Avastin Hits the Breast Cancer Indication Wall

A Brief History of Avastin

Avastin (its generic name: bevacizumab) was developed by the biotechnology giant–Genentech (bought by Roche in March 2009), and was first approved by the U.S. FDA in 2004.  Avastin is a biologic antibody targeting “vascular endothelial growth factor” that involves in blood vessel formation.  By disturbing the blood vessel formation (a.k.a. angiogenesis) in tumors, the tumor cells lose nutrition and oxygen supplies and therefore die.  Avastin, in combination with intravenous 5-fluorouracil-based chemotherapy, has been used in treatment of several solid tumors, like metastatic colorectal cancer, metastatic kidney cancer, and non-small cell lung cancer.  In addition, in combination with paclitaxel (another chemotherapy drug), Avastin was used in treatment of metastatic HER2-negative breast cancer patients.  Unfortunately, the new clinical data from US trials showed that Avastin is not effective.  Based on the new scientific data, the FDA recently had decided to recommend removal of breast cancer indication from Avastin label.

Contrary Results of Avastin in Breast Cancer Treatment

Initially, I was grieved by Avastin’s failure of showing benefits in disease-related symptoms or survival to breast cancer patients.  But turn on my glass is half-full thought, at least Avastin is still valid in other treatment indications.  However, Genetech, the company marketing the drug doesn’t think so because the European Medicines Agency gave a green light to Avastin, arguing against FDA’s recommendation of Avastin removal from breast cancer indication.  Genentech will request a hearing with FDA by 18 January 2011.

Some Sticky Issues in FDA’s Decision on Avastin

In 2008, Avastin was granted “accelerated approval” for metastatic breast cancer treatment in combination with paclitaxel (called E2100 study).  Few years later, more science-based evidence from two clinical trial studies (named AVADO and RIBBON1) showed that Avastin did not benefit breast cancer patients.  Some patients claimed Avastin is helpful and are afraid the FDA’s decision will affect Medicare reimbursement because the annual spending of Avastin can reach $88,000, not many patients can afford such expensive treatment if Medicare doesn’t pay for it (or part of it).  You can read more on:

Until next post, keep on reading and writing!!  Happy New Year 🙂

The FDA Takes on the Food Safety Policing Role (Soon?)

Sick from Food? Not Rare Anymore

People from the place I grew up used to joke about the food that sold by street vendors: not clean enough but won’t get you sick.  Most of the time, the food materials were produced locally and prepared right in front of you; if you don’t feel comfortable about the sanitary condition of the food preparation process, you just don’t buy it.  If you do get sick, though it was not that common, come back to complain and ask for improvement or compensation.  Most food vendors operate on the ethical and moral basis–make food for the customers the way they make their own food.  Good reputation will serve their small businesses well by word-of-mouth.  Now, time has changed.  With the industrialization of food production and distribution, food-borne illnesses have increased in the numbers of outbreak and on a bigger and broader scale.  Recent Salmonella contaminated eggs causing nearly 2000 illnesses is just the tip of the iceberg.

Something about Legislation You Need to Know

On 30 November, the US Senate passed a law on food safety that renders the U.S. Food and Drug Administration (FDA) a bigger muscle to stop unsafe food reaching to consumers.  Although the food safety bill was passed by the US Senate, it may or may not eventually become a law.  According to Nature News, the food safety bill will require further negotiation between the Republicans and Democrats.  Go figure!

The bill could conceivably be defined to raise taxes, by imposing fees on food importers and on domestic manufacturers whose food is subject to a recall when it is discovered to be tainted. If those fees are defined as taxes, then, under the US Constitution, the bill must first be passed by the House of Representatives. The House passed a food safety bill in July, 2009, but it is different than the Senate version — meaning that, for the Senate bill that was passed on Tuesday to become law, it must first be voted on by the House, and then again passed by the Senate, before being signed into law by the president.

Beyond the FDA’s Policing Power on Food Safety

Have you ever seen a car running red light or speeding but no police around to catch it?  Have you ever wondered the traffic lights, signals, and signs are good enough to keep cars and pedestrians safe?  The traffic safety enforcement is only as useful as the people who actually obey it.  Likewise, I think the FDA’s new food safety regulatory power will only be effective when all parties, including farmers (produce, meat, egg, milk, etc.), food production and process companies, food inspectors, importers/exporters, and consumers, agree to cooperate to achieve the same goal–food safety to all humans and animals alike.

Food Safety Issues Appearing in the Media

A while ago, one of my co-workers lent me a book called “In Defense of Food: An Eater’s Manifesto” by Michael Pollan.  My eyes were wide-opened by several examples of how our nutrition was compromised by industrialized food process.  In conjunction with recent food safety legislation, I also recommend several media reports about food safety and regulations:

Until next post, keep on reading and writing!!

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!!

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!!