Inside Track: Precision Partnering

A novel partnership takes aim at developing NGS companion diagnostics in oncology

Interview by Steve Halasey

At the end of July, global reference laboratory leaders LabCorp and Cancer Genetics Inc. (CGI) signed agreements to join the Next-Generation Sequencing (NGS) Companion Diagnostics Center of Excellence program created by Thermo Fisher Scientific, Waltham, Mass. To qualify for participation in the program, laboratory members must demonstrate high-level expertise in oncology testing, maintain a global footprint, and meet the stringent criteria necessary to administer clinical trials for the development and commercialization of companion diagnostics.

As preferred partners, each laboratory will participate in oncology-focused clinical trials in collaboration with pharmaceutical companies and Thermo Fisher. The companies may also qualify for early access to Thermo Fisher’s pipeline of novel platforms and assays to assist with development of Oncomine-branded solutions for clinical and biopharma applications. Upon FDA approval of the tests, members are then well positioned to leverage their experience with the products and be among the first to offer the tests to physicians.

“Thermo Fisher is a highly valued strategic partner to LabCorp, and we are extremely pleased to serve as a center of excellence laboratory for the development of next-generation sequencing-based companion diagnostics,” says David P. King, JD, chairman and CEO of LabCorp. “This partnership, along with the recent opening of our Covance companion diagnostics lab, demonstrates LabCorp’s deep commitment to these important tests, which have the promise of improving the delivery of care based on individualized patient need. Customers of our LabCorp diagnostics and Covance drug development businesses will have access to the innovative technologies made possible through Thermo Fisher’s program.”

In August, CGI will begin offering the Oncomine Dx Target test, the first next-generation sequencing-based test that simultaneously screens tumor samples for multiple biomarkers associated with three FDA-approved therapies for non-small cell lung cancer. LabCorp will begin offering the test later this year. In June, FDA granted premarket approval for the Oncomine Dx Target test, which helps physicians match patients to targeted therapies in days instead of several weeks.

“By partnering with Thermo Fisher to develop and commercially deploy oncology next-generation sequencing panels, we have a unique and early opportunity to bring clinically validated genomic advances into a large-scale clinical setting,” says Panna Sharma, CEO and President of CGI. “Targeted and clinically validated CDx testing gives us the ability to provide our customers with the critical answers they need for their patients in a much faster timeframe, in contrast to the sequential testing approach. As a preferred partner of Thermo Fisher’s center of excellence program, we look forward to bringing more of these valuable CDx testing solutions to market, which ultimately help expedite precision monitoring and therapy selection for cancer patients.”

“Thermo Fisher is committed to expanding its strategic alliances with organizations that share our vision of developing advanced technologies that help doctors get their patients on the right treatment quickly,” says Joydeep Goswami, PhD, MBA, president of clinical next-generation sequencing and oncology for Thermo Fisher Scientific. “This is an important component of our overall strategy to enable precision oncology.”

To find out more about the potential of this partnership, CLP recently spoke with Madhu Ghosh, PhD, senior director of strategic accounts for Thermo Fisher Scientific; Steve Anderson, PhD, chief scientific officer at Covance, LabCorp’s drug development business; and Boaz Kurtis, MD, medical director at CGI.

CLP: What does your organization hope to achieve as part of this program?

Boaz Kurtis, MD: Cancer Genetics Inc (CGI) is a leader in empowering personalized cancer treatment. Our participation in Thermo Fisher’s NGS companion diagnostics center of excellence program demonstrates our commitment to the delivery of precision oncology testing.

Clinicians, pathologists, and others involved in treating cancer patients are increasingly interested in engaging laboratories that are not only certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and accredited by agencies such as the College of American Pathologists (CAP), but also recognized as providing exceptional services by industry partners with a direct stake in the quality of that laboratory’s services. This partnership with Thermo Fisher distinguishes CGI as having that additional level of accountability and trust that many of our referring cancer care providers are seeking.

As a strategic partner, CGI expects to be an early adopter of Thermo Fisher’s NGS companion diagnostics, and to help bring those products to market faster for application in patient care. Through this partnership, we also expect to play a significant role in oncology clinical trials involving FDA-approved NGS companion diagnostics for new treatment regimens.

Steve Anderson, PhD: Thermo Fisher has been a long-standing strategic partner for LabCorp, and it has played a key role in our success at delivering world-class diagnostics to improve health and improve lives. We’re excited about participating in the new center of excellence program, and collaborating with Thermo Fisher on the front lines of developing and commercializing NGS companion diagnostics.

Companion diagnostics are an increasingly important tool to improve the delivery of care by providing the right patient with the right treatment at the right time. And they’re increasingly important to LabCorp. We’ve participated in the development of approximately three-quarters of the companion diagnostics on the market today. And the combined expertise of our LabCorp Diagnostics and Covance Drug Development businesses led us to create a dedicated companion diagnostics lab that recently opened in Morrisville, NC, to support our biopharmaceutical customers in the development of new tests.

Joining Thermo Fisher’s center of excellence program is another extension of our commitment to companion diagnostics, and it will help us to bring more-effective tests and treatments to patients faster.

CLP: More than a hundred potential therapeutics requiring companion diagnostics are now in the pipeline of pharmaceutical companies. Are projects such as these candidates for the NGS-based oncology focus of the center of excellence program?

Madhu Ghosh, PhD: At Thermo Fisher, the center of excellence program represents a concerted effort to work with key opinion leaders, reference centers and hospitals, pharma partners, and practitioners in order to present solutions, results, and opportunities by which companion diagnostic activities for specific oncology drugs and drug combinations can be accelerated down the regulatory path. Our center of excellence partnerships target specific organizations that are not only global leaders in clinical testing—in this case for non-small cell lung cancer solid tumor samples—but also have long-term relationships with pharma companies.

CLP: Do all or most of the center’s projects have a pharma company connection?

Ghosh: Yes. Our center of excellence partnerships focus on our pharma relationships as well as on collaborative activities that enable the center and its members to participate in such discussions. The center is truly a win-win-win situation for every party involved, as it enables us to accelerate development timelines and ultimately reduce the time to patient care.

CLP: To what extent will the laboratory partners be involved in the actual development of new tests?

Ghosh: Thermo Fisher collaborates with its center of excellence partners in many different ways. We’re proud to have some of industry’s most-respected scientists and leaders in software and bioinformatics among the center’s R&D teams. The pipeline for oncology diagnostics is very exciting and promising, and input from Thermo Fisher R&D is playing a significant role in keeping it full and flowing. Through the center and its members, we’re able to take into account voice of customer and key opinion leader input even before participation is requested for analytical or clinical validation activities leading to regulatory submission of a companion diagnostic.

CLP: Diagnostic applications of NGS are still very new to clinicians and laboratorians—and to payors. How much will the lab partners be engaged in refining test protocols or defining the health economic parameters of proposed new tests?

Anderson: LabCorp has a long history of participating in the development of new testing technologies and leading their commercialization, from being the first to commercialize polymerase chain reaction (PCR) to participating in the development of more than three-quarters of the companion diagnostics on the market today. We have helped introduce many new tests based on NGS technology, and we have significant expertise in working with companies like Thermo Fisher, biopharmaceutical clients, regulators, clinicians, and payors to address the full range of issues related to the development and introduction of new technologies.

We will continue to focus on promoting NGS for patient care where appropriate. For example, NGS shows particular promise for patients who are only able to provide a small tissue sample, and for whom we need to deliver a very sensitive, comprehensive analysis that provides the treating physician the most actionable information possible. We will continue to work with clinicians and payors to educate them about the utility of these approaches.

CLP: What do you see as the key challenges involved in bringing NGS-based companion diagnostics to market?

Ghosh: The key challenges currently affecting these efforts are mostly the obvious ones: the cost of NGS companion diagnostic development, pharma drug-approval timelines, and time-to-market challenges in a competitive marketplace. We work closely with our pharma partners to ensure that the regulatory submissions for an investigational new drug and its companion diagnostic are aligned. The biggest challenge is managing the alliances among the pharma team, the Thermo Fisher program team, members of the center of excellence, and any contract research organizations assisting in development of the companion diagnostic. Ultimately, we all have to remember that our goal is to ensure that we can submit high-quality companion diagnostics for premarket review, and do so on time.

Anderson: Aside from those general challenges involved in developing new testing technologies, the main challenges specific to NGS companion diagnostics lie in educating physicians and payors about the benefits of the technology, to help make the tests more readily available to the patients who need them.

Kurtis: Healthcare providers and physicians have historically been slow to adopt new technologies for direct patient care. Consequently, physician education and demonstrations of clinical utility will undoubtedly be critical for achieving market acceptance of NGS companion diagnostics. Fortunately, NGS is now reaching the point at which the analytical and clinical validity of the technology have been widely documented, and the results of clinical studies are gradually demonstrating the advantages of its use in clinical applications.

However, it will take more time for the market to establish price points for NGS testing that make it easier for a large number of laboratories to adopt the technology, so that more patients can benefit from its use. The specialized nature and premium pricing of the equipment and reagents needed for NGS testing could pose a challenge to wider acceptance. The current reimbursement landscape may also be a deterrent to broader market adoption of NGS companion diagnostics, so changes to reimbursement policies may also be needed.

CLP: The design of clinical trial strategies can have important ramifications for the labeling and use of a new therapy. How does this consideration influence the way the partners operate?

Anderson: In the design and execution of clinical trials, drug developers are increasingly focused on the use of biomarkers, which may range from exploratory biomarkers to those used to stratify patients for a drug trial. There is also continually increasing interest in the use of multiplexed genomic biomarkers.

NGS allows for the assessment of appropriate panels of biomarkers relevant to the study of a novel drug candidate. In oncology, because tissue availability is critical, having a platform that maximizes the use of tissue samples to interrogate higher biomarker content is extremely important when executing a clinical trial.

CLP: FDA recently approved the Thermo’s Oncomine Dx Target test, which screens tumor samples for multiple biomarkers. Is such a multiplexed approach a common goal of the center’s efforts?

Ghosh: Yes, that is precisely the direction we think targeted oncology diagnostics are heading. Thermo Fisher is at the forefront, with its FDA-approved Oncomine Dx Target test accompanying Iressa (Astra Zeneca), Mekinist and Tafinlar  (Novartis), and Xalkori (Pfizer). We are working with many cutting-edge pharmaceutical companies that are taking a similar multiplexed approach to their drug’s companion diagnostics programs.

The key opinion leaders associated with our center of excellence program are keen to be aligned not only with Thermo Fisher, as a diagnostic instrument manufacturer, but also with our partner pharmaceutical companies and their goals for patient care. A multiplexed approach is the obvious method for continuing to push the boundaries for companion diagnostics as well as for state-of-the-art pharma drug trials.

CLP: How does the center’s coordinated approach to development and clinical testing facilitate regulatory approval of novel companion diagnostics?

Ghosh: Our program teams work closely with members of the center of excellence, not only training them on how to perform clinical tests, but also guiding them toward the validation of their assays, as needed. The center of excellence and its research arms assist in reproducibility and validation activities that support significant parts of regulatory submissions for both drugs and diagnostics. The center contributes tremendously toward reducing timelines, gathering voice-of-customer input, and generating data that can be included in novel companion diagnostics submissions, as was the case with the Oncomine Dx Target test.

Anderson: LabCorp utilizes the three-way partnerships among pharma companies, IVD manufacturers, and laboratories to provide both the analytical and clinical data necessary for the success of both the therapy and diagnostic. In addition, through our dedicated companion diagnostics laboratory, we have the ability to develop novel applications on different testing platforms, and to support the regulatory submission for a diagnostic application linked to a specific therapy.

Kurtis: CGI’s expertise in using research partnerships to bring novel diagnostic tests to market is a key resource that can help to facilitate faster approval of new diagnostics. Every companion diagnostic project that CGI works on is assigned a project manager who coordinates all aspects of the partnership with the biopharma company and the assay manufacturer, and oversees the clinical testing that we do internally. If necessary, we will send one of our pathologists offsite to be trained on the analysis and interpretation of a particular assay. We test as many specimens as needed to provide the quality of data that our partners need to take the diagnostic through the regulatory approval process, which we understand can be a tricky road to navigate.

CLP: As a business model, does participation in the center help to diversify the risks involved in developing complex oncology tests? What other benefits does participation offer?

Anderson: We view participation in the center of excellence program as a way to combine expertise across the full spectrum of resources needed to bring companion diagnostics to market faster and encourage their adoption by both clinicians and payors. Diversification or mitigation of risk is not a primary motive for our participation in the program.

Kurtis: Participation in Thermo Fisher’s center of excellence program provides CGI early access to innovative tests that complement CGI’s mission to be a bench-to-beside partner for guiding oncologists who are making therapeutic and disease management decisions for their patients.

While we don’t necessarily look at participating in the center of excellence program as being part of a business model, the program does provide us with an opportunity to position ourselves with pharmaceutical companies as a quality partner for execution of their oncology trials.

We see the center of excellence program as being about good laboratory practice; consequently we expect that our approach to diagnostics will remain the same. We certainly want people in the oncology community to know that we are participating in the program, but whatever benefits result from that participation is for the community to decide.

CLP: Do you think focused partnerships such as those of this center are likely to become a preferred model for the development of diagnostic tests using novel technologies?

Ghosh: We certainly hope so. When a complex project such as the Oncomine Dx Target test reaches its submission phase as a companion diagnostic, it is important to acknowledge the many pharma collaborators and multiple contract research organizations that contributed to the final 220,000-page submission to FDA. That project has been a tremendous success, so it’s natural that we would want to replicate it, with the ultimate goal of improving patient care and medical intervention through companion diagnostics.

Kurtis: Yes, CGI strongly believes that focused partnerships are already essential for bringing novel diagnostic technologies to market. In the diagnostics sector, focused partnerships enable a number of companies to combine their expertise in order to accelerate the development of key technologies that may ultimately guide physicians to make better-informed patient management decisions. With the advent of targeted therapies comes the need for targeted testing, which can be achieved with vastly increased throughput and accuracy using NGS technology.

CGI has extensive experience with NGS—as both a clinical diagnostic tool and as a research and exploration platform—and we can confidently partner with any company looking to develop or commercially launch a new test using this technology. The numerous partnerships we have maintained over time are a testament to the quality of our work.

Anderson: This center of excellence partnership represents an exciting opportunity to collaborate with an established strategic partner. While we don’t necessarily believe that formal partnerships will become the preferred model for the development of new testing technologies, partnerships such as these are a powerful way to enhance our abilities and increase the speed with which we launch new tests that make use of novel technologies. They leverage the specific strengths of each organization to help patients and address specific clinical needs. This model fits well with our goal of working with our pharma and IVD manufacturing partners to get new drugs and companion diagnostics to market faster.

Thermo Fisher’s program reflects an increasing awareness of the need for greater collaboration in developing new healthcare approaches, and it’s a great example of how that can be achieved in a thoughtful, intentional way. As a leader in medical testing and contract research, LabCorp has always valued the strategic partnerships built across the industry over the years. Participation in the center of excellence program is an extension of our collaborative approach to business.

In the end, all of our efforts are about bringing more-effective tests to market, and helping patients get on the right treatment more quickly. We see the center of excellence partnership as an effective way of achieving these goals, and we look forward to exploring more options to work with Thermo Fisher on new tests and new applications for existing tests.

Steve Halasey is chief editor of CLP.