Imagine walking into the doctor’s office for a physical exam and, while you’re there, you get a simple blood test that maps your genetic history, revealing personal health risks and how you might respond to various treatments were you to get sick.
That’s not the case today, but it could be in the future as scientists and medical researchers develop easier and less costly ways of sequencing and analyzing patients’ genomes. Still, much needs to change within the world of regulations, reimbursement and data sharing for precision medicine to become widespread.
The human genome was first sequenced in 2003, and with that came the possibility of creating new medicines and treatment strategies that are tailored to an individual’s specific needs. Biopharmaceutical and biotech companies, as well as researchers in academic medical centers, have been working hard since then to realize that dream, but to date few breakthroughs have occurred.
President Obama’s Precision Medicine Initiative, announced just over a year ago, aims to speed things up. Out of a total $215 million budgeted for fiscal year 2016, $130 million was allocated to the National Institutes of Health to build a million-person cohort of personalized data that would extend the promise of precision medicine to all diseases.
At a summit on the topic this morning, President Obama is expected to release incremental steps that'll seek to assist customized individual treatments.
And this year, the president will ask Congress for $755 million to fund cancer research — Vice President Joe Biden’s so-called cancer “moonshot” — with part of the funding targeted at improving genomic analysis of tumors and surrounding cells.
That's a large database
At some medical facilities, genomic testing is already becoming a way of life. Under the Profile project, all patients who come to the Dana-Farber Cancer Institute, Brigham & Women’s Hospital and Boston Children’s Hospital with a diagnosis of cancer have their genome profiled. The information is used to guide physicians in determining the best care for each patient, but also goes into a large database that can link genomic results to clinical outcomes.
The project just completed its 10,000th genomic profile and is averaging 400 to 500 a month. “This is rapidly becoming one of the largest databases of its kind in the world,” said Barrett Rollins, chief scientific officer at Dana-Farber and head of the Profile project.
Setting up a broad-based genetic profiling program presented a number of technical challenges, Rollins said. Ensuring that profiles could be done on archived issues, such as biopsies, required rebuilding some of the hospitals’ ordering and reporting systems. And there was the sheer volume of tests that were being done. In the next couple of months, the project expects to add germline sequencing, and that will require different workflows, he said. As a result, the plan is to initially focus on four or five specific diseases.
While low-hanging fruit may be picked, the industry is far from dried up
Industry is getting into the act, too. In the past five years, biopharmaceutical companies have doubled their R&D efforts in precision medicine, comprising 42% of all drugs in development, according to Booz Allen Hamilton. But the logistics of precision medicine could temper the extent to which big pharma embraces the field.
“If you look at it at face value, it’s going to be really difficult for these very large companies that want to make drugs with fairly large returns” to recover costs of developing precision medicines because the market is potentially much smaller, said Tim Andrews, vice president of Booz Allen’s health team and a member of the precision medicine team. “There will have to be different kinds of [business] models about how things are done.”
Rollins agrees. Fifteen or 20 years ago, drugs were developed almost exclusively by pharmaceutical and biotech companies, but the genomics revolution has taken large markets and chopped them up into small ones, he said. “There may be as many as 20 different kinds of lung cancer, and each one may require a different drug.” Today, the balance has shifted and universities and research institutions are doing more of the early-stage design and then partnering with drug companies later on to develop the drug and run clinical trials.
The other reason for the shift, Rollins believes, is that much of the low-hanging fruit has already been picked. “Just on a chemical basis, some targets are easy and some targets are hard … and the hard ones require more cost for a company,” he explained. But for academics, that difficult target “is why they get up in the morning.”
Smaller players are vying for space in precision medicine market, too. Earlier this month, Carlsbad, CA-based Sure Genomics launched a service that lets people take a saliva test at home, mail it to the company and get a full DNA sequence. Initial reports will focus on the BRCA1 and BRCA2 breast cancer mutations, drug response and interaction, fitness and nutrition, traits and ancestry, but the firm plans to add more reports as FDA clearance is obtained.
And in January 2015, Hospital Corp. of America’s cancer enterprise, the Sarah Cannon Research Institute, announced a partnership with software developer Synapse to provide molecular profiles of patients at its 75 U.S. cancer centers. The data is uploaded on Synapse’s platform where it can be tracked and compared.
Innovation not without challenges
But there have been missteps, too. Theranos, the media darling which promised to revolutionize the diagnostics industry with cheap finger-prick blood tests, has been cited by both the FDA and the CMS for deviations at its Newark, CA, laboratory. The issues raised questions about the accuracy of Theranos’ results and implications for patient safety.
There are also real challenges facing the precision medicine movement. While the cost of sequencing a genome has dropped significantly, from around $100,000 in the early 2000s to about $5,000 today, experts agree that wide-scale use of it is unsustainable without reimbursement. But there are questions such as how to reimburse for individualized treatments and the need for outcome data that supports use of genomic testing.
Dana-Farber’s Profile project spends about $6 million a year on testing, all of it paid for by philanthropy. The institute is currently in a pilot study with Blue Cross and Blue Shield of Massachusetts to attempt to tie reimbursement to clinical outcomes.
Regulators will also need to keep pace with the advances in precision medicine. The FDA recently launched a cloud-based platform where the various stakeholders can exchange information and compare results.
There are also issues with data sharing and interoperability, said Andrews. With all of this data piling up in various databases, how do you unify that and what do you do with data from a clinical trial, for instance, when a drugmaker abandons the drug? There also are still arguments over whether a gene should be patentable.
To improve data sharing, Dana-Farber and six other cancer research institutes in the U.S., Canada and Europe founded Project Genie to combine their sequencing data and, following a six-month exclusivity period, make it available for anyone to use. The program — established under the auspices of the American Association for Cancer Research — went live with 17,000 sequencing cases and expects to grow that database to 200,000 cases in five years.
Ask Rollins about the promise of precision medicine, and he points to small, but notable changes that are occurring. At Dana-Farber and its sister hospitals, the profile test that all cancer patients now get is what doctors are requesting and what they act on, he said. “It’s a real example of the practicality of doing these broad-based genomic tests and how they’re going to work in routine clinical care.”
And there are personal success stories as well. Rollins notes the case of a dying young man who came to the institute for a second opinion on leukemia that had failed earlier chemotherapies. When he took the routine profile test, it showed a “totally unexpected result” that predicted his leukemia would be sensitive to a specific pill, Rollins said, allowing him to be treated and eventually undergo a bone marrow transplant. Today, he and his wife are expecting their first child.
Still, precision medicine is still very much in its infancy. With 30,000 or 50,000 important genes, “genetics is just a blueprint,” said Andrews. “There are perhaps tens if not hundreds of thousands of proteins that are generated by those genes and make us run, and so there’s that whole next level of proteomics and epigenetics.” To really advance precision medicine, all of these things really need to come together.