Genome sequencing will be a routine diagnostic test for patients at the new Institute for Precision Medicine in New York City, a joint project of the Weill Cornell Medical College and NewYork-Presbyterian Hospital. Doctors will be searching for new genetic clues about disease by taking an unbiased survey along the genome, rather than scanning only for genes already known to cause illness.
Using next-generation sequencing equipment from San Diego-based Illumina, the researchers are aiming to find new treatment options for cancer, neurodegenerative disorders, and cardiovascular disease. But a companion goal is to persuade health insurers to reimburse for the cost of sequencing the genomes of individuals, says Mark Rubin, the director of the institute, which was founded this year.
“Right now in the current climate, it’s not clear how that’s going to happen,” says Rubin, an expert pathologist who has explored genetic factors in prostate cancer. “We’ll have to cover the cost.”
Rubin hopes, over time, to demonstrate to health plans the value of capturing a fuller picture of individual genetic factors, which may guide doctors to prescribe drugs they wouldn’t otherwise have considered. The Institute will use the Illumina sequencers to get a readout of what’s called the “exome.” This is an important subset of the genome containing all the genes that code for the manufacture of proteins—those workhorse biological molecules behind most of the operations of a living cell.
Rubin’s new research center is joining an ecosystem of medical, academic, and commercial players that together are nudging health insurers toward coverage for broader genetic scans of individual patients. Researchers have shown that diseases such as breast cancer can arise from different genetic mutations in different patients. Pharmaceutical companies are using genetic insights to design their drugs, and to identify the patients most likely to benefit from them. The result is a tailored approach to treatment often referred to as “personalized medicine” or the newer term “precision medicine.”
Multi-gene scans are becoming a more common tool to match an individual with the best treatments, whether or not the drug has yet been approved for that patient’s illness. This is particularly true in cancer, where many new drugs have been designed to block specific molecular mechanisms, and those mechanisms may be found in more than one tumor type. Scientists are also characterizing the array of mutations that can contribute to complex diseases like autism and cancer.
Doctors are starting to order tests such as Cambridge, MA-based Foundation Medicine’s assay of more than 236 genes linked to cancer. Physicians can also get clinical exome tests for diseases such as autism from Ambry Genetics of Aliso Viejo, CA.
At Ambry or Silicon Valley Biosystems (SV Bio) of Foster City, CA, doctors can order exome sequencing to ferret out possible genetic causes of unexplained symptoms, such as seizures or loss of verbal ability, that doctors haven’t been able to diagnose. Gene sequencing is sought for patients suffering from such “mystery diseases” that have not been identified through extensive testing by other means.
Health insurers are already covering an array of tests to assess specific genes as a guide to treatment. For example, one assay tests breast tumor tissue for an abnormal number of copies of the Her2 gene, which codes for a protein that promotes cell growth and division. This genetic mutation can also be detected by testing for abnormally high levels of the Her2 protein itself. A positive result on either of these tests means a woman is more likely to benefit from Roche’s drug trastuzumab (Herceptin). U.S. health plans spent an estimated total of $5 billion on such genetic and molecular diagnostic testing in 2010, according to a study by UnitedHealth Group. By 2021, such expenditures could rise into the range of $15 billion to $25 billion, the study authors predicted.
That said, reimbursement can be difficult to secure even for a limited test checking a single gene, if payers don’t see proof of the test’s value. Insurers ask whether a test is essential to help doctors choose a treatment; whether the test improves patient outcomes; and even whether it delivers economic benefits such as lowering the overall cost of healthcare.
That makes the hurdles even higher for sequencing hundreds or thousands of genes across an individual’s genome, says Edward Abrahams, president of the Personalized Medicine Coalition.
“The insurance industry is waiting to see demonstration of clinical utility,” Abrahams says. “This is where the tension is.”
For the time being, many patients are paying out of pocket for broader genetic screening tests. But companies such as Ambry and Foundation Medicine are helping doctors make a stab at getting the cost reimbursed by billing health plans directly. Sequencing technology maker Illumina now also offers its own test for patients, called TruSight Individual Genome Sequencing, but leaves it up to patients and their doctors to seek repayment from health plans. Whether insurers pay or not, they’re now evaluating claims that wider genome scans are a medical necessity in some cases.
In the meantime, researchers and companies can draw on financial resources other than reimbursement to fund DNA scans for individual patients. Mark Rubin at New York’s new Institute for Precision Medicine says he’ll seek charitable contributions to help pay for the tests. The institute will also help run clinical trials for companies including Cambridge, MA-based Millennium, a unit of Japan-based Takeda. Foundation Medicine also has revenue-producing collaborations with drug companies.
Together, all these entities are amplifying knowledge about the genetic causes of illness by building up biobanks of individual gene sequences and tracking patient outcomes when treatment is guided by genetic clues. Rubin says the cumulative proof will eventually lead to reimbursement for genome sequencing.
One factor that may speed up the reimbursement timeline is the plummeting cost of genome sequencing, says Dietrich Stephan, the CEO of SV Bio. The cost of sequencing a whole human genome is now close to the current price range of reimbursable diagnostic tests that search for just one gene, or a few specific genes.
“One can make the argument with a straight face that it’ll be cheaper for a lab to sequence the genome rather than sequencing a single gene,” Stephan says.
It’s possible that in the near future, diagnostic labs will scan the whole genome or the exome no matter what particular genes a doctor wants to look at for diagnostic purposes, he says. It may be more cost-efficient for labs to run a single type of test rather than maintaining the ability to perform dozens of different tests of various smaller selections of DNA, Stephan says.
In 2001, it cost about $100,000 to sequence a single human genome. Illumina now charges researchers $4,000 per genome, if they run 50 or more samples. And Illumina’s genome sequencing service for individual patients, which includes a detailed interpretation, cost $9,500 when the patient doesn’t qualify for a subsidy program.
The price for a more limited exome sequencing is in the hundreds of dollars, Stephan says. Health plans may begin to see value in broader genome scans rather than piecemeal genetic tests to answer specific questions, he says. With a genome scan, a fuller range of information on the patient’s DNA will be stored in case a new medical problem crops up.
“I have no doubt that genome testing will be driven into routine practice within a five-year time frame,” Stephan says.
One possible future scenario is that genome or exome scans will be cranked out by commercial diagnostic labs such as Quest and LabCorp, which will then turn over the sequences to firms like SV Bio to interpret the results, Stephan says. His Bay area company is already operating on this model. SV Bio offers exome sequencing with a full interpretation for about $5,800. But it will also evaluate sequences done by other labs. And it will take doctors’ requests for limited interpretations focused only on the genes that are relevant to a specific disease afflicting their patients.
Even if Stephan’s predictions about the genomic testing market bear out, the evolving field will still have room for specialized genetic testing. In cancer diagnosis, for example, investigators test the tumor tissue to see which mutations have arisen to cause the cells to grow uncontrollably.
Foundation Medicine, rather than running an exome scan or full genome sequencing of tumor cell DNA, zeroes in on 236 genes that are implicated in cancer, says Kevin Krenitsky, the company’s chief commercial officer. That narrower focus allows the company to probe more deeply into other genetic factors that influence those cancer genes, causing rearrangements or repetitions of certain DNA sequences, for example. The Foundation One test, launched in June, will be constantly updated as new genetic knowledge flows from research centers such as the Institute for Precision Medicine.
The test has been ordered by more than 700 oncologists, and has uncovered novel genetic links in cancer, Krenitsky says. The genetic scan revealed alterations in the Her2 gene in tumors other than breast cancer, he says. Health plans have covered the cost of some treatments suggested by the test. But getting the Foundation One test itself reimbursed is a further hurdle. Foundation Medicine is compiling patient case studies and other data to establish the clinical value of the test, and is already making presentations to health plans, Krenitsky says.
Abrahams of the Personalized Medicine Coalition says the cancer field may open the door to more routine reimbursement of broader genome screening. Sequencing of tumor tissue is becoming a common practice at certain academic medical centers, he says.
“I wouldn’t say it’s the standard of care, but it’s likely to become so in the next few years—in cancer,” Abrahams says.
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