Trend: Advanced Diagnostics and Precision Medicine


Contributed by:

Denise Myshko

Healthcare is moving increasingly toward personalized approaches — tailoring treatment based on each patient’s unique disease. Precision medicine is well-established in oncology, with many cancers now characterized by their unique genomic alterations. In the past few years, the Food and Drug Administration has approved several treatments based on an individual’s genetic makeup or genetic variants of his or her disease.

Since the first personalized medicine approval for HER2 positive breast cancer in 1998 — Genentech’s Herceptin — there have been major breakthroughs happening every year across multiple disease indications, from autoimmune disorders to genetic conditions to cancer. Advances in precision medicine, with new diagnostics and new therapies that allow for even greater precision are expected to continue.

An example of the advancements taking place is the 2017 FDA approval of Merck’s Keytruda, which was based on the genetic profile of a tumor, rather than the tissue or tumor type.

Industry leaders say the FDA’s approval for Keytruda for all solid tumors with microsatellite instability (MSI) high status, regardless of location within their body, underscores the need to identify the molecular changes that drive a patient’s cancer to identify a potential benefit from immunotherapy, and highlights why the industry needs to move toward comprehensive genomic profiling.

This research was done in collaboration with researchers at Johns Hopkins, which had been working on cancers that have gene mutations that regulate DNA.

“In collaboration, we performed a study involving patients with different types of cancer who all carried the unique mutation in DNA repair gene, which can be detected by a commonly available mismatch repair test,” says Eric Rubin, M.D., head of early oncology development, Merck Research Laboratories. “It turned out these identified patients responded quite well to Keytruda, which ultimately led to receiving breakthrough designation from the FDA, and ultimately approval from the FDA. Keytruda is the first example of a drug that was approved on the basis of a genetic alteration in the cancer rather than a particular cancer type.”

Precision medicine is an integral part of Merck’s development strategy, Dr. Rubin says.
“Before a molecule ever enters the clinic, we strive to understand the appropriate tests to identify patients who are likely to respond,” he says. “This is no doubt true for many companies, as we now recognize the importance of tests to identify patient need. This step happens very early in the development process.”

On the day PharmaVOICE spoke with Dr. Rubin, two researchers were awarded the Nobel Prize in Physiology or Medicine for their basic research that identified immune-based targets. Working separately, James P. Allison and Tasuku Honjo demonstrated how different strategies for inhibiting the brakes on the immune system could be used to treat cancer. It was Dr. Honjo’s research of PD-1, a protein on T cells that stops the immune system from attacking cancer, which informed the development of Keytruda.

Keytruda and other PD-1 inhibitors work to block the PD-1/PD-L1 pathway and prevent cancer from hiding from the immune system.

Taking the Measure of Precision Medicine

Precision medicine is the idea of applying the right treatment to the patient’s situation, says Ilan Danieli, CEO of Precipio. “If we don’t have a picture of the patient’s clinical situation, precision medicine falls apart. The starting point is understanding the genetic footprint of the patient — understanding what the biology of the tumor is — in order to apply the proper treatment.”

He says diagnostics will play an even greater role in the future because it won’t be used just as an up-front, one-time tool, but rather as an ongoing tool to assess the biology of the tumor as it changes and evolves.

The promise of real-time oncology treatment would be to monitor a patient daily or weekly, to detect the recurrence of the cancer at a very early stage, and be able to tailor or change treatment to prevent a full-blown recurrence, says Rachel Laing, managing partner, Bionest Partners. “The tools to enable this therapeutic approach are being developed and improved as we speak — liquid biopsy, next-generation sequencing, digital tools to track a patient’s response and symptoms — and will be critical to fully achieve the promise of precision medicine.”

Ms. Laing says finding ways to manage the data generated from these measurements will be just as critical: technologies to amass, analyze, and execute meaningfully large amounts of data are needed.

“We have already moved, in many instances, from measuring one gene via PCR to measuring a panel of genes by next-generation sequencing,” she says. “Lastly, we are likely to see an integration of digital technologies, be it to improve R&D efficiency, help with clinical trial management and recruitment, or improve patient management and treatment tailoring.”

Big data is poised to accelerate development and innovation in precision medicine, says Jackie Kent, senior VP, global head of product, Medidata Solutions.

“The velocity and variety of data are accelerating in clinical trials, making integration and standardization more complex,” she says. “In addition, precision medicine takes into account individual variability in genes, environment, and lifestyle, greatly increasing the complexity of the clinical trial design as compared with the one-size-fits-all approach taken in traditional drug development. Relevant clinical trial data solutions are needed to ensure advancements in precision medicine are efficient and cost-effective.”

But few companies have been able to capitalize on the promise of precision medicine. Doing so requires a dramatically new set of capabilities.

We have come a long way, but we’re not quite there yet, says Melanie Nallicheri, chief business officer and head, biopharma, Foundation Medicine. “Many clinical trials use retrospective analyses to determine the value of biomarkers, and it will be important to conduct more prospective trials to determine predictive value of new types of biomarkers. I expect that the complexity of the underlying biomarkers will change over time and the technologies we will be using will evolve as well.”

She says Foundation Medicine will add gene expression profiling to its understanding of the underlying biology and leverage these insights to develop new biomarkers.

Comprehensive genomic profiling, Ms. Nallicheri says, can save time and precious tissue for advanced cancer patients. “Single biomarker tests using common diagnostic techniques such as PCR, IHC, and FISH, and multigene hotspot NGS tests, don’t always identify genomic alterations, which could be critical to a patient’s treatment plan. In addition, sequential single biomarker testing may result in tissue exhaustion before all disease-relevant genes have been tested.”

Dr. Rubin points out that for Keytruda’s tissue-agnostic approval, the tests used during the trials — one involved detection of proteins, a common method known as immunohistochemistry, and another is a DNA-based test that involved the polymerase chain reaction — were not FDA approved at the time for the purposes that Merck wanted to use them.

“They were commonly used to detect alterations that can be inherited, particularly in colon cancer,” he says. “The FDA has required a postmarketing commitment to pursue these approved tests, and one of our diagnostic partners in the space is Foundation Medicine.”

With the growing number of diagnostic tests available on the market, it’s becoming increasingly more complex for researchers and physicians to identify patient treatment options, says Elizabeth Hans, business strategy manager, Accenture Life Sciences.

“Physicians not only need to understand the number of tests available to them, but also how the tests work, what they identify, and how to read the results in order to make critical decisions for their patients’ treatment options,” she says. “A recent study in the Washington Post reported that out of 100 physicians surveyed to gauge their understanding of the risks and benefits of 10 common tests, 80% of the physicians overestimated the benefits. This complex space requires more involvement from patients, researchers, and companies to ensure the right treatment decisions are being made for patients.”

The Future Promise of Precision Medicine

The global precision medicine market was valued at about $43.59 billion in 2016 and is estimated to reach $141.7 billion by 2026, according to BIS Research. The market is expected to grow at a compound annual growth rate (CAGR) of 11.23% between the years 2017 and 2026, aided by the adoption of early diagnosis, increased number of adverse drug reactions cases, high prevalence of chronic diseases, and advancements in genetic science, among other market drivers.

Precision medicine involves a detailed study on patient-specific information to diagnose and characterize disease. The concept of precision medicine is rapidly growing in the medical community through the tremendous expansion of various advanced technologies, such as next-generation sequencing, molecular biomarker analysis, bioinformatics, and big data analytics, among others.

By applying a deeper understanding of diseases with richer patient data and advanced analytics, precision medicine can help physicians tailor treatments to the needs of individual patients once they get sick, rather than applying standard treatments determined by broader populations.

Industry leaders say with the entrance of big tech companies into the health space, such as Apple and others, we are now closer than ever to collecting personalized information and biometric data in real time. This nudges us closer to the vision of precision and personalized medicine, but at the same time, they say we are just scratching the surface of what might be possible.

The industry is clearly at a critical inflection point, says Kevin Hrusovsky, chairman and CEO, Quanterix.

“While we’ve recognized the potential of precision medicine to disrupt healthcare, we’ve yet to fully see the transformation take place,” he says. “With valuation of the precision medicine market estimated to be more than a $141 billion by 2026, there is clearly a strong appetite and while we are indeed close, there is still a lot more we can do. The innovation curve intrinsically depends on our ability to advance technologies that are helping to fuel breakthroughs in this area, from optimizing and accelerating the drug development process to monitoring disease cascades for individual patients to reducing drug toxicity and side effects. Closing the gap between promise and reality will require collective will, but also increased funding, regulatory changes, and a commitment from the scientific and medical community.”