http://www.forbes.com/healthcare/200...0418genes.html

Regulation
States Crack Down On Online Gene Tests
Robert Langreth and Matthew Herper 04.18.08, 6:00 AM ET


The flashy new industry of personalized gene testing is experiencing some early blowback.

Over the last six months, New York State's Department of Health has sent letters raising the specter of fines and jail time to six online gene-testing firms that offer consumers the ability to peer into their genome to assess their future risk of getting diseases such as cancer, heart disease and multiple sclerosis. Often, it turns out, the services offering these DNA deep-dives are doing so without the involvement of a doctor. That puts them on the wrong side of the law.

Targets in New York's letter-writing campaign include the high-profile 23andMe, in Mountain View, Calif, (run by the wife of Google co-founder Sergey Brin) and Navigenics, of Redwood Shores, Calif., as well as their publicly traded partners Illumina and Affymetrix. The letters say the companies cannot perform their gene scans on New York residents without a permit. Warning letters to three more online gene-scanning firms are due to go out soon, New York says.

California health regulators are also investigating 12 complaints from the public about certain online gene testers. California won't name the targeted companies, but notes that in the state "all genetic tests must be ordered by a licensed physician." Overall, 24 states prohibit or limit so-called direct-access testing without a doctor or other medical professional's involvement, according to a 2007 survey by Johns Hopkins University's Genetics & Public Policy Center.

These new online services allow consumers to order genetic tests over the Web with a credit card. Consumers get a kit in the mail and send it in with a cheek swab or spit sample. The results are posted a few weeks later on a secure Web site. Navigenics, Iceland's DeCode Genetics and 23andMe, whose investors include Google and Genentech, use DNA chips to give people preliminary data on their risk of a variety of diseases. DeCodeMe and 23andme also offer info about how your genes relate to physical traits such as bitter taste perception.

Both 23andMe and DeCode, which has not received a warning letter from New York so far, argue that the lab testing laws don't apply because their products are not medical tests. "23andMe's services are not medical ... they are educational," argues 23andMe spokesman Paul Kranhold.

That argument doesn't mean spit to the New York regulators, who are concerned about the reliability of the online tests and their potential to send people rushing to their doctor demanding a cure for a fatal disease they may never get.

"Frankly, it blows my mind that someone would be saying that looking at whether you are going to get multiple sclerosis is recreational," says a New York official who spoke on condition of anonymity. The official says New York is not about to shut the services down but, "we would refer them to the attorney general's office" if they continue to operate in violation of the law.

Navigenics is putting New York residents on a waiting list to avoid flouting the law until it can get a permit. It says its $2,500 service differs from many others because it includes consultations over the phone with a genetic counselor to explain what the results mean. Navigenics employs a doctor who officially orders tests for consumers. 23andMe said that it would employ doctors if state regulators require it; it said it was in "active dialogue" with New York.

The clash highlights the fragmented regulatory environment for bespoke genotyping. The Food and Drug Administration has left it up to the states to decide what's permissible without a doctor's approval. "Basically everybody's trying to figure out what the regulatory environment is going to be for this consumer stuff," says Jay Flatley, Illumina's chief executive. "What's a diagnostic? What's not a diagnostic? And it's tricky."

Complicating matters is the fact many online gene testers, including 23andMe and Navigenics, don't actually perform the scans themselves; they are simply Web portals that disclose the results of tests performed by contract labs. "There are very few federal regulations in this area," says Elliott Stein, an attorney who represents gene-tester HairDx, which just received a letter from New York. "Unfortunately for these companies, they've got to deal with the regulations in each and every state, and often that is a judgment call."

One worry is that people who order online gene tests could get misleading information. For example, 23andMe tests for some gene variants involved in mildly raising breast cancer risk, but not genes called BRCA1 and BRCA2 that vastly raise breast cancer risk. Harvard Medical School's Mark Daley says if you found out that you had genes that slightly reduced the risk of cancer, but didn't check for the real cancer-causing gene like BRCA1, "you get a potentially dangerously misleading answer."

DeCode seems to be trying to have it both ways. The Icelandic company's diagnostics unit sells tests for gene variants that boost risk of diabetes, heart attack and other diseases. These single-disease tests are ordered through a doctor and are not available to New York residents because DeCode's lab is not licensed in the state.

However, New York residents can also get their whole genome scanned for $985 through DeCode's DecodeMe Web site. This service tests for 26 different disease-promoting genes and traits, including some of the same variants in its doctor-prescribed tests. What's the difference? "We don't believe [DecodeMe] requires licensing because it is not a medical test," a Decode spokesman explains. "It is very clear it is not a medical thing." New York health officials said they were not aware that the DecodeMe service was available in New York.

Some commentators argue that the wild-west business of gene testing needs more regulation, lest abuses discredit the whole industry before it has a chance to thrive.

In a recent commentary in Science, Kathy Hudson, director of the genetics and public policy center at Johns Hopkins University, points to several diagnostic companies that screen genes involved in drug metabolism to determine how to dose antidepressants. Some of these companies are making claims that haven't been proven in clinical trials, she says. She noted that one lab operator, Genelex, states on its Web site that its test is "required to effectively prescribe Paxil." In a press release, Genelex said that the quote was taken out of context, and that trials were ongoing.

Genelex Chief Executive Howard Coleman defends his test. He says that folks inside the beltway have a knee-jerk reaction towards calling for new regulations, instead of enforcing laws already on the books, such as those against false advertising.

Hudson calls for a mandatory public registry of all gene tests to allow consumers a better sense of what they're paying for. "Without that, there are bound to be bad actors that enter the marketplace because the barriers to entry are so low."

http://www.affymetrix.com/support/te...any_3_2008.pdf

Marshfield Clinic Research Team Uses Affymetrix DMET Solution to Discover Genetic Variant Affecting Warfarin Metabolism in Patients
Results to Help Improve Drug Dosing Dilemma and Reduce Risks of Adverse Reactions

SANTA CLARA, Calif. & MARSHFIELD, Wis.--(BUSINESS WIRE)--Feb. 7, 2008--Affymetrix Inc. (Nasdaq:AFFX) and Marshfield Clinic today announced that researchers at Marshfield Clinic used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) solution to discover a genetic variation associated with an individual's response to the drug warfarin.

The study, "CYP4F2 genetic variant alters required warfarin dose," was published this week by Blood Online. The results of the study could help reduce much of the serious adverse events caused by incorrect warfarin dosage and enable doctors to treat patients with a more effective, personalized form of medicine.

The team of scientists, led by Michael D. Caldwell, M.D., Ph.D., of Marshfield Clinic, discovered a genetic variation in a gene called CYP450 4F2 (CYP4F2) that explains approximately 8 percent of a patient's variable response to warfarin. The discovery was made possible because of the DMET solution, which is the industry's most comprehensive method for assaying the genetics of drug metabolism. Marshfield has already begun testing the result in a prospective Phase III clinical trial expected to be completed by the end of 2008 and funded by the Agency for Healthcare Research and Quality (AHRQ).

"This discovery should enable us to better predict a stable therapeutic dose and hopefully reduce the overall complications of warfarin therapy," said Dr. Caldwell. "Understanding the factors and genetic variations that affect the metabolization of drugs gives doctors a much more accurate idea of how best to treat patients. The nation's entire healthcare system can benefit from these types of advances."

In August 2007, the U.S. Food and Drug Administration (FDA) announced that they would be updating the labeling of warfarin with known valid markers in the CYP2C9 and VKORC1 genes to provide information on how an individual's genetics may impact their response to the drug. The use of warfarin is complicated due to its small therapeutic index window of dosage. If a dose is too high, there is a risk of bleeding; if a dose is too low, the drug will be ineffective and there may be a risk of clotting. The optimum dosage is affected by factors such as genetics, age, body mass index and gender.

"Marshfield Clinic has one of the world's largest and best characterized patient populations for warfarin treatment and we are thrilled to collaborate with them to help solve this dosing problem," said Maneesh Jain, senior director of marketing at Affymetrix. "This study is an example of the power and ability of our DMET solution. Clinical researchers are now able to take a comprehensive look at all of the drug metabolism biomarkers, which will enable clinicians and pharmaceutical scientists to develop safer and more effective treatments."

In January, Affymetrix launched its DMET Early Access solution, an updated version of the assay used in the Marshfield warfarin study. Pharmaceutical customers are using the DMET solution to better understand pharmacokinetics, the study of the bodily absorption, distribution, metabolism and excretion (ADME) of drugs. DMET is the only product available with comprehensive coverage of all ADME drug metabolism biomarkers. It profiles more than 1,069 drug metabolism biomarkers, including 172 "core" genetic markers. Data is automatically interpreted into a common format that can be integrated into clinical trial workflows. The information enables researchers to make more informed drug-development decisions, which in turn significantly streamlines the drug-development process and, therefore, the time to market.

For more information the Affymetrix DMET Early Access Solution, please visit: http://www.affymetrix.com/genechip/DMET.affx

About Marshfield Clinic

The Marshfield Clinic system provides patient care, research and education with more than 40 locations in northern, central and western Wisconsin, making it one of the largest comprehensive medical systems in the United States. For more information about Marshfield Clinic, visit: http://www.marshfieldclinic.org

About Affymetrix

Affymetrix GeneChip(R) microarray technology is the industry-standard tool for analyzing complex genetic information. After inventing microarray technology in the late 1980s, Affymetrix scientists have been dedicated to developing innovative products that provide researchers with a more complete view of the genome. These products continue to accelerate genetic research and enable scientists to develop diagnostics and tailor treatments for individual patients by identifying and measuring the genetic information associated with complex diseases.

Today, Affymetrix technology is used by the world's top pharmaceutical, diagnostic and biotechnology companies, as well as leading academic, government and not-for-profit research institutes. More than 1,600 systems have been shipped around the world and more than 10,500 peer-reviewed papers have been published using the technology.

Affymetrix is headquartered in Santa Clara, Calif., and has manufacturing facilities in Sacramento, Calif., Cleveland, Ohio, and Singapore. The company has about 1,100 employees worldwide and maintains sales and distribution operations across Europe and Asia. For more information about Affymetrix, please visit: www.affymetrix.com.

Forward-looking Statements

All statements in this press release that are not historical are "forward-looking statements" within the meaning of Section 21E of the Securities Exchange Act as amended, including statements regarding Affymetrix' "expectations," "beliefs," "hopes," "intentions," "strategies" or the like. Such statements are subject to risks and uncertainties that could cause actual results to differ materially for Affymetrix from those projected, including, but not limited to: risks and uncertainties relating to commercial success of the collaboration between Affymetrix and Marshfield Clinic discussed in this press release; risks of the company's ability to achieve and sustain higher levels of revenue, risks related to past and present acquisitions, higher gross margins and reduced operating expenses; uncertainties related to technological approaches, manufacturing and product development; personnel retention; uncertainties related to cost and pricing of Affymetrix products; dependence on collaborative partners; uncertainties related to sole-source suppliers; risks associated with acquisitions; uncertainties relating to FDA and other regulatory approvals; competition; risks relating to intellectual property of others and the uncertainties of patent protection and litigation. These and other risk factors are discussed in Affymetrix' Form 10-K for the year ended December 31, 2006, and other SEC reports, including its Quarterly Reports on Form 10-Q for subsequent quarterly periods. Affymetrix expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Affymetrix' expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

CONTACT: Affymetrix Inc.
Andrew Noble, 408-731-5571 (Media)
Assoc. Director, Corporate Communications
Doug Farrell, 408-731-5285 (Investors)
Vice President, Investor Relations
or
Marshfield Clinic
Teresa Derfus, 715-387-9362 (Media)
Media Relations Manager

SOURCE: Affymetrix Inc.

http://investor.affymetrix.com/phoen...cle&ID=1105493

http://www.wired.com/medtech/genetic...12/ff_genomics

http://www.thegeneticgenealogist.com...dme-revisited/

http://tinyurl.com/3nprtt

05 | 14 | 2008 Posted By Kristie Prinz
DNA Testing: Should Private Companies be able to Conduct DNA Tests Outside without Physician Input?
A legal issue is brewing between companies conducting at-home DNA testing and some state governments, which object to the fact that these companies are conducting such tests without state permits and/or physician supervision, according to a report by Forbes.

Forbes reported on the issue as follows:

New York State's Department of Health recently sent letters raising the specter of fines and jail time to 23andMe, its competitor Navigenics, their partners Illumina and Affymetrix, and five other gene-testing outfits. The state says they can't do their scans without permits. (Navigenics says it uses a licensed doctor.) California is investigating 12 public complaints about certain mail-order gene testers.

In Maryland a health department official frets that self-prescribed gene tests have "serious potential for causing harm" if misinterpreted. Overall, 24 states prohibit or limit certain testing without a doctor's involvement, according to the Johns Hopkins University's Genetics & Public Policy Center.


Should the states have the ability to regulate gene testing, and should that regulation require the supervision by a licensed doctor? This question raises some interesting public policy issues.

As a consumer, if I were to pursue gene testing, I am not sure that I would want such testing run through a physician, since in all likelihood, that would mean that the test results would end up in the hands of my insurance company, whereas, if I paid a company privately for such tests, the information is more likely to remain private. My preference would be to have the tests privately run and then take responsibility myself for ensuring that the appropriate medical tests were run subsequently to screen for whatever illnesses that the testing had indicated I would be genetically inclined to catch.

In contrast, I am sure that a physician's perspective would be that a physician needs access to the results in order to better treat the patient. The physician might argue that the results are worthless unless the physician has access to the information. He or she might even argue that it is not in the patient's best interest to be told the results without having a physician there to interpret the data or to offer some support as needed.

I am interested in hearing what the blog readers have to say on this issue: should private companies be allowed to run gene screening tests privately without being regulated by the individual states and without requiring that the tests be run under a physician's superivision? If you have any comments on this issue, please pass them along and we will post them to the site.

There is little doubt that this debate is going to continue to receive attention in the near future as gene testing increases in popularity. We will keep you posted here at the California Biotech Law Blog as the debate further develops.

http://www.forbes.com/forbes/2008/05...ech_newsletter

http://www.forbes.com/video/?video=f...haeljfox011008

Genetics
ImClone's Gene Test Battle
Robert Langreth 05.16.08, 6:00 AM ET


ImClone Systems' breakthrough colon cancer drug Erbitux has become a billion-dollar best seller as a one-size-fits-all drug for patients who have failed treatment with chemotherapy.

But emerging new gene findings indicate that the high-priced drug may be useless in nearly half of colon cancer patients--and that a simple gene test could allow doctors to predict in advance which patients are likely to benefit. The drug, co-marketed by ImClone and Bristol-Myers Squibb, costs $38,000 for a four-month course of treatment.

The result is one of the first examples of personalized medicine in colon cancer. It helps explain why tumors shrink dramatically in a minority of patients who get the drug while most others get little benefit. The new gene test could allow doctors to give the drug only to patients who are likely to benefit, and avoid those who are likely to just get side effects. Side effects of the drug include skin rashes and infections in the fingers and toes.

A series of studies published over the last several months indicate that about 35% to as much as 45% of colon patients probably should not be taking Erbitux or a similar drug from Amgen called Vectibix. These patients have tumors with a mutation in a growth-promoting gene called kras that may render the drugs ineffective.

Erbitux and Vectibix are antibodies that bind to receptors on the cell surface called EGF and blocks signals that turn kras on. But the mutations apparently cause kras to become permanently stuck in the "on" position. Although the results are still preliminary, this appears to eliminate the possibility of benefiting from the drug.

"It is the first 'thou shalt not' gene marker in colon cancer," says Memorial- Sloan-Kettering colon cancer specialist Leonard Saltz, a pioneer in testing Erbitux. He calls the data "unbelievably airtight." ... "Thou shalt not give Erbitux and Vectibix to patients with mutated kras; all it will do is give toxicity and run up the bill." Memorial started testing colon cancer patients for kras early this year.

"Largely what personalized medicine will be is telling people which drugs are out there that don't work so don't bother. This is the first step in that direction," Saltz says. That won't be good news for some patients who find out they have one less treatment option, he admits. "But it is reality, and you can look at it or stick your head in the sand."

One French study published in the Jan. 20 Journal of Clinical Oncology found that none of the 24 patients with kras mutation responded to Erbitux, while tumors shrank in 40% of those with normal kras. In another study by researchers in Belgium published in March, Erbitux worked in none of 42 patients with the mutation, but 27 of 66 patients without it. Amgen has published a big study showing that its Vectibix only works in patients with normal kras. In Europe, Vectibix is only approved for patients who have normal kras.

Larger trials are needed to confirm the Erbitux results. But UCLA's Jonsson Cancer Center is also in the process of gearing up to perform the kras gene test, says J. Randolph Hecht, who directs the gastrointestinal oncology program there. "We don't want to expose people to drugs that won't benefit them."

The emerging results could throw the colon cancer drug market in turmoil. Bristol-Myers and ImClone could lose a significant chunk of sales as doctors stop using it in patients with the gene mutation. But Erbitux may also gain sales if doctors start using Erbitux earlier on in the course of the disease in those with normal version of the gene. This could slice into sales of Genentech's Avastin drug, which is currently a mainstay of initial treatment for metastatic colon cancer.

How this will wash out over the long run isn't clear at the moment.

M.D. Anderson Cancer Center's Scott Kopetz says that about one-third of his colon patients, ones who lack the mutation, are now getting Erbitux as an initial treatment instead of Avastin. "The holy grail is trying to identify which patients will benefit," he says. If there is any benefit of the drugs in those with kras mutations, "it is exceedingly small," he adds.

"It is potentially a very big breakthrough," says Bristol-Myers Vice President Martin Birkhofer. He predicts that the finding could expand the use of Erbitux in patients who do not have a kras mutation. But he says the company will follow the science even if it means many patients who would have gotten the drug in the past no longer get it.

Back at Memorial Sloan Kettering, Saltz believes it is premature to start giving Erbitux instead of Avastin to patients. There is no proof that using Erbitux up front can keep people alive longer than using Avastin, even in those with normal kras. Meanwhile, Erbitux is not currently FDA approved for initial treatment of colon cancer, and insurers could balk at paying for earlier Erbitux use.

Much more data on kras will be presented at a big meeting of cancer doctors in Chicago at the beginning of June that could clarify the matter once and for all. In particular, researchers will re-analyze a previous big trial of Erbitux as initial colon cancer treatment to see if the drug combo worked better in the subset of patients who don't have kras mutations.


http://www.forbes.com/business/2008/...16imclone.html