llumina executive chairman Jay Flatley used the mantle of receiving the Lifetime Acheivement Award at the Pesonalized Medicine Conference November 15, to frame his view of personalized medicine around the them of “shock and awe” in a keynote address.
“I’m in awe of what we’ve accomplished [in genomic medicine],” he noted, “but find it shocking that we’ve limited the use of these tools” through over-regulation and other systemic issues.
Flatley was introduced by Paul Billings, M.D., Ph.D. (a former competitor at Life Technologies), who described him as disruptive, smart, innovative, a job creator, and someone who has helped save many patient lives. “I’ve known Jay as a creative leader, a good listener, and a really good guy,” said Billings. Flatley dedicated his award to the 6000 Illumina employees.
Under Flatley’s leadership, Illumina emerged as the foremost genome-sequencing platform, having bought the British company Solexa in 2006. Flatley said the company’s instruments could sequence a human genome for as little as $800, and Illumina has “foreshadowed a path to the $100 genome” in the next few years. The Novaseq instrument can sequence one genome per hour.
Flatley began his speech by highlighting areas of immense progress and promise in personalized medicine. For example, he pointed to growing awareness of the role of the microbiome, which plays “a pivotal role” in shaping therapeutic response, neurological, and gastrointestinal diseases. “The potential to modulate these organisms is absolutely incredible.”
The CRISPR/Cas9 gene-editing technology points to a day in the future when it is possible to eliminate most genetic disorders. “CRISPR germline editing is likely inevitable, but caution on that front is well advised,” Flatley said.
Flatley also expressed awe at recent breakthroughs in therapeutics, noting 25 approved drugs are tailored to patient genetic profiles. “About 40% medicines in clinical trials could be classified as precision therapeutics,” said Flatley. In oncology, the figure rises to 75%.
Flatley hailed the recent FDA expanded approval of Merck’s Keytruda® (pembrolizumab), based on patients’ genetic signature, as “a major milestone in oncology treatment that will have profound implications.” He imagined a future world in which “the drug becomes the companion therapeutic to what will be a universal genetic test.”
Other areas of excitement include liquid biopsies and consumer genomics, areas in which Illumina has invested heavily with spin-offs, including GRAIL and Helix. “The speed of advancement in liquid biopsies is absolutely breathtaking,” he said. “We could someday replace a solid tumor biopsy.” GRAIL is developing a cancer screening test by collecting data from hundreds of thousands of patients in what would likely amount to “the world’s largest clinical trial.”
On consumer genetics, he said, “23andMe, Ancestry.com, and Helix are empowering consumers. They’re on a collision course with traditional medicine.”
A Way to Go
Despite progress on multiple fronts, enabled by genome sequencing, Flatley expressed concern that the potential of this technology wasn’t progressing faster. He recalled the story of a family friend who had recently been diagnosed with cancer. His local physician advised against biopsy DNA sequencing because “he didn’t think the results would be actionable.” Flatley expressed surprise and disdain and talked about the need for people to “age out.” Too many senior life science CEOs “are not skating to where the puck is going.”
Last year, he said, Illumina launched a 170-gene panel for cancer therapies and drugs in clinical trials. “But we can’t market it for diagnostic use because we don’t have regulatory approval. The work needed to demonstrate clinical utility is astronomical, and by the time we do that, [the panel] will be out of date.” (The panel is being used with pharma partners to help validate genes against experimental drugs.)
On reimbursement, Flatley noted that most genetic tests are PCR-based and examine only a few variants. It is “a nightmare for payers to manage,” he said. “Companies are encouraged to limit and underpower their products.”
Flatley asked rhetorically, “What is needed to shock this system to realize the promise of personalized medicine?” He added, “We need a new regulatory system.”
Returning to genomic medicine, Flatley saw huge promise in large-scale population genomics efforts to collect genomic and phenotypic data for both research and clinical application, supported by data federation and data sharing. The flagship project is Genomics England (GEL), which is a collection of 100,000 patients with rare diseases or cancer. The project committed to whole-genome sequencing three years ago. The pilot concludes at the end of 2018, and would become deeply embedded in the National Health Service.
In the United States, the rebranded “All of Us” initiative aims to collect data on one million people. But Flatley wondered whether this was sufficient. China is spending $9 billion to $10 billion on similar projects, he said, suggesting it would become “dominant, if not the dominant player in this century of biology.”
Imagine a World
Flatley concluded by painting a picture of the future era of personalized genomic medicine: “Imagine every baby sequenced at birth, part of their electronic health record, which is used to manage their health through their lifetime.” Screening would begin for early childhood diseases, including failure to thrive. Autism would be discovered early on. Later, as young adults, carrier screening would match the individual to his/her proposed partner. “If the odds [of a genetic disease] are high, in vitro fertilization and preimplantation genetic diagnosis allow the implantation of a healthy embryo,” producing “a healthy and happy family.”
If at age 42, the individual complains of “feeling punk,” the general practitioner could query a deep learning system for patient matches with similar symptoms. A genetic diagnosis could lead to a tailored therapy, and the patient could quickly get back to work.
Then at 65, a routine cancer blood test detects a cancer at Stage 0. Immunotherapy is prescribed, informed by microbiome sequencing to tailor therapy. “The doctor declares you cured in a month,” Flatley imagined.
“This may sound [like] a pipe dream to some, especially if you work in the medical system,” Flatley said. But when someone of Flatley’s stature and accomplishment says it, it’s hard not to believe it.