Beating the Mets?

As fans of the New York Mets know all too well, in recent years they’ve been all too easy to beat.  However, another type of mets have remained somewhat harder to beat.

Metastatic cancer, more commonly referred to as “mets” is cancer that has spread from the place where it first started to another place in the body. The process by which cancer cells spread to other parts of the body is called metastasis.

Although some types of metastatic cancer can be cured, most cannot. In general, the best that can be done is to control the growth of the cancer or to relieve symptoms caused by it. In some cases, metastatic cancer treatments may help prolong life, but sadly, most people die of metastatic disease.

Now it seems there may be a way to beat the mets off the baseball field as well as on it.

Researchers are harnessing viruses to infect and subsequently destroy cancer cells without affecting normal tissue. Several types of viruses have been developed to date: adenovirus, poxvirus and picornavirus.  Even the herpes simplex virus is under consideration.

As are reoviruses, which are currently being studied by the National Institutes of Health (NIH).  Early results indicate that reoviruses could be especially effective in treating metastatic cancers.

Reoviruses are found everywhere in nature. They have been isolated from untreated sewage, river and stagnant waters. These viruses choose to colonize certain types of mutated cancer cells while sparing normal cells that lack these mutations. Approximately two-thirds of human cancers have the mutation that makes them a prime target for reoviruses.

One of the new drugs based on reovirus is known as REOLYSIN^®, an acronym for Respiratory Enteric Orphan Virus, which is widely found in the environment. By adulthood, most people have been exposed to this reovirus. As it is non-pathogenic, infections are typically asymptomatic.

REOLYSIN^®  was developed, based upon research conducted by Dr. Matt Coffey.  He found that the reovirus was able to infect and selectively destroy cancer cells. When a normal cell is infected with the reovirus, an antiviral response is activated, which prevents the virus from replicating within the cell. However, inside a cancer cell with one or more mutations on a growth pathway called the Ras pathway, there is an aberrant antiviral response that is unable to prevent the virus from replicating. This abnormality allows the reovirus to multiply to an extent that is fatal to the cancer cell.

Additionally, reovirus appears to spread particularly easily to organs where metastasis is common, so a concentration of the drug can be built up in those regions of the body.

REOLYSIN is currently being studied in combination with the chemotherapy drugs in six of the ten most common cancers diagnosed in men and five of the ten most diagnosed in women, including patients with head and neck cancer, non-small cell lung cancer, colorectal cancer, castration-resistant prostate cancer, drug-resistant ovarian cancer and pancreatic cancer. All of these indications are associated with metastatic disease.

The American Cancer Society estimates there will be more than 1.6 million new cancer cases diagnosed in the United States alone in 2012; more than 1,500 people a day are expected to die from the disease.

So, could a sewage water virus be the answer? SRxA’s Word on Health will be watching out for the results of these studies and let our readers know if they’ve truly found a way to  “beat the mets.”

It’s here! HIV Prevention in a Pill

An estimated 1.2 million Americans are currently living with HIV. Despite the availability of condoms and HIV education, the incidence rate has remained steady over the past two decades with approximately 50,000 new infections occurring each year. 23% of these new cases occur among women and 61% occur among men who have sex with men.

In the 80′s and early 90′s, HIV was viewed as a life-threatening disease. In some parts of the world, it still is. And while medical advances, along with the availability of 30 or so approved HIV drugs, mean its now a chronic disease, rather than a killer disease – what we’ve all been waiting for is a drug to prevent it.

Now, this week, after decades of anticipation, the FDA  approved Truvada – an HIV combination pill for pre-exposure prophylaxis.  Truvada is the first drug that has been approved to combat HIV among uninfected individuals who are believed to be at high risk of acquiring the virus. Analysts estimate that the drug will cost $450 a year in the U.S.

In a study sponsored by the National Institutes of Health, Truvada was shown to significantly reduce the risk of HIV infection in 42% of HIV-negative gay and bisexual men and transgender women. In another, the risk was lowered in 75% of heterosexual couples in which one partner was HIV positive and the other was not.

“The data clearly demonstrate that Truvada, as pre-exposure prophylaxis, is effective at reducing the risk of HIV infection acquired through sexual exposure,” said Connie Celum, a professor of global health and medicine at the University of Washington and lead investigator of the second study.

As part of the approval, the FDA has stipulated that patients must test negative for HIV and that education guides must be distributed to healthcare providers and patients. And the manufacturer – Gilead must conduct a post-approval trial looking at levels of drug adherence, adverse events, resistance and pregnancy outcomes for women who become pregnant while taking Truvada.

The approval of Truvada comes after a long-running debate among AIDS activists. To some, FDA approval offers much-needed assistance in containing the disease. To others, it raises the possibility of creating resistant strains of HIV due to widespread use, just as we saw in the 1960’s with antibiotics, which would then undermine the effectiveness of Truvada.

While the approval may be a cause of celebration for many, some have blasted the decision. “The FDA’s approval of Gilead’s Truvada as a form of HIV prevention today without any requirement for HIV testing is completely reckless and a move that will ultimately set back years of HIV prevention efforts,” says AIDS Health Foundation president Michael Weinstein. “The FDA’s move today is negligence bordering on the equivalence of malpractice, which will sadly result in new infections, drug resistance and serious side effects among many, many people.”

So is this a watershed moment in the battle against HIV or not?  Let us know what you think.

You Can Teach an Old Drug New Tricks

Drug discovery is a laborious process.

From initial discovery of a promising target to the final medication becoming available, is an expensive, and lengthy process. At present, the costs of bringing a single new drug to market is around $1.2 billion, an amount that doubles every five years.

Aside from the cost, it takes, on average, 12 years for an experimental drug to progress from bench through FDA approval to market.

Annually, North American and European pharmaceutical industries invest more than $40 billion to identify and develop new drugs. Even so, for every 5,000 compounds that enter pre-clinical testing, only five, on average, are tested in human trials, and only one of these five receives approval for therapeutic use.

So, it’s hardly surprising that many pharmaceutical companies are choosing to take a closer look at old drugs. Last week, SRxA’s Word on Health brought you news of a host of potential new uses for aspirin.

And aspirin is not alone.  Old drugs often get a surprising second shot at life. In the past few weeks, the news has buzzed about the skin cancer drug – bexarotene – that may cure Alzheimer’s; a common antimalarial drug – hydroxychloroquine – that may help to destroy cancer; and, a leukemia drug that inhibits the Ebola virus.

Then, of course, there’s the personal favorite of many women – Latisse.  Originally developed as a glaucoma treatment , it was found to have the desirable side effect of making eyelashes fuller and longer and is now FDA approved for this purpose.

Testing drugs already approved for one use to see if they can treat other conditions, can reduce time and money. Since these known drugs have already undergone toxicology and safety testing, the clinical development program can be streamlined.

Sometimes it’s pure serendipity.

Take Viagra for example. Although these days it’s the stuff of pharmaceutical industry legend , in the early 1990s, it was just a chest pain drug that wasn’t performing very well in clinical trials. So how did the little blue pill go from heart to crotch?  Pfizer was ready to call it quits when they decided to look into one unexpected but common side effect: long-lasting erections. Then came the drug patent and the rest is history.

The discovery that lithium could be used to treat manic episodes in bipolar patients was equally fortuitous. In 1949, Australian psychiatrist John Cade was injecting guinea pigs with urine extracts from schizophrenia patients to try and isolate a compound that caused mental illness. By accident he happened to use a compound with lithium – which at the time was used as a treatment for gout, as the control. Although he didn’t find the compound that caused mental illness, he did find one that treated it!

Back in 2010 we reported on the repurposing of thalidomide. Although the drug caused serious birth defects when it was launched in the 1960’s as a morning sickness pill it has since been found to be useful in reducing severe and frequent bleeding in patients with  hemorrhagic telangiectasia (HHT); in the treatment of patients with newly diagnosed multiple myeloma when taken  in combination with dexamethasone; and for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum

The National Institutes of Health (NIH) recently established The Learning Collaborative (TLC) to study how to more easily repurpose known drugs to treat rare forms of blood cancers.

TLC is a dedicated collaboration between the NIH Chemical Genomics Center (NCGC) and its Therapeutics for Rare and Neglected Diseases (TRND) program, The Leukemia & Lymphoma Society (LLS), and Kansas University Cancer Center (KUCC) to discover and develop new drug therapies for rare blood cancers. TLC is creating a pipeline of new therapies to treat leukemia from both the discovery of new treatments as well as identifying new uses for approved and abandoned drugs.  For example, Auranofin, a drug originally used for rheumatoid arthritis, is now in clinical trials for treating chronic lymphocytic leukemia.

Word on Health will continue to follow the drug recycling trend and bring you news as it breaks. In the meantime if you have noticed any beneficial side effects from the medicines you’re taking, we’d love to know.

Sweet Protection Against Parkinson’s Disease

New research shows men and women who regularly eat berries may have a lower risk of developing Parkinson’s disease.  Men may further lower their risk by regularly eating apples, oranges and other sources rich in dietary flavonoids.

The study which was supported by the National Institutes of Health involved 49,281 men and 80,336 women. Researchers gave participants questionnaires and used a database to calculate intake amount of flavonoids. They then analyzed the association between flavonoid intakes and risk of developing Parkinson’s disease. They also analyzed consumption of five major sources of foods rich in flavonoids: tea, berries, apples, red wine and oranges or orange juice. The participants were followed for 20 to 22 years.

During that time, 805 people developed Parkinson’s disease. In men, the top 20% who consumed the most flavonoids were about 40% less likely to develop Parkinson’s disease than the bottom 20% of male participants who consumed the least amount of flavonoids.

In women, there was no relationship between overall flavonoid consumption and developing Parkinson’s disease. However, when sub-classes of flavonoids were examined, regular consumption of anthocyanins, which are mainly obtained from berries, were found to be associated with a lower risk of Parkinson’s disease in both men and women.

“This is the first study in humans to examine the association between flavonoids and risk of developing Parkinson’s disease,” said study author Xiang Gao, MD, PhD, with the Harvard School of Public Health in Boston.

Fruit consumption has also been related to health benefits in a whole range of conditions including cancer, stroke, heart disease, diverticulosis, hypertension, cataracts, diabetes, asthma, and bronchitis.

Do you have any fruity stories to share?  SRxA’s Word on Health would love to hear from you.

To Give or Not to Give? – That is the question!

Few people in the respiratory community will have missed the study published last week in the New England Journal of Medicine (NEJM) that demonstrated Spiriva is comparable to Serevent in adults with uncontrolled asthma.

For those of you who did, SRxA’s Word on Health is pleased to provide you with a quick recap:

210 people with uncontrolled asthma were enrolled in a three-way, double-blind, triple dummy study.

All patients were treated with a beclamethasone inhaler (Qvar) to which was added Spiriva (tiotropium bromide), Serevent (salmeterol xinafoate) or a double dose of Qvar.

Results showed that Boehringer Ingelheim’s Spiriva, which is not currently FDA approved for asthma,  worked better than doubling the dosage of Teva’s Qvar and was just as effective as GlaxoSmithKline’s Serevent.

Interesting stuff, but in our opinion that was not the real news!

In an accompanying editorial, editors of the NEJM, chastised GSK for failing to provide free study drug to investigators from the National Heart, Lung, and Blood Institute. Apparently manufacturers were approached to supply both active drug and placebo inhalers, and while Boehringer Ingelheim (the manufacturer of tiotropium) and Teva (the manufacturer of Qvar) agreed to provide the materials, GlaxoSmithKline (the manufacturer of Salmeterol) refused.

The net result of this, say the editors was that investigators had to spend $900,000 from the National Institutes of Health (NIH) – and therefore they say, from taxpayers – to repackage the active drug and to create a visually identical placebo for use in the trial.

In a passionate conclusion to the editorial, Curfman, Morrissey and Drazen say:

“The most precious commodity that drug manufacturers possess is the trust of their research subjects, and to maintain this trust they need to be willing to put their products at risk. When they refuse to provide their drugs to legitimate investigators, the researchers will get their studies done without company help. It will take more time and cost more money, but in the end, the research will be done and the company will be perceived as having acted in its own self-interest rather than having worked to enhance the health of the community.”

This story was picked up by various news media who continued the vilification of GSK.

Here at Word on Health we’re not so sure that this criticism is justified.

First, pharmaceutical companies are not required to donate products for third party studies.

Second, Serevent is already licensed for the treatment of asthma. The company has previously performed numerous trials to demonstrate its efficacy and safety, including four studies on its effects in patients with asthma on concomitant inhaled corticosteroids.  In other words GSK did not need this study.

Boehringer, on the other hand did.

Two years ago, safety concerns were raised with Spiriva inhalers. Although the FDA has since said that recent data do not show a connection between the inhaler and previously reported risks of stroke, heart attack and death, doubts continued to linger in the market.  Additionally, as Spririva is not yet approved for use in asthma, any data that could show efficacy in this indication would potentially be an important step in gaining an additional licensed indication.

It is also worth noting that the total cost of the study was > $5.3 million. Tax payers money was being spent regardless.

And finally, it’s not as if Glaxo don’t pay their dues.  They are a member of the Partnership for Quality Medical Donations (PQMD), an alliance of pharmaceutical companies and humanitarian agencies that works to encourage the donation and timely delivery of appropriate medicines to people in need. They were one of the biggest donors of drugs and emergency medical relief following the monsoon floods that hit Pakistan in August; they have provided in excess of $1 million dollars of drugs to Haiti since the earthquake, more than $2 million to South East Asia. They also helped out following floods in El Salvador, wild fires in California, cyclones in Myanmar and the 2009 earthquake in China.

Should companies be forced to donate product to studies that are of no interest to themselves, or should they be free to spend the money and donate their product where they wish?

Should highly respected medical journals be allowed to single out companies for exercising their right to chose how they allocate their product?

Word on Health would love to know what you think.

In the interests of full disclosure we’d like to point out that none of the companies mentioned in this story are current clients of SRxA.

Hang on to your head! – New hope for migraine sufferers

Last week gene detectives revealed an important clue that could bring hope to millions of migraine sufferers worldwide.

After poring over the genetic profiles of more than 50,000 people, scientists announced that they had found the first inherited link to one of the most common types of the disease. This could be a huge breakthrough, both in terms of health, economics and quality of life.

Recent statistics from the National Institute of Health suggest that 11.7% of Americans (17.1% of women and 5.6% of men) suffer from migraines.  In Europe, the figures are reportedly even higher.  According to the World Health Organization (WHO), migraine is one of the top 20 diseases in terms of handicap. Indeed, a 2009 study put migraine’s economic cost on a par with diabetes.

Despite this, migraine is often perceived as a condition that imposes a minimal burden on society. Indeed sufferers are often accused of malingering.  These misperceptions persist, in part, because the disorder is episodic and rarely causes long-term physical disability. It’s also under-diagnosed and under-treated. As such, analyses of claims data underestimate the condition’s prevalence and economic impact.

In this latest breakthrough, scientists from 40 medical centers compared the genetic profiles of those who suffered from migraines with people who were otherwise healthy.  What they found was a tiny but telltale variant of DNA that boosts the risk of getting migraines by about a fifth.

“This is the first time we have been able to peer into the genomes of many thousands of people and find genetic clues to understand common migraine,” said Aarno Palotie, head of the International Headache Genetics Consortium.

Although previous research has found links for some extreme forms of migraine this is the first to pinpoint an association for common types of the disease.

The tiny genetic variant, or allele, is called rs1835740.

Lying between two genes on Chromosome 8, rs1835740 allows glutamate – a messenger chemical to accumulate in junctions between brain cells.  According to the team, accumulated glutamate then unleashes the migraine.  Although the authors say further work is needed to confirm the findings, if confirmed, all scientists have to do is find a drug that prevents glutamate build-up.

Easier said than done?  Only time will tell.

Meantime,  SRxA’s Word on Health would love to hear from you with your migraine stories and tips.

“Ouchless” Flu Vaccine

Instead of getting a BandAid after your flu shot, a new delivery patch could actually allow people to receive their vaccine this way.

The patches contain hundreds of tiny little needles, so small you don’t even feel them, that dissolve into the skin and release the vaccine. The result –  simplified immunization programs. By eliminating the use of needles and syringes, three of the biggest problems simply disappear.

• fear of needles
• disposal of leftover needles and syringes
• the need for trained medical personnel

The microneedle patches are applied like a BandAid and could allow self-administration of vaccine during pandemics as well as in schools and assisted-living facilities.  They could also simplify large-scale immunization programs in developing nations.

Researchers led by Professor Mark Prausnitz of Georgia Institute of Technology reported their research on microneedles in Sunday’s edition of Nature Medicine.

The business side of the patch apparently feels like fine sandpaper. In tests,  people rated the discomfort at 1/10th – 1/20th that of getting a standard injection. In other words, nearly everyone said it was painless.

The patch, which has been tested on mice, was developed in collaboration by researchers at Georgia Tech and Emory University. The work was supported by the National Institute of Health. The researchers are now seeking funds to begin tests in people and, if all goes well, the patch could be in use in five years.

Flu vaccination is recommended for nearly everyone, every year. According to Prausnitz, “Many people don’t get the shot because it’s inconvenient, but if they could get it in the mail or at the pharmacy they might do so.” The patch is placed on the skin and left for 5  to 15 minutes although it can remain longer without doing any damage.

Asked if the term “microneedle” might still frighten some folks averse to shots, Prausnitz said he was confident that marketers would come up with a better term before any sales began.

SRxA’s Word on Health challenges you to come up with some creative ideas.

Scientists Discover Allergy “Switch”

Word on Health was interested to learn that researchers from the University of Texas M.D. Anderson Cancer Center have found a molecule that specifically directs immune cells to develop the capability to produce allergic diseases such as asthma, eczema, and food allergy.  The study identifies thymic stromal lymphopoietin (TSLP) as a switch that causes the development of the allergic response.

The study team, led by Yong-Jun Liu, M.D., Ph.D., and supported by the National Institute of Allergy and Infectious Diseases, suggests that TSLP may be a potential therapeutic target to treat and prevent allergic diseases.

While this discovery is promising, leading allergy doctors have advised that it’s too early for allergy sufferers worldwide to start celebrating. “This is the latest in a long list of potential underlying causes for why some patients develop a harmful immunologic reaction to common, naturally occurring substances which are benign to the majority of people” cautioned Allan Luskin, MD of Madison, WI. “There have been many previous ‘pretenders’ which were thought to be responsible for this adverse immunologic response.  Much more data in needed before we can start talking about developing a therapeutic intervention”.

Dr. Michael Kaliner, Medical Director of the Institute for Asthma and Allergy, former head of Allergic Diseases at NIH and past president of the American Academy of Allergy Asthma and Immunology, and the World Allergy Organization, agrees.  He told Word on Health “Scientists keep searching for what makes an allergic patient exposed to an otherwise harmless protein, make antibodies, when non-allergic patients make no response whatsoever.  It is the ability to see and recognize an allergen in these ordinary substances that separates the allergic from the non-allergic population.”  Dr. Kaliner added, “If this factor is ultimately determined to be the factor instead of one of many, then it will be a viable target for therapeutic intervention”.

Meanwhile, only time will tell if TSLP is just another flash in the pan.