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Progress in Companion Diagnostic Development for Low-Grade Glioma

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The development of companion diagnostics is helping clinicians to match patients more promptly to the right therapy, which can greatly improve the chances of successful patient outcomes, as well as reduce the risks of negative treatment effects.

As part of its efforts in this space, Thermo Fisher Scientific has expanded its partnership with Agios Pharmaceuticals to co-develop a companion diagnostic for vorasidenib, an investigational treatment for IDH mutant low-grade glioma. Breakthrough Device Designation was recently granted by the FDA to the Oncomine Precision Assay to identify IDH1 and IDH2 mutations in low-grade glioma patients. The assay runs on the Ion Torrent Genexus System, which can deliver comprehensive genomic profiling results in a day.

To learn more about these developments, the benefits of accelerating turnaround times for genomic testing, and the importance of partnering with pharma companies to develop companion diagnostics, Technology Networks spoke with Luca Quagliata, PhD, BCMAS, Global Director of Medical Affairs for Thermo Fisher Scientific.

Anna MacDonald (AM): Can you tell us more about the FDA Breakthrough Device Designation and its significance?

Luca Quagliata (LQ): The goal of the FDA’s Breakthrough Device Program is to provide patients and health care providers with timely access to medical devices that help fill a gap for unmet medical needs by providing effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases. In compliance with the program’s stringent criteria, the FDA recently granted Breakthrough Device Designation to Thermo Fisher Scientific’s Oncomine Precision Assay to identify low-grade glioma (LGG) patients with isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations who may be eligible for vorasidenib (AG-881). The assay is designed to run on Thermo Fisher’s Ion Torrent Genexus System, which is the first fully automated next-generation sequencing (NGS) platform with a specimen-to-report workflow that delivers comprehensive genomic profiling results in a single day. Over time,Thermo Fisher seeks to receive premarket approval for the Oncomine Precision Assay as a companion diagnostic for multiple therapies, as well as approval for liquid biopsy tumor profiling in lung cancer and solid tissue tumor profiling in multiple cancer types. As the FDA’s Breakthrough Device Designation is typically reserved for game-changing tools, the designation represents a big step forward in Thermo Fisher’s endeavor to ensure that more clinicians can have quicker access to comprehensive genomic information and match patients with the right therapy more efficiently.

AM: What is a companion diagnostic, and what are some of their main benefits?

A companion diagnostic (CDx) is a medical device that enables clinicians to identify patients who are more likely to benefit from a given therapy. The results generated via a companion diagnostic test allow physicians to prescribe specific drugs (in label drug use), reassuring the best possible therapy match for the patient. More precisely, the primary goal of the companion diagnostic-based approach is to match the right patient with the right therapy, thus minimizing the possibility of non-effective treatments, and weigh potential risks and side effects against tangible clinical benefits. One example of a CDx is the Oncomine Dx Target Test, the first next-generation sequencing (NGS) in vitro diagnostic approved by the FDA as a CDx for non-small cell lung cancer (NSCLC). It is able to test for 46 cancer-related biomarkers all at once and with the lowest input sample requirements on the market, enabling certified laboratories to generate a comprehensive genomic profile of a patient’s tumor within a few days. The Oncomine Dx Target Test provides the clinical care team with the information needed to match the patient to the right treatment, with the goal of improving patient outcomes. 

Since receiving premarket approval for the Oncomine Dx Target Test in 2017, Thermo Fisher has accelerated its work to expand the use of comprehensive biomarker testing globally. Most recently, Thermo Fisher announced its partnerships with Daiichi Sankyo and Chugai Pharmaceutical to co-develop a companion diagnostic using the Oncomine Dx Target Test to identify NSCLC patients who may be eligible for their targeted therapies.  

AM: Thermo Fisher Scientific has extended its partnership with Agios Pharmaceuticals to co-develop a companion diagnostic for vorasidenib. Why are such partnerships with pharma companies so important during the development of a companion diagnostic?

Developing a new drug is an extremely complex process that requires an extensive amount of investment and energy. However, generating an effective drug is only one part of the journey to reaching the patient. The development of a companion diagnostic is a critical element to improving patient outcomes. To that end, Thermo Fisher is working closely with global pharmaceutical partners to develop companion diagnostics for many of the targeted therapies available to patients today and in the future. In fact, the vast majority of the latest targeted therapies approved by the FDA received clearance along with a defined companion diagnostic test. We foresee CDx activities as yet another fundamental driver of our future business expansion within the molecular profiling market, particularly as we continue our commitment to work with pharmaceutical partners to identify more patients who may benefit from the latest targeted therapies.

AM: The Ion Torrent Genexus System can deliver comprehensive genomic profiling results in a single day. How does this compare to current turnaround times? What are the advantages of accelerating turnaround time for genomic testing? 

Currently, it can take up to four weeks for oncologists to receive outsourced NGS test results, while in-house-generated test outcomes are typically available for most NGS accredited centers within 10 business days. The Ion Torrent Genexus System features a fully automated specimen-to-report workflow that shortens the turnaround time down to a single day, meaning clinicians and patients may have access to timely, comprehensive test results, guiding targeted therapy when the system is eventually approved. This access to quick and accurate molecular profiling is critical, particularly nowadays where the pivotal importance of PD-L1 IHC as a biomarker for the selection of first-line immune checkpoint inhibitor treatment for multiple indications is challenged by the lack of response in a substantial number of treated patients.

Another advantage of accelerated turnaround time for genomic testing is the ability to quickly match patients with oncology clinical trials, which is an otherwise complex process. For example, Thermo Fisher recently partnered with Q2 solutions to use the Ion Torrent Genexus System to reduce the time to deliver clinical reports to trial sites, enabling patients’ access to investigational drugs faster. Lastly, there is an emotional advantage of accelerated turnaround time to consider, as patients and their families understandably experience an immense amount of stress and anxiety when they need to wait for test results. The ability to receive test results faster and be able to make rapid treatment decisions is an important benefit to both patients and clinicians.

AM: Why is it beneficial to use comprehensive NGS testing over single-gene testing?

Up until recently, many clinical laboratories considered comprehensive molecular profiling via NGS to be too costly or complex to be handled in-house. As a result, these laboratories have relied on single-gene testing, which typically offer limited information. When single-gene tests are applied sequentially, it can delay the time it takes to receive a comprehensive genomic profile of a patient’s tumor. As a direct consequence, patients must wait longer before they are placed on an appropriate treatment regimen. In contrast, targeted NGS panel testing enables clinicians to obtain a comprehensive picture of a patient’s genomic profile with just one test so the clinical care team can make a more informed therapy selection from the very beginning.

 With the availability of cost-effective, simple-to-use NGS solutions, such as the Ion Torrent Genexus System, many hospitals and government healthcare agencies are now considering the benefits of in-house NGS testing. This shift, aiming to reduce the critical time between testing and treating, is a major step forward to realize the promise of precision medicine and, ultimately, provide better outcomes for patients in the future.

AM: The Ion Torrent Genexus System can be used in several applications outside of oncology. Can you tell us a little about how it has been used to support SARS-CoV-2 studies?

As countries begin to reopen, there is a critical need for real-time SARS-CoV-2 sequencing data that can be quickly and easily generated and used to inform potential intervention strategies that may help limit the impact of the COVID-19 crisis. To support this need, Thermo Fisher recently introduced the Ion AmpliSeq SARS-CoV-2 Research Panel for the Ion Torrent Genexus System, which provides laboratories with a powerful workflow to carry out infectious disease studies using minimal amounts of sample. The rapid turnaround time of a single day and the automation that the Genexus System delivers can accelerate researchers' understanding of how the virus is evolving, assist with contact tracing and transmission interruption efforts, and inform vaccine development programs—all of which are critical containment strategies that are essential for preventing or reducing the chance of SARS-CoV-2 resurgence.

As an example, in March 2020,
two teams of infectious disease researchers in Italy used the Ion AmpliSeq SARS-COV-2 Research Panel to further analyze the SARS-CoV-2 genome from samples acquired locally. The teams sequenced multiple samples and generated early data suggesting the virus's genome is stable. The findings increase the likelihood that future coronavirus vaccines can have a higher rate of effectiveness and could help the global scientific community’s effort to better understand the epidemiology and spread of COVID-19.

Luca Quagliata, PhD, BCMAS, Global Director of Medical Affairs for Thermo Fisher Scientific, was speaking to Anna MacDonald, Science Writer for Technology Networks.