When CT Scan Fails to be a Cool Tool

Radiation on Spotlight

Hot, hot, and hot!  Wait, I am not referring to weather.  For those who may not know, in science community “hot” refers to “high” when it comes to radiation dose.  Recent full-body X-ray scan in the airport-screening procedure, increasing usages of the cone-beam CT scanners in dentists and orthodontists’ clinics, and damages caused by the CT head scan are all become news headlines.   With the advancement of radiation technologies in security and medical devices, more and more people start to worry about the trade-off between speed and scale of radiation scanners and dose and time of radiation exposure one receives.

Good News to Cheer

Lung cancer, one of the leading deadly cancers, causes ~157,300 deaths in the US alone.  Early discovery of small cancer tissue formation and surgical removal can prolong the lives of patients.  Recent good news revealed by the National Cancer Institute-sponsored clinical trial with over 53,000 participants (mainly smokers and ex-smokers) has shown that a 20 % reduction of mortality in participants screened by low dose helical CT scan instead of conventional chest X-ray.  Computed tomography (CT) scan utilizes radioactive atoms that emit X-rays to image detailed structures of a body.  The CT scan apparently has higher sensitivity, so it can lead to early detection and treatment.  However, CT scan is potentially a double-edged sword, warrant further study.

Bad News to Pay Attention

Although the CT scan has higher sensitivity than conventional X-ray, it also has high false positive (for lung abnormality) alarms, leading to unnecessary medical procedures and medication.  The CT scan is expensive with a price tag of at least $300 per screening.  The huge CT scan machine produces ~400 times higher dose of radiation compared with conventional X-ray.  In fact, experts have long been warning the FDA to regulate the CT scan on colon cancer screening due to its high radiation dose.  Now, there are several incidences whereby patients were severely hurt after high dose of radiation exposure, causing a variety of ailments, including hair loss, confusion and memory problems.

Proper Use of CT Scan is Crucial

What is the safest way to use CT scan and how?  There are many controversies among different interest groups, e.g. medical device makers, radiologists, patient advocate groups, insurance companies, and governmental regulators.  Each has its own stance on the risks and benefits of CT scan in prevention and diagnosis of various cancers.  Is there any ways to improve the safety of CT scan?  According to the FDA’s new release on preventing radiation overdose during CT scans, “education” becomes a key.  The CT scan manufactures need to better train the operators, because most overdose is a result of improper use of the scanner (i.e. operator error) not the machine malfunction.  When CT scan is properly used, it did not result radiation overdose.  I wonder why CT scan, such a sophisticated and expensive machine, was used with no clear and strict rules in the first place.  Now the FDA has stepped up to the investigation and followed up the cases of overdose, hopefully medical community is able to learn from past mistakes and seriously improve education, so the benefits of CT scan could outweigh risks of radiation exposure.

Until next post, keep on reading and writing!!

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Type 2 Diabetes Drug Faces Uncertain Future

Avandia is on The Hot Seat

Among a dozen diabetes medications, GlaxoSmithKline’s Avandia (rosiglitazone) has recently drawn scrutiny by the FDA due to adverse side effects on the cardiovascular system. To make matter worse, the company is being subpoenaed by the US Department of Justice over its development and marketing practices for Avandia over a decade.  In 28 October’s Nature reported that:

In its third-quarter earnings report released on 21 October, drug giant GlaxoSmithKline (GSK) revealed that it is being subpoenaed by the US Department of Justice over the company’s development and marketing practices for the diabetes drug Avandia (rosiglitazone). The company, headquartered in London, came under fire in July when a US Senate committee concluded that GSK had known about the drug’s heart risks for more than a decade without reporting them to regulators. GSK denied the charge. Sales of Avandia are currently restricted in the United States and banned in Europe.

Three Bad Luck Drugs in The Treatment of Type 2 Diabetes

Three similar diabetes drugs belonging to “thiazolidinedione” class, Troglitazone (Rezulin by Daiichi Sanyko Co.), Rosiglitazone (Avandia by GlaxoSmithKline) and Pioglitazone (Actos by Takeda Pharmaceuticals), help increase insulin sensitivity and are widely used in the treatment of type 2 diabetes.  Unfortunately, Rezulin was withdrawn from the U.S. market in 2000 due to hepatotoxicity.  Recently, Avandia was restricted for use in type 2 diabetes treatment due to increased heart attack and stroke risks.  Similarly, Actos was faced postmarket safety review of potential increased risk of bladder cancer.

Drug Effects Are Not That Easy to Study

From a biomedical scientist’s point of view, seeing those drugs crashed and burned is very frustrating.  On average, it costs ~$1.8 billion and 10- to 15-year timeframe to develop and bring a drug to market, let alone a possible withdrawal by FDA even after a drug goes on the market.  Why is it so hard to come out a safe and efficient drug?  In this case, I think the answers may lie in the undiscovered biological properties of cell membranes.  It’s been shown that small molecule’s perturbation to lipid bilayers (an essential component of cell membranes) can influence membrane proteins’ (e.g. ion channels, ion transporters, and receptors) functions.  The effects of above three famous bilayer-modifying molecules belong to “thiazolidinedione” class of drug acting as peroxisome proliferators-activated receptors gamma (PPARg) ligands that have multiple and profound effects on gene regulation, development, and metabolism.  In other words, these drugs somehow influence the cell membrane properties through complicated mechanisms, thereby causing functional changes of many unknown and unidentified targets.  In drug development world, the cost of “unknown” is very difficult to put a price tag on it.

Drug Development Business Seeks a Balancing Act Between Risks and Benefits

Again, no drug is perfect without any safety issue.  It’s a balancing act of the risks and benefits measurement and management.  When one drug flops, more will come; it is the failure we learn to make things better (hopefully)!

Until next post, keep on reading and writing!!

Companies Under The Radar of a Talking Head

Two of my previous blog posts mentioned the FDA’s decision on diabetes drugs’ fate, curiously and inevitably I also looked at the stock prices of the companies hammered or bolstered by FDA’s announcement.  Recently, a famous/infamous self-proclaimed financial guru talking head did a week-long report on several biotech/pharma companies facing upcoming FDA decisions or having new development reports in the conferences.  I thought for educational purpose, it is no harm to learn the characteristics of some diseases and drugs available on the markets.  No stock recommendation implied, buyers beware!

Multiple Sclerosis is a chronic multifactorial disease diagnosed in ~350,000 Americans in 2009 whose central and peripheral nervous systems, eyes, and bladder are affected.  Drug sales reach $10 billion and estimated number will reach $15 billion in the next 10 years.

  • Biogen Idec’s Avonex is an interferon beta-1a drug to slow down the progression of disability in MS patients.  Side effect of liver injury has been reported.
  • Merck Serono’s Rebif is also an interferon beta-1a drug.
  • Bayer’s Betaseron is an in interferon beta-1b drug for the treatment of relapsing remitting MS.
  • Teva Pharmaceutical’s Copaxone is a class of medications called immunomodulators.
  • Novartis’ Gilenya is a sphingosine 1-phosphate receptor modulator and has fewer side effects than Biogen Idec’s Avonex.

Type I and II Diabetes: In the US alone, 23.6 millions adults and children have diabetes, which accounts for 7.8% of population; by 2020, estimated 38 millions adults and children will be diabetic.

  • Sanofi-Aventis’s Lantus is once-daily injected insulin.
  • Amylin Pharmaceuticals/Alkermes/Eli Lilly’s Bydureon (once-weely injectable version of Byetta) was rejected by FDA on 10/19/2010 due to increased heart attack risk.  According to Bloomberg:

Lilly markets Byetta outside the U.S. and co-markets it with Amylin in the U.S. The drug was developed by Amylin, and the technology enabling it to be used in a longer-acting form was developed by Alkermes. Alkermes will receive royalties of about 8 percent on Bydureon sales.

Colorectal Cancer is the second leading cause of cancer death in the US.  It is estimated one-thirds of deaths could be avoided with early regular screening.  About 5 millions colonoscopies performed in the US this year, 30% of market shares could capture $1.2 billion.

Hepatitis C virus infection is transmitted by blood that affects about 3% (~170 million) people worldwide.  HCV infection is the most common cause of liver failure in the US.  No treatment is available and existing treatments made patients feel worse.

  • BMS/ZymoGenetics’s PEGylated-interferon lambda
  • Vertex Pharmaceutical’s Telaprevir
  • Pharmasset’s PSI-7977 is an oral uridine nucleotide analog polymerase inhibitor of HCV.
  • Merck’s Boceprivir is a protease inhibitor.

Orphan Diseases, also known as rare diseases, affect fewer than 200,000 people in the US.  There are estimated 5000-7000 orphan diseases existing worldwide.

  • Genzyme’s Cerezyme to treat Gaucher’s disease and Fabrazyme to treat Fabry’s disease.
  • BioMarin Pharmaceuticals’ Aldurazyme and Naglazyme are used for enzyme replacement for mucopolysaccharidosis.
  • Alexion Pharmaceuticals’ Soliris to treat rare, progressive, and life-threatening blood disease paroxysmal nocturnal hemoglobinuria.

Until next post, keep on reading and writing!!

A Different Kind of Direct Sale: Direct-to-Consumer Genetic Test

What is Direct-to-Consumer Genetic Test?

According to the National Institutes of Health’s (NIH) Genetics Home Reference website, direct-to-consumer (DTC) genetic test involves a direct to consumer marketing and sales tactics that bypass the engagement of the health care professionals such as medical doctors, nurse practitioners, or genetic counselors.  In general, consumers order test kits online or through mail, and send in requested samples back to companies; then the test results are sent directly to consumers with minimal consultation and interpretation from health care professionals.

Personalized Medicine Fuels The Development of The DTC Genetic Tests

When the alliance between the NIH-sponsored laboratories and Celera Genomics jointly announced the completion of sequencing the draft of the human genome in 2000, many have predicted the coming era of “personalized medicine”.  The idea is to develop and prescribe a treatment plan or drug based on the information encoding in each individual’s genome.  As a result, personalized medicine tailors individual’s intrinsic differences to improve diagnostics and treatment of diseases.  With the advancement of faster and less expensive DNA sequencing platforms, getting DNA information is easier than ever.  In a sense, the growing numbers of the DTC genetic test products are likely inspired by personalized medicine, a Holy Grail of future medicine.

Who Jumps on The Bandwagon of The DTC Genetic Test

It is a fast-growing market place for at home DTC genetic test that comes with garden varieties of selection. Tests include risk evaluation of diseases like Parkinson, Alzheimer’s, asthma, breast cancer, diabetes, gluten sensitivity, ancestry tracing, drug responsivity, and whole genome scan, etc.  So far, there are 20 companies receiving the FDA’s letters concerning their genetic test kits as medical “devices” that require data-driven regulatory review and postmarket monitor.

Can FDA Come Out a Win-Win Regulatory Policy?

Currently there are already many do-it-yourself at home tests on the markets, such as blood-sugar meter, home pregnancy test, or home colon-cancer-screening test kit, just to name a few.  So what is it so concerned about DTC genetic test?  It is crucial to understand that in all scientific measurements, there are intrinsic errors in sample selection/representation, technology platforms, or statistics inference.  One has to understand the perils of being misled or misinterpreted by the genetic test results, due to test errors (false positive or false negative), excessive claims (based on unproven study), or unrealistic risks/benefits.  It is time for the FDA to come out a clear regulatory policy to protect consumers from getting incorrect information and potential losing privacy, and at the same time to validate safety and effectiveness of company’s test device/kit as well as to monitor proper disclosure of risks and benefits of test results.

Until next post, keep on reading and writing!!

Fat Chance for Weight Loss Drugs

The Country in Desperate Need of Biggest Losers

Obesity has become a national image of the US population given that one in every three US residents (>72 millions) are overweight or obese. Compared with ~400 millions of overweight/obese human beings worldwide, 18% of them are in the US despite the fact that the US population only accounts for 4.52% of the entire population on earth.

Although it is fairly easy to tell if a person is overweight/obese, there is a scientific definition.  According to the Centers for Disease Control and Prevention, overweight is defined as the body mass index (BMI) is over 25 in an adult, whereas BMI greater than 30 is doomed obesity. Want to know your BMI? Click here to find out.  In addition to the severe distortion of body appearance by excess body fats, obesity can cause many notorious chronic diseases, such as diabetes, hypertension, heart attack, stroke, just to name a few (check this article to learn more diseases caused by obesity).

Losing is Simple But Not Easy

Obesity has created a huge market for biotech/pharmaceutical companies, from weight loss to lowering blood sugar, surgical fat removal to gastric bypass surgery.  Since obese patients are expected to rely on weight loss drug for a long period of time, it is conceivable that a FDA-approved magic pill can potentially become a cash cow for a pharmaceutical company.  Unfortunately, that magic pill is proved hard to find.  For instance, a fen-phen weight loss cocktail was recalled in 1997 due to serious heart and lung side effects.  On 8 October 2010, the FDA announced that Abbott Laboratories withdrew its 1997-approved weight loss drug Meridia off the market due to increased risk of heart attack and stroke.

During past few months, the FDA advisory committee had suggested “NO” to two companies developing weight loss drugs with unwanted side effects: Vivus’s Qnexa (phentermine and topiramate) and Arena Pharmaceuticals’s Lorqess (lorcaserin).  The next drug facing the FDA advisory committee, Orexigen and Takeda’s Contrave, is looking gloom given the recent FDA advisory committee’s tone on weight loss drugs.

Several companies with weight loss products still on the market are facing mixed sales records and potential side effects during aftermarket analysis.

  • GlaxoSmithKline: Alli
  • Roche: Xenical
  • Allergan: Lap-Band
  • Novo Nordisk: Victoza
  • Sanofi-Aventis: Lantus
  • Merck: Januvia
  • Eli Lilly/Amylin: Byetta

Go Back to The Basics

Although I am in the sickness industry (medical research to find the cause and cure for diseases), I really think the simplest way to reduce obesity incidence is to implement healthy diet and regular exercise promoted by the wellness industry.  Forget about that magic pill, eat right and sweat more!

Until next post, keep on reading and writing!!

A Plate of the Good, the Bad, and the Ugly

Tomorrow on 19 September 2010, the FDA’s Veterinary Medicine Advisory Committee will discuss and evaluate the safety, effectiveness, and environmental impact on the first genetically engineered (GE) Atlantic salmon called AquAdvantage from AquaBounty Technologies Inc. based in Waltham, MA.  So far, major news sources reported in an optimistic tone that AquAdvantage will receive recommendation from the panel.

Good: A New Biotechnology Makes Salmons Grow Bigger and Faster

With increasing growth of human population and unpredictable natural disasters on earth, there is an awareness of possible depletion of food source from the land and the sea in the future.  Since the inception of the recombinant DNA technology in the 70s, its variety of applications has benefited many industries like medicine, agriculture, and science, with humans being the biggest beneficiaries.  AquaBounty introduced a single copy of a continuously expressing growth hormone transgene into a salmon egg to produce triploid hemizygous all-female Atlantic salmon (Salmo salar).  Therefore, growth hormone was produced all year round, boosting the growth rate and mass of the GE salmons.  To ultimately resolve the decrement of naturally produced seafood, genetically engineered animals could offer a hope and solution.

Bad: Competition Between Nature vs Man-made

From the business point of view, for those whose livelihood rely on what the ocean can offer are concerning the competition brought by man-made fish, theoretically unlimited supply.

Ugly: We Don’t Know What We Don’t Know About GM Food

Speaking of genetically modified (GM) food, several of my colleagues reacted with doubts of potential unknown harm to the human population and environment.  Although there are strict FDA regulations of where and how the GE salmons can be cultured and distributed, a Nature News reader, Anurag Chaurasia of the National Bureau of Agriculturally Important Microorganisms in India, suggests:

“FDA should conduct SAFOTEST (by feeding GM fish to experimental animals) for few years followed by voluntary human trial before giving OK to transgenic fish.  There are always chance of cross breeding between GM & wild fish.  More ever in biology it is not always 1+1=2, some may not be triploid.  FDA should not be in a hurry in such sensitive issue otherwise GMOs like opposition may have to be faced.”

There are also other concerns about food allergy or increased cancer risk from consuming a large amount of GE food.  So the post-market data collection and analysis has to be implemented to allow us understand the potential hazard (or lack of) of GE food.

Until next post, keep on reading and writing!!

Take a Thrill Ride of the FDA Advisory Panel’s Decision

Gambling on FDA Advisory Panel Decision?

I recently encountered a short article on how to use FDA’s advisory panel to trade stocks. The article caught my eyes because I am really curious about how Wall Street plays games using FDA.

Pump and Dump Prelude?

My case-in-point is VIVUS, a biopharmaceuticals company whose weight management drug QNEXA (phentermine/topiramate) faced the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee’s vote whether it can go on market on July 15.  On July 13’s Wall Street Journal, a report “FDA Finds ‘Significant’ Weight Loss With Qnexa” and New York Times’s “F.D.A. Review of Diet Pill Relieves Investors” both had positive outlooks for QNEXA to pass panel vote to go on market.  And Leerink Swann analyst Steve Yoo told Reuters, “The topics the FDA raised are in line with what we expected,” and he said “the likelihood of a positive panel vote has increased, which in turn increases the likelihood of approval.”  Three major news sources were upbeat about QNEXA’s clinical trial results.

Science Speaks Louder

To give myself a benefit of doubt, I went to FDA’s website to download over 200 pages document.  I have to admit that I am not experienced enough to make a judgement call, but there are many safety issues that seem to be not negligible.  On July 15, the FDA panel rejected QNEXA due to its questionable safety issues.  Admittedly, share price of VIVUS tanked during after hour trading.

What do I learn from this case?  Timing is everything and beware of analyst’s opinions.  Because some information may not be toxic on the surface, inside it can poison you if you don’t do your own due diligence and give a benefit of doubt on things you don’t really understand.  There are more cases you can practice as many drugs are waiting in line for FDA advisory panels’ examinations.

[Disclosure: I don’t own any of the stocks in the articles I provided the links to, and I don’t endorse any strategies of trading stocks.]

Until next post, keep on reading and writing!!