Proceedings: DIA 2019 Global Annual Meeting

DIA GAM 2019
Understanding and Overcoming Barriers to Adoption for Precision Medicine

Kayla Valdes


recision medicine (PM) is founded on the principle that therapeutic intervention can no longer be a “one-size-fits-all” approach if it is going to be optimally effective for each patient. A myriad of genetic and environmental factors need to be taken into account in order to develop an appropriate and effective treatment plan for patients. Major drug classes are prescribed by trial-and-error; however, PM aims to develop targeted therapies specific to the individual patient to increase the likelihood of success. Additionally, PM has the potential to reduce adverse drug reactions and the use of invasive testing procedures, while improving patient adherence to treatment, thus decreasing the overall cost of healthcare.

Speakers at the Precision Medicines in Clinical Trials: Understanding and Overcoming Barriers to Adoption session examined the latest challenges and opportunities impacting precision medicine in the pharmaceutical and biotech industry today.

Key Takeaways

  • Through the development of molecular and genetic diagnostic tools, PM can use predictive biomarkers to better match patients with a targeted therapy.
  • Precision medicine has flourished in cancer therapy, and new immuno-oncology treatments, such as checkpoint inhibitors or CAR-T cells, are the latest types of individualized therapies specifically designed to treat tumors based on genetics rather than tissue of origin.
  • Innovative trial designs such as umbrella trials, basket trials, and master protocols are key to the progress of PM; however, these trials have a low adoption rate due to negative perceptions within pharma due to a lack of regulatory harmonization.
PM is a rapidly evolving field in which healthcare providers use molecular diagnostic tools in combination with an individual patient’s medical history to develop a personalized and targeted treatment approach for any given disease. Proactive and preventative, PM is a new paradigm in healthcare that is expected to impact all aspects of drug development and enhance patient care. In order to fully realize PM’s disruptive potential, a multipronged strategy that revolutionizes the healthcare ecosystem through scientific, clinical, and policy changes must be employed.

Since the sequencing of the human genome over 15 years ago, the biopharmaceutical industry has increasingly invested in developing individualized therapies. The majority of trials for such drugs are conducted in the United States, followed by the European Union. In 2018 alone, the FDA approved 25 new “precision medicines” (42 percent of all approved new molecular entities), with the majority having an indication in oncology or single-gene disorders.

The Promise of Precision Medicine in Immuno-Oncology

As the understanding of individual genetic risk factors for cancer, identification of predictive biomarkers, and the adoption of tumor profiling techniques grows, PM is increasingly becoming a viable treatment strategy in oncology. In 2017, the landmark FDA approval of Merck’s Keytruda, a checkpoint inhibitor, represented an important first for the field of PM. This immuno-oncology drug is used to treat cancers based on a particular biomarker, and not on the tumor’s location in the body. Molecular analysis of the patient’s tumor by a companion FDA-approved test dictates whether the patient is a candidate for this treatment.

Chimeric Antigen Receptor (CAR) T-cell therapies are also used in precision oncology. To date, FDA has approved two CAR-T cell therapies, Yescarta and Kymriah, for selected cancers – certain types of lymphoma and leukemia, respectively. CAR-T cells therapies use engineered T cells from the patient (autologous) or healthy donor (allogenic) that identify cancer cell-specific signals that target and destroy tumors on a patient-by-patient basis, making this therapy a truly individualized treatment option in oncology.

Innovations in Clinical Trial Design in the Era of Precision Medicine

Traditional randomized clinical trials (RCTs) compare the average responses between treatment arms to determine efficacy. RCTs are not conducive to PM, where interventions are chosen on an individual basis using a patient’s genetic or molecular profile. With oncology moving towards a tailored, biomarker-driven approach and single-gene disorders being another prime target for PM, there is a need for alternatives to the traditional RCT. Industry and academics have developed innovative clinical trial designs, such as basket or umbrella trials or the use of master protocols, not only to allow for measuring responses in small subgroups of patients, but also to allow for a decrease in cost and an increase in efficiency in the development of PMs.

With these new trial modalities, novel therapies, such as immuno-oncology drugs, can be tested in the appropriately genetically-matched patient population. Specifically, tumors can be placed in the same “basket” or “umbrella” based on common molecular or genetic properties rather than tumor tissue of origin. In general, recruitment for these innovative trial designs is much less cumbersome, due to the smaller number of patients needed and the ability to test a broader range of drug candidates or genetic backgrounds.


Anita Nelsen, Vice President, Translational Medicine, Parexel (Chair)

Yeul Hong Kim, Professor, Section of Medical Oncology, Dept. of Internal Medicine, Korea University Anam Hospital

Edward Abrahams, President, Personalized Medicine Coalition

Rebecca Blanchard, Vice President, Translational Pharmacology, CRISPR Therapeutics

Moving Towards Precision Medicine: The Challenges Ahead

Alignment across the research, regulatory, and reimbursement environments is crucial to promote the development of PM. There is a need for parallel drug and device development programs that can help match the appropriate diagnostic with the appropriate drug as well as better standardization of diagnostic tests. However, the benefits of PM are apparent in cancer treatment with the discovery of predictive biomarkers and concomitant development of immuno-oncology therapeutics.

While it is apparent that innovative clinical trials go hand-in-hand with PM, there is a lack of global regulatory harmonization for such trials. Both the FDA and the EMA are working towards driving the adoption of these trials, which will presumably allow faster approvals. Additionally, ICH is working on establishing harmonization criteria for innovative trial designs in order to overcome this issue. Academics and industry alike continue to explore new ways to improve the drug development process through the adoption of innovative trial designs in order to match novel treatments to specific patients more quickly.

PM holds promise for revolutionizing many aspects of drug development, the health of patients, and the healthcare system. Challenges remain including regulatory hurdles for individualized therapies and difficulty in coverage and reimbursement of these therapies. Also, physicians are slow to incorporate new routines into their clinical guidelines without evidence of the value of any given technology or treatment. As the relationship between patients and physicians continues to evolve, and patient engagement becomes more prevalent in drug development, the shift towards PM is expected to continue.