to treat life-threatening bowel infections. They did this by collecting fecal matter from a healthy donor and injecting it into the patient’s colon.

Then in 2003, an Australian team published a report on successful treatment of six patients with longstanding ulcerative colitis with this approach.

And although you may be feeling a little squeamish by now, it seems that patients with severe inflammatory bowel disease develop a high tolerance for therapies that others might consider unorthodox. According to study author David Rubin, MD, Associate Professor of Medicine at the University of Chicago, “Once patients get past the yuck factor they find the concept appealing.”

Like an organ transplant, fecal microbiota transplantation begins with finding a donor, often a family member. The treatment team collects a fresh stool sample of at least 200 – 300 grams (7-10 ounces). The sample is mixed with salt water in a blender and filtered to remove particulate matter. It can be administered to the recipient through a colonoscope, as an enema, or, when the inflamed region is higher in the colon, through a nasogastric tube.

The researchers organized six focus groups with patients or parents of children with ulcerative colitis to explore the attitudes and concerns raised by this approach.

They found that:

• 21:22 patients or parents of patients were interested in trying FMT for themselves or their child
• Most wished it were already available
• They viewed the treatment as more ‘natural’ than using drugs to control the disease, and easier and safer than currently available therapies
• Many compared it to probiotics, a popular alternative therapy among patients with colitis.

The major concerns were focused on how donors would be selected and screened. Patients wanted healthy donors, usually family members, and asked that even their diet and medications be considered. A donor who had eaten peanuts recently, for example could be hazardous for a recipient with peanut allergies.

The “yuck” factor came up in the focus group discussions of bacterial delivery. Patients and parent were comfortable with the idea of a “spray” colonoscopy or delivery via enemas, but were disturbed by the idea of using a nasogastric tube for the transfer of fecal bacteria.

“What our study ultimately tells us is that patients are not only tolerant of this therapy but are eager for it to become available,” Rubin said. “A few have already tried this strategy at home, using ‘protocols’ they found on the internet and tools available at any drug store.”

The team plans to begin offering FMT this fall.

Would you sign up for a poop transplant or consider being a donor?

Pharma Philanthropy

All too often the pharmaceutical industry is portrayed as evil and greedy. In an attempt to correct this misconception or at least redress the balance a little, SRxA’s Word on Health is pleased to bring you news of its more compassionate side.

According to figures just released by the Committee Encouraging Corporate Philanthropy poll, drug companies gave away more than $13 billion in cash and products last year.

More than half of the $2 billion increase in corporate philanthropy last year came from pharmaceutical companies donating medicine through their Patient Assistance Programs and investing in other initiatives.

While 40% of the 110 companies – polled annually for the past four years – boosted their giving last year by more than 10%, another 17% decreased their giving compared to 2009.

“One of the reasons we have seen for increased giving across the board has been increased funding to serve basic needs in communities where companies are working, and pharmaceutical companies, in particular, are in a really important position to do so,” said Alison Rose, the committee’s manager of standards and measurement.

Companies in the consumer staples, financial, industrials and information technology sectors also contributed to the increase in 2010 corporate philanthropy.

So where is all this pharma money going?  According to the websites of the Top 5 global pharmaceutical companies examples of corporate giving included:

• Johnson & Johnson contributed $588.1 million in cash and products towards 650 philanthropic programs in more than 50 countries

• Pfizer contributed to numerous charitable projects worldwide including > $47 million for cancer and tobacco control and $7.5 million to HIV / AIDS prevention

• Roche notes that as a result of some of their 2010 initiatives 47,000 patients received free medicines, 1,100,000 infants were tested for HIV, 11,000,000 doses of flu vaccine were donated and 2,000 orphaned children  were given primary healthcare and other services and assistance through support to the UNICEF & ECPP

• GSK among their many programs around the world, donated more than 1.6 billion tablets of a drug used to combat intestinal worms.  In the US, GSK supported numerous cancer charities and  provided health education in non-traditional venues for African Americans, Latinos and other ethnic minority communities and set up programs across six states to help high-risk and homeless children receive the specialist medical care they need.

• Novartis supports many programs both in the US and internationally. In the US alone, their patient assistance programs provided products worth $232 million to more than 100,000 patients in need. Additionally, they have provided free treatment for leprosy patients worldwide, leading to the cure of about 5 million patients since 2000 and has delivered more than 320 million treatments of its antimalarial drug without profit to several malaria-endemic countries

These are but a few examples of the type of corporate responsibility being shown by the pharmaceutical companies day-after-day.  Ladies and gentleman of the Industry we applaud you.