Included in BioWorld's list of the most impactful stories in 2015, which will be published later this month, is the expansion of the global activities in precision medicine. While the field has been growing for some time, boosted by cloud computing and big data analytics, it officially received its stamp of approval and funding boost in January following President Obama's launch of the Precision Medicine Initiative (PMI), a research effort designed to pioneer a patient care model to accelerate the shift to personalized medicine.

In effect, the nation has been challenged to draw on its vast technological and scientific resources to develop next-generation medicines and diagnostics faster and more efficiently than the present rate of innovation. It is a huge task and the clock has started ticking.

However, that is not the first time that genomics and personalized medicine have taken center stage, Back in June 2000 President Bill Clinton and U.K. Prime Minister Tony Blair hailed the completion of the draft of the human genome as the starting point in profound new knowledge giving humankind new power to heal. "Genome science will have a real impact on all our lives – and even more, on the lives of our children. It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases," said Clinton.

They noted that in the coming years, doctors increasingly will be able to cure diseases like Alzheimer's, Parkinson's, diabetes and cancer by attacking their genetic roots.

There is no doubt that the time horizon they envisaged to see tangible results would have been comparatively short.

Francis Collins, for example, who back in 2000 was director of the NIH's National Human Genome Research Institute, addressed the Human Genome Project and how its outcomes would impact the future of medicine at the second annual National Congress on the Future of Genomics, Biotechnology and Pharmaceuticals in Medical Care. (See BioWorld Today, Nov. 20, 2000.)

"Virtually any disease except trauma will have some hereditary contribution if you look hard enough," Collins said. "Even an infectious disease like AIDS has some genetic contributors that have an effect on whether you become ill after exposure to a particular viral or bacterial agent. So whatever disease you are interested in unraveling, genetics offers a very powerful set of tools to peer into the most primary basis of what is going on in that condition. The ultimate goal of genomics is to develop therapies that you couldn't have with another strategy."

In the year 2020, Collins predicted that technology being developed at that time would enable scientists to develop gene-based designer drugs that will enter the market for a long list of diseases. "Others may say the 2020 prediction is too conservative, and I certainly hope so."

NOT PLAYING OUT AS EXPECTED

Unfortunately, the full impact of the Human Genome Project didn't play out according to the way it was predicted 15 years ago – a fact acknowledged by Collins, now director of the NIH, during a talk to kick off the Personalized Medicine & Diagnostics track at the BIO 2015 International Convention in Philadelphia in June. (See BioWorld Today, June 22, 2015.)

Collins affirmed that he was delighted the PMI had received bipartisan support. He did, however, remind his audience that it was not a new idea and that, in 2004, he had called for an ambitious large-scale, long-term trial that could provide information on how environmental factors influence many common diseases.

The idea, Collins said, did not find support at the time because the technology needed to realize the promise of precision medicine, which focuses on the individual rather than an "average" patient, wasn't available.

In fact a decade after the initial enthusiasm on the hailed dawn of the genomics era questions were being raised in the industry and the media about whether it had lived up to its promise. Next-generation new disease cures had been expected, and on that front the period had been a bitter disappointment.

Five years on from those criticisms, the technology has continued to evolve rapidly, providing renewed hope that the PMI will, finally, be the stimulus to accelerate drug discovery and genomics delivering on its promise.

Collins noted in his keynote talk that finally the stars appear to be aligning to move forward with the initiative. Notably, the cost of human genome sequencing continues to fall and is approaching the magic $1,000 mark, a far cry from the massive $100 million price tag 15 years ago; electronic health records, while still a work in progress, have also become more prevalent, along with an expanding array of mobile monitoring technologies; and the development and utilization of big data projects are contributing new insights into the genomics of various complex diseases.

Those advances have put the proposed two main components of the initiative – a focus on cancers and a longer-term aim to generate knowledge applicable to the whole range of health and disease – well within reach.

The near-term cancer component of the initiative will test precision therapies in collaboration with private sector partners and expand current understanding of therapeutic response. The second component provides a long-term structure to generate a knowledge base to move precision medicine to health and disease more broadly by building a national research cohort of 1 million or more volunteers and supporting research to develop and test technology and mobile health approaches. The participants will be asked to give consent for extensive characterization of biologic specimens and behavioral and environmental data all linked to their electronic health records.

To realize the ambitious goals of the PMI, the public has to "buy in" and be willing to share genetic and medical data. That support is vital and the future of precision medicine depends on a positive response.

Collins indicated that the public is enthusiastic about the initiative and the research cohort project has a good running start since it will be assembled using some existing cohort studies that have already collected data.

The NIH hopes to have patients begin to enroll in the early part of 2016.

With $200 million funding in place, the near-term cancer project can accelerate levering relevant studies already under way and ramp up the genomic analysis component considerably.

The initiative also will support clinical trials, in partnership with pharmaceutical companies, to test combinations of targeted therapies that are based on a tumor's molecular signature. It also plans to develop solutions to drug resistance that commonly limit the effectiveness of targeted therapies and develop approaches that can assess response to therapy.

DATA, DATA, DATA

There is no doubt that the project will contribute an enormous amount of data. Therefore, being able to harness and mine the utility of big data will be critical for innovative drug development going forward. Yet reducing massive databases into byte-sized pieces that are both meaningful and actionable represents an enormous leap, and we are only just beginning to figure out how to take the first steps in that process.

To that end, the NIH has established the Big Data to Knowledge Centers of Excellence program designed to improve the ability of the research community to use increasingly large and complex datasets through the development and distribution of innovative approaches, methods, software and tools for data-sharing, integration, analysis and management.

Also, because more and more medical and research centers are sequencing the DNA of whole genomes, millions of DNA differences in genes and the regions between the genes are detected. However, doctors struggle to know which of those variants are relevant to disease and to a patient's medical care. As a result, their utility isn't very high, Collins said. That is why the Clinical Genome Resource (Clingen) is being developed where investigators will design and implement a framework for evaluating which variants play a role in disease and finding those that are relevant to patient care. Those experts will, in effect, assign levels of confidence to the information of the various variants that are identified.

The FDA has also been working on how big data solutions will cope with more than 80 million genetic variants that may or may not affect a person's health or risk of disease. (See BioWorld Today, Aug. 7, 2015.)

Enter precisionFDA, a cloud-based approach to advanced genomics research that provides the big data analytics foundation to support personalized medicines. Launched this month, it is a planned community that will create an environment for next-generation sequencing test developers, researchers and others to work together to test, pilot and validate new approaches, advancing the science to develop the standards and tools that will serve as the infrastructure for precision medicine. While the precisionFDA project notes it does not serve a regulatory role, it is expected to generate knowledge to inform future regulatory pathways and decision making.

Daryl Pritchard, vice president, science policy at the Washington-based Personalized Medicine Coalition, commented, "PrecisionFDA is an encouraging effort to engage the personalized medicine community in its decision-making processes. Keeping up with scientific advancements in personalized medicine is difficult, but FDA is addressing the challenge."

With big data now taking center stage in the whole drug discovery ecosystem, expect to see significant progress in precision medicine in 2016 and beyond. Maybe Collins' prediction for the market roll-out of gene-based designer drugs for a long list of diseases by 2020 won't be far off the mark after all.