One may fail when one simply lacks the resources to succeed. That’s painful enough. But how much more painful is it to fail when one does have the resources, but deploys them poorly? That greater pain is something that the leaders of precision medicine mean to avoid. Many of these leaders met at the 16th Annual Precision Health Conference, which was held last May in San Diego. There they participated in “a cross-sector exchange of perspectives on the scientific, business, and policy issues influencing the status and outlook for personalized medicine.”
At this event, many presenters emphasized the need for coordination. Precision medicine, they agreed, would struggle to succeed if its greatest assets were to languish in isolation. What use, they asked, is diagnostic acumen if panel tests are less than comprehensive? What use are genomically identified targets if they remain unexplored? What use are cell-based therapies if patients who could benefit are not screened or informed of their options in systematic ways? What good are data sets that are scattered rather than unified and capable of presenting 360-degree views of each patient’s health information?
To revisit these questions, GEN spoke with several Precision Health Conference presenters. They share their insights here. Besides describing how precision medicine is making better use of its resources, they point to applications that will soon be within reach, including applications beyond cancer.
Personalizing cancer screening
At Exact Sciences, a molecular diagnostics company that provides a comprehensive suite of cancer tests, the leadership is optimistic about the prospects for personalized care, particularly with respect to the prevention of disease. “Prevention is our greatest tool in the fight against cancer,” says Kevin Conroy, Exact’s chairman and CEO. “Cardiovascular mortality has decreased 70% in the last 50 years by focusing on prevention. We can achieve similar results for cancer.”
Progress, Conroy adds, depends on the development of appropriate screening technologies. “Cancer screening should be planned, programmatic, and personalized,” he insists. “One in two men and one in three women will develop cancer in their lifetimes, yet today 70% of incident cancers have no screening methods. Eradicating cancer will require a widely available, comprehensive platform of tests and treatments for patients.”
Conroy highlights five areas and details what each needs to accomplish:
- Hereditary cancer assessments should arm people with the knowledge of their personal risk of cancer.
- Screening tests should facilitate earlier detection of many more types of cancer, including rare cancers.
- Therapy guidance tests should help patients and healthcare providers select the right course of treatment and avoid overtreatment and undertreatment.
- Minimal residual disease tests should assess whether treatments eliminate cancer, and monitor for recurrence on a personalized basis.
- Electronic medical record integration and digital tools should become simpler and automate the impact of personalized medicine.
“We applaud others who share in our mission,” Conroy declares. “It will take more people and organizations getting involved to ensure the best ideas are combined to yield new, extraordinary results.”
Targeting the kinase tree
More than a decade ago, Blueprint Medicines was launched as a developer of personalized medicines. Since then, Blueprint has centered its discovery efforts around the 518 kinases encoded by the human kinome.
For most of these kinases, functions remain unclear. However, by studying these kinases, the company expects to identify kinase variants that drive the growth of varied cancers.
“Kinase medicines are designed to block the activity of protein kinases—enzymes that regulate critical biochemical pathways in cell growth, survival, metabolism, and immune activity,” explains Kate Haviland, Blueprint’s president and CEO. “However, early-generation kinase medicines were limited by poor selectivity, off-target effects, and the emergence of resistance.
“The challenge, historically, has been that toxicity is driven by both activity against the wild-type protein as well as off-target activity on other tyrosine kinases. But we’ve been able to make molecules that are highly selective and combinable, and I think this is really the beginning of a new journey.”
Haviland indicates that Blueprint has developed a proprietary scientific platform that allows the company to rapidly and reproducibly design medicines that selectively target kinase drivers of disease, enabling improved potency, less off-target activity, and an increased probability of clinical success. She remarks, “We believe we are the only biotechnology company to discover two novel programs and advance them both into the clinic and through multiple regulatory approvals in less than 10 years.”
Blueprint has two commercially approved products. The first product is avapritinib. (In the United States, the trade name is Ayvakit; in Europe, it is Ayvakyt.) Avapritinib gained FDA approval for patients with advanced systemic mastocytosis in June 2021, and it gained European Commission approval in April 2022. The product is also approved for a genomically defined subset of patients with gastrointestinal stromal tumors. The second product is pralsetinib (trade name: Gavreto). Pralsetinib is approved for patients who have metastatic or advanced RET-altered cancers, such as non-small cell lung cancer or medullary thyroid cancer.
Closing the “practice gap”
Sometimes patients whose cancers test positive for specific biomarkers never receive available targeted treatments that could have helped them. This “practice gap” can result from a number of causes.
“While personalized medicine presents many new and more effective treatment options for cancer patients, biomarker testing and targeted therapeutics are still relatively new in oncology,” reveals Susanne Munksted, chief precision officer, Diaceutics. “Stakeholders are facing multiple challenges in adapting their cancer care practices and pathways to effectively implement and deliver precision oncology to patients.”
These challenges, Munksted notes, include a clinical “practice gap” between the availability and the applicability of multigene panel tests. Indeed, many patients who have actionable mutations do not receive targeted therapies. (According to a recent paper in Clinical Lung Cancer (2020; 21: P477–P481), the gap is attributable, in part, to “limitations in the availability and interpretation of next-generation sequencing results, sample processing constraints, limited access to targeted therapies, and lagging awareness of the rapidly evolving field of personalized medicine, all of which result in ‘clinical inertia.’”)
“Other issues include a high variability in the levels of biomarker testing and appropriate treatment decisions across different practice settings, tumor types, and biomarkers,” Munksted continues. “There is also varying adherence to testing guidelines. Another complication is that it takes on average 4.5 years for a diagnostic assay to be available and adopted to test the biomarker-positive patient population. This complication delays patient treatment.”
Diaceutics is working to solve these challenges: “We are committed to securing improved treatment by enabling better testing for patients globally,” Munksted relates. “We are conducting work in collaboration with the Personalized Medicine Coalition to enhance our understanding of the impact associated with the clinical practice gaps on the patient care journey.”
Diaceutics has established DXRX, a diagnostics network-enabled platform that provides access to global diagnostic testing data from an international network of laboratories and offers a novel approach to diagnostic development and commercialization. Munksted says the goal is to provide unrivaled access to comprehensive data analytics and to ensure that “every patient [receives] the treatment they deserve.”
Realizing the promise of cell-based therapies
In 2017, the first chimeric antigen receptor (CAR) T-cell therapy was approved for patients with acute lymphoblastic leukemia. Ever since, CAR T-cell therapies have promised to deliver breakthroughs in the fight against cancer. But these breakthroughs have yet to be seen. Why? According to Christi Shaw, the CEO of Kite Pharma, the traditional anticancer approach—high-dose chemotherapy followed by stem cell transplantation—continues to be followed by physicians responsible for treating patients with progressive disease.
“Innovative therapies matter only if they reach patients,” Shaw asserts. “Not enough eligible patients are aware of and/or are being referred to CAR T-cell therapy. … That’s why we are working closely with advocacy groups to help inform patients and their care partners of different treatment options available to them and how to advocate for themselves throughout their treatment journey.”
Shaw says that Kite works with 275-plus authorized treatment centers around the world where patients can receive CAR T-cell therapy. “These hospitals,” she adds, “need to have great working relationships with community oncologists in order for patients to receive timely care and smoothly transfer back to their community oncologist for follow-up.”
According to Shaw, a fast and dependable turnaround time also is critical. “We are proud of our rapid and reliable 96% manufacturing success rate,” she declares. “In the United States, for example, we get the patients’ individually made therapies back to them in about 16 days.”
The company has two FDA-approved CAR T-cell therapies in five indications, and it is already building on these accomplishments. “We are continuing to explore how we can bring innovative cell therapies to patients in other forms of blood cancer and [do so] earlier in their treatment journeys,” Shaw elaborates. “With every piece of new research, and every piece of real-world evidence where we see patients benefiting, we inch closer to accomplishing our goal of changing the way that cancers, and potentially other diseases, are treated through personalized cell therapy.”
Taking on CNS disorders
Personalized medicine is best known for its oncological applications, but it has applications in other areas, too. One of these areas is neurology. “Applications in neurology are unfolding and attracting investment,” reports William Hagstrom, the founder and CEO of Octave Bioscience. “Neurodegenerative diseases like multiple sclerosis (MS), amyotrophic lateral sclerosis, Huntington’s, Parkinson’s, Alzheimer’s, and more are not only incredibly heterogeneous diseases that affect many, but are also costly with generally poor outcomes. These diseases currently are measured subjectively, leaving a need for precision care solutions that look at them objectively.”
“To improve outcomes, we need to improve disease management, which is powered by improved objective measurement,” Hagstrom notes. “That requires an overhaul of the methods by which we measure the biology of MS and how it manifests itself in a particular patient’s symptoms.”
Octave is currently focusing on MS, but the company plans to address the full spectrum of neurodegenerative diseases. To do so, the company intends to leverage its multidimensional approach. “We have a finely choreographed and integrated model,” Hagstrom explains. “Our comprehensive solution includes a first-of-its-kind multivariate biomarker blood test; enhanced MRI analytics; imaging insights and protocols; and a clinical program [in which] wearables and mobile tools [enhance monitoring]. Together, these create an unparalleled, longitudinal view of a patient’s disease to support patient and physician clinical decisions.”
“This model for precise care for MS holds great promise,” Hagstrom continues. “The platform we are constructing will be applicable to other neurodegenerative diseases, and we anticipate seeing more and more cases for our multidimensional model, which employs cutting-edge science and technologies combined with data analytics to serve individual patients and entire populations.”
Embracing a data-driven future
“Data is critical to unlocking the promise of precision health and personalized medicine,” declares Amy P. Abernethy, MD, PhD, president, Clinical Studies Platforms, Verily Life Sciences. She adds that if data is to play its key role, it will have to be comprehensive and provide a 360-degree view of health.
In other words, many kinds of data are needed. They include prospectively collected data (such as data from clinical trials), passively collected data (such as data from electronic health records), and other data sets (such as genomic, microbiomic, and other biologic data). “A comprehensive view,” Abernethy continues, “also includes data from social determinants of health, environmental exposures, and concerns for quality of life.”
Besides noting that precision medicine needs to gather different kinds of data, Abernethy points out that precision medicine needs to accumulate data over time. “Traditionally, the focus has been on one research question, one data set,” she explains. “I see a big shift as we work to build data sets that combine what is already available in the ecosystem plus data that has been newly created. Such data sets can be used to answer many research questions, not just one, generating the evidence needed to make precision health a reality.”
Abernethy asserts that Verily is committed to bringing “precision health to everyone, every day.” She describes the company’s approach as follows: “We are working to leverage software and digital tools in a practical way to make the process more efficient by pulling the data streams together and assembling data sets. However, since not all challenges will be solved by software, we are also relying on user experience and user design so that we can build solutions that are as patient focused and as efficient as possible for all of the actors in the healthcare ecosystem.
“We are also very focused on building technology and tools that incorporate all available data to address the challenges of data quality and longitudinality. We feel that these will be the solutions of tomorrow.”protein cell-based