With the highest-profile seller of $99 genetic tests under fire, will public trust in personalised medicine suffer, an ethicist wonders

IT'S 2008. The New Yorker is chronicling a celebrity "spit party", at which notables nicknamed the "Spitterati" eject saliva into tubes to find out their risk of developing illnesses such as diabetes, heart disease and cancer. The firm involved is 23andMe, a direct-to-consumer genetic testing company whose service was named Invention of the Year by Time magazine.

Fast-forward five years. 23andMe receives a demand from the US Food and Drug Administration (FDA) to stop selling its health-related tests pending scientific analysis. In a separate event, a Californian woman, Lisa Casey, files a $5 million class action lawsuit alleging false and misleading advertising. 23andMe suspends sales of its test, putting paid to its target of reaching 1 million customers by the end of 2013. Where did it all go wrong?

In November, after what the FDA describes as years of "diligently working to help [23andMe] comply with regulatory requirements", the agency sent a scathing letter to the firm's CEO Anne Wojcicki. It stated that 23andMe's Personal Genome Service was marketed without approval and broke federal law, since six years after it began selling the kits, the firm still hasn't proved that they work.

Doubts go back a long way. In the year of the spit party, the American Society for Clinical Oncology commissioned a report that concluded the partial type of analysis involved wasn't clinically proven to be effective in cancer care. In 2010 the US Government Accountability Office concluded that "direct-to-consumer genetic tests [involve] misleading test results... further complicated by deceptive marketing".

What 23andMe offered was a $99 test for 250 genetically linked conditions, based on a partial reading of single-nucleotide polymorphisms (SNPs). These are points where the genomes of different individuals vary by a single DNA base pair. There are some 3 billion base pairs in the human genome this test targets only a fraction of them. Different companies sample different SNPs and so return different results for the same person.

To illustrate this point, in his book Experimental Man, science writer David Ewing Duncan recalled how he received three conflicting assessments of heart attack risk from three different companies. The director of one, deCODEme no longer offering such tests telephoned him from Iceland to urge him to start taking cholesterol-lowering statins. Yet the other two tests one from 23andMe, one from Navigenics, which no longer offers consumer tests had rated him at medium or low risk. Given that some statins carry side effects such as muscle weakness, Duncan might have been ill-advised to follow deCODE's urgent advice.

This is the root of the FDA's concerns. In its letter to 23andMe, it raised the risk that customers could get false information that leads to drastic and misguided medical steps. Wojcicki now says: "We want to work with [the FDA], and we will work with them." But is it too little, too late?

And what of the class action lawsuit, brought by Casey after buying a test? It focuses on the test's accuracy but goes further, targeting what Casey's attorney calls "a very thinly disguised way of getting people to pay [23andMe] to build a DNA database".

By asking customers to fill in surveys about health and lifestyle, 23andMe has been creating a valuable "biobank" for patenting purposes and industry collaboration. The firm has always sought customer consent for use of identifiable data and hasn't disguised its aim. "The long game here is not to make money selling kits, although the kits are essential to get the base level data," says 23andMe board member Patrick Chung. "Once you have the data, [23andMe]... becomes the Google of personalised healthcare."

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Testing times for the consumer genetics revolution

PUBLIC RELEASE DATE:

13-Jan-2014

Contact: Haley Bridger hbridger@broadinstitute.org 617-714-7968 Broad Institute of MIT and Harvard

The most comprehensive genetic study to date of the blood cancer multiple myeloma has revealed that the genetic landscape of the disease may be more complicated than previously thought. Through results published in Cancer Cell today, a team of Broad researchers has shown that an individual patient's tumor can harbor populations of cancer cells equipped with different mutations. These findings could have therapeutic implications for patients in the future.

"What this new work shows us is that when we treat an individual patient with multiple myeloma, it's possible that we're not just looking at one disease, but at many in the same person, there could be cancer cells with different genetic make-ups," said co-senior author Todd Golub, the Broad Institute's Chief Scientific Officer and Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute. Golub is also a professor at Harvard Medical School and an investigator at Howard Hughes Medical Institute. "These findings indicate a need to identify the extent of genetic diversity within a tumor as we move toward precision cancer medicine and genome-based diagnostics."

In a detailed study of samples from more than 200 multiple myeloma patients, Golub and colleagues identified frequent mutations in several key genes known to play an important role in cancer including KRAS, NRAS, and BRAF. But they found that many of these telltale mutations were not present in all cancer cells within a tumor instead, they were often found in only a smaller fraction of cells, known as a subclonal population.

Many promising cancer therapies used in treatment today target a specific genetic mutation. This new work suggests that such targeted therapies may have limitations in patients whose tumors are made up of these subclonal populations.

The research team performed follow-up experiments in the lab to explore some of the therapeutic implications, looking specifically at BRAF, a cancer gene for which several inhibitors, or drugs, exist. Previous studies indicated that around four percent of multiple myeloma patients may have mutations in this gene, and a recent report on a single multiple myeloma patient treated with drugs targeting BRAF showed promising results. BRAF inhibitors have also been used to treat patients with melanoma and other forms of cancer. In the lab, however, the research team found evidence that treating a tumor harboring subclonal BRAF mutations with one of these targeted drugs may at best kill a fraction of the cells, and at worst, stimulate another cancer cell subpopulation to grow.

"There's clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others," said co-first author Jens Lohr an associated scientist at the Broad and a medical oncologist at Dana-Farber. "If a patient has a BRAF mutation in less than 100 percent of his cells, or if he has mutations in KRAS or NRAS at the same time, his oncologist would want to think through the potential pitfalls before giving the inhibitor."

Resistance or the ability for tumors to shrink and then grow back has become a major hurdle in treating patients with targeted therapies such as BRAF inhibitors. The new research suggests that subclonal populations could be one of the potential reasons many patients suffer relapse after treatment.

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Multiple myeloma study uncovers genetic diversity within tumors

Washington, D.C. (PRWEB) January 13, 2014

The Food and Drug Administrations new approach to personalized medicine was sent in motion on November 22, 2013 with its warning letter to 23andme regarding the provision of personal genetic information to customers.

The FDA found that 23andmes offering to be a device that was intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease and that in certain circumstances it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing action. Accordingly, the FDA found 23andme in violation of the Federal Food, Drug and Cosmetic Act by marketing its product without acquiring prior approval from the FDA.

Zecola explains that such an approach is misguided for several reasons:

1) The provision of personal genetic information is just that, an information service. The FTC, not the FDA, has jurisdiction over information services in determining whether they are fraudulent. 2) The action is paternalistic and impinges upon personal liberty. The personal genetics companies include disclaimers on their websites and materials saying that their customers should not take action on the personal genetic information but rather should consult with a certified healthcare practitioner before taking any action. 3) The FDAs action, in effect, protects the status quo and undermines the potential for innovation in personalized medicine. 4) The FDA hasnt explained how it could carry out in a timely manner the massive amount of tests that it says is required for the personal genetic firms to provide information to their customers. Its track record suggests that it would take years to analyze and rule upon the upwards of a million tests that are being run by personal genetic firms.

Zecola argues that rather than protecting the status quo from new technology, the Department of Health and Human Services and its subsidiary Food and Drug Administration should be reorganized to better focus on how technology can be used to improve health care.

In essence, the burden should be on the FDA to improve its efficiency to match the exponential growth of technology, rather than constraining the gains from technology to the processing capability of the FDA.

The article is available at http://www.TheFDAandYou.com.

For additional work by the author describing how government should better manage science and technology, see The Major Forces Driving Humanity: Solutions for a Growing Divide (2008). Also see Obama Needs Better Tools to Drive Lasting Change (December 24, 2008).

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Author and Entrepreneur Steven Zecola Highlights the Fallacies of the FDA’s Approach to Personal Genetic Information

Genzyme, a Sanofi company (SNY: Quote), and Alnylam Pharmaceuticals, Inc. (ALNY: Quote) Monday said they have significantly expanded their strategic agreement to develop and commercialize treatments for rare genetic diseases. As part of the expanded relationship, Genzyme will invest $700 million to become a major Alnylam shareholder.

Under the new agreement, Genzyme will have significant rights to Alnylam's portfolio of clinical and pre-clinical stage drug candidates.

Alnylam will retain most product rights in North America and Western Europe, and will have significantly expanded development and commercial opportunities for its genetic medicine pipeline through Genzyme's established global infrastructure in rare diseases.

David Meeker, Genzyme's President and CEO, said, "This collaboration is an important building block for our future. It strengthens our pipeline and provides us with the opportunity to meet the needs of patients with rare diseases around the world through our well-established global organization."

In 2012, Alnylam and Genzyme formed an exclusive alliance to develop and commercialize Alnylam's lead product, patisiran, which is in Phase 3 development for the treatment of transthyretin or TTR-familial amyloid polyneuropathy, a rare life-threatening disease that damages the nervous system.

In the new alliance, Alnylam benefits from Genzyme's proven global capabilities, enabling the firm to accelerate and expand market access for its 'Alnylam 5x15' products.

In the new relationship, Genzyme will obtain expanded rights to patisiran. Under the original agreement from 2012, Genzyme had rights to commercialize patisiran in Japan and the broader Asia-Pacific region where this disease has a disproportionately high prevalence.

Under the expanded agreement, Genzyme will now commercialize patisiran in all territories outside of North America and Western Europe, which are retained by Alnylam for their commercialization.

Secondly, Genzyme will obtain rights to commercialize worldwide three products in Alnylam's pipeline. Genzyme and Alnylam will co-develop and co-commercialize ALN-TTRsc, a product currently in Phase 2 development for the treatment of familial amyloid cardiomyopathy, in North America and Western Europe, while Genzyme commercializes the product in the rest of world.

Genzyme will have the rights to two additional products after the completion of early clinical trials. The firm will be able to choose between full global rights or co-commercialization rights, depending on the product.

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Genzyme Expands Alliance With Alnylam Pharma, To Invest $700 Mln For 12% Stake