Quick takes: Q&A with Steve Anderson on bringing biomarkers from development to market

Steven Anderson, Ph.D. Chief Scientific Officer, Covance Drug Development

Diagnostics and Drug Development in the Era of Precision Medicine

Steve Anderson, chief scientific officer, Covance, is a welcome speaker at companion diagnostics and precision medicine meetings. He brings to these gatherings his broad-based perspective combined with detailed expertise thanks to his long tenure at Covance and LabCorp.

Steve spoke recently at the Companion Diagnostics Forum in Princeton on the emerging opportunities for precision medicine. He provided his insights on two overlapping areas, demonstrating how precision medicine continues to evolve rapidly as a driver of healthcare. First, he focused on the continuum of biomarker-driven drug development to companion diagnostics applications and validation in clinical trials, a continuum that provides the path for translational medicine successes. He then moved his focus to cell and gene therapy opportunities and challenges regarding applications in precision medicine.

Of equal importance to the long-term view are the near-term issues for delivering precision medicine to patients. Steve touched on factors impacting roll-out and uptake of precision medicine including: advances in identifying biomarkers for safety and efficacy; incorporation of new technologies in laboratories; engagement with agencies for regulatory guidance; value of data for understanding disease biology and natural history leading to improved disease models; and optimization of clinical trial design.

Throughout his talk, he described the opportunity (and perhaps the most subtle benefit) of precision medicine as the seamless translational interweaving of biomarkers, diagnostics, and novel drugs in the development-to-market pipeline. Critical to this opportunity and benefit is the access of companies to large, quality data sets that may lead to introducing new products and capabilities.

As these products and capabilities are validated in the marketplace, we anticipate that healthcare providers will adopt and eventually build their practices around data-informed precision medicine tools.

Steve addressed these topics and more at the Forum. He agreed to follow up with us to address a few questions on related topics:

JPM: Biomarkers have been used for some time to select drug candidates for further development. For example, you noted there are currently over 300 biomarkers in drug labels.

Can you provide examples of Covance’s contributions to this space – either biomarkers or biomarker assays to aid in drug selection?

SA: Covance has a long history of working in the biomarker area across the spectrum of drug development, and because of the breadth of our services have done so in support of both preclinical and clinical development activities. Those studies have ranged from the evaluation of exploratory biomarkers, to the assessment of biomarkers that define mechanism of action of a new therapy, to those that help stratify patients for enrollment in late-stage clinical trials, and when appropriate the incorporation as companion diagnostic. To that end, LabCorp and Covance have supported the development over 60% of the companion diagnostics in use today.

JPM: Has this activity be primarily in-house? or with diagnostics or pharma partners?

SA: We work very closely with our partners, which includes both pharma/biotech companies as well as in vitro diagnostic companies (IVD), who provide tools or assays for use in clinical research studies. Recently, because of the explosion of biomarkers that define disease biology and treatment strategies, our organization has been involved earlier in the process, including the developing of novel biomarker assays.

What were the top 2 or 3 critical lessons learned from this activity?

SA: Managing relationships of all partners through the appropriate governance structure is a key. This enables a comprehensive understanding of the needs, requirements, and timelines of all stakeholders. This structure helps all parties work towards a common goal.

JPM: You spoke about new therapeutic modalities – e.g., gene therapies (replacement, editing, insertion), cell-based therapies (e.g., CAR-T, NK cells). New therapies call for new assays and possibly new modalities.

Can you tell us about work at Covance on identifying biomarkers for development of gene therapies – e.g., safety, efficacy, pharmacokinetic, pharmacodynamic studies, etc?

SA: These are relatively new and rapidly evolving therapeutic modalities, so a number of biomarker assays are being implemented to assess important aspects of the potential efficacy and safety for these novel therapies. Because these therapies involve gene-based modifications of cells or viral vector constructs, the ability to monitor the levels of the engineered materials introduced into the patient become very important as PK/PD biomarkers. Also there are other assays that may help us understand the likelihood of response, such as neutralizing antibodies to the vector (i.e., AAV) used in gene replacement therapy. In addition there are cell-based biomarker assays that may provide insights to potential adverse events related to the novel therapy.

Likewise, can you speak to Covance’s efforts to develop biomarkers for cell-based therapies?

SA: There are a broad spectrum of biomarkers that are being incorporated for use in cell-base therapies such as CAR-T. Measurements of the persistence of engineered T-cells over time, evaluating the level and persistence of the target cell population, monitoring the response of the immune system, measuring the release of cytokines, and evaluating for minimal residual disease are all examples that help the clinician and study sponsors assess how the patient is responding to the treatment.

JPM: Keeping with the cell and gene therapy topic, could you expand on translating these biomarkers and diagnostics to post-development activity in the following areas:

Potential companion diagnostics to identify responders:

SA: While these types of therapy are highly personalized, it is not clear yet the role that companion diagnostics may play. There is the potential for assays to be used to determine which patients should be considered for the therapy, or what the appropriate therapeutic dose might be. Whether these uses meet the specific criteria for consideration as for a companion diagnostic is still an open question. That consideration will be dependent on the positioning of the testing requirements by the biopharma company and the assessment of the need and use of the assay(s) by the regulatory agencies.

Trial design and execution;

There are specific trial design considerations for these studies, as they generally involve very small targeted populations. In gene therapy studies the use of surrogate endpoints that reflect efficacy of the treatment are also important aspects, since for many rare diseases natural history of the disease is not well defined.

In addition, patient engagement to help with recruitment and retention is extremely important, along with understanding the voice of the patient regarding the burden the study participation may place on them. Specific engagements with patient advocacy groups, along with that of the key opinion leaders are also very important considerations for trial design and execution

Manufacturing of cell and gene therapies.

Currently there are a variety of issues regarding the manufacture of cell and gene based therapies. These issues include the use of autologous versus allogeneic materials for gene-modified cell-based therapies such as adoptive T-cell therapies (CAR-T); variation in the vectors used in gene replacement therapies; and the impact of the rapidly evolving use of gene editing. All of these factors are relevant for the current and future trends in manufacturing. Because of variations that exist today in manufacturing processes, and the desire for manufacturing to be near the patient, there is a focus in the industry to standardize and streamline this area. This will enable such therapies more broadly available and to reduce the costs of these therapeutic approaches. Lastly, because of current gaps in manufacturing, the landscape is dynamic. A variety of strategic partnerships or acquisitions have been executed to address current and future needs.

JPM: Adoption and expansion of companion diagnostics applications require addressing commercial factors. You mentioned several, including:

  • Selecting disease areas and Intended use of companion diagnostics;
  • Filing for coverage determination;
  • Added value, impact, patient benefit.

Can you please tell us how Covance goes about developing a consistent strategy to address these factors?

SA: I think you have to start with the end in mind and thereby need to employ a comprehensive approach to all of the key factors for success, ranging from scientific to commercial. The area that has been historically overlooked is commercial delivery. Today many pharma/biotech clients are becoming better at this by involving the commercial teams early in the planning process. In addition many drug developers have added teams with diagnostic development experience so they can interact more effectively with CROs, IVD manufacturers and lab services providers.

Factors related to commercial delivery include understanding patient access, the need for strong payor relationships, a robust reimbursement strategy, as well as considerations for operational delivery such as ease of use, logistics, assay platform and turn-around-time. The ability for clinicians to readily incorporate the testing into their patient management program is also important, but often under-appreciated factor for driving adoption.

JPM: In addition to the technical considerations for commercialization, you also talked about macro-business models in terms of how the therapy and diagnostics would impact a targeted population in one of three ways:

  • Significant portion of a large patient population
  • Relatively small portion of a large patient population
  • Significant portion of a small patient population

Could you please comment on this segmentation strategy? How does the commercialization strategy vary among the different scenarios?

SA: Features such as these drive decisions for testing laboratories such as whether or not to include that specific test in their lab test menu, what platform they use for the testing etc. For example, when does the lab bring up a newly approved companion diagnostic, and, if so, is it a stand-alone test or part of a broader menu of services that addresses the continuum of care for patients. Decisions such as these by testing laboratories potentially impact access and cost for the delivery of these services.

JPM: In your talk, you cited a host of factors impacting the delivery of precision medicine, but I would like to focus on two:

  • Payers / Assessors: Value vs Cost
  • Providers: Better balance between efficacy vs cost

SA: I could imagine making trade-offs on efficacy, cost, and value to achieve an optimal application for a therapeutic application. Can you describe the process at Covance to optimize these trade-offs for a given diagnostic?

Our organization, which has expertise in both providing drug development services as well as diagnostic testing, gives us a unique perspective on the entire lifecycle for the development and implementation of companion diagnostics. We have the ability to develop and implement a companion diagnostic on Day 1 of the drug approval so that it available for patients, providing them with early access to important new medicines. Relationships with the drug developers, payors, biotech companies, IVD manufacturers, clinicians and patients help address the complexity of the process by working with all the key stakeholders to enable timely delivery on the applications for precision medicine. For example, our market access and reimbursement strategy teams work with patients, providers and payors to enable adequate access and coverage for new therapies and the associated diagnostic test. In addition, insights from our real-world laboratory data can help shed light on how companion diagnostics are used to help clinicians make appropriate decisions, and whether there are patient populations or geographies that are underserved and need to be addressed.

A colleague recently reminded me that “those with the data rule the market.” I find that to be (often) true especially in the highly interconnected world of diagnostics, pharmaceutical, and clinical research. LabCorp‑Covance has a unique position of one foot in both the diagnostics and clinical world and strong relations with pharmaceutical companies. What is LabCorp-Covance’s strategy in terms of using these data-rich resources to advance the seamless translation of biomarkers, diagnostics, and novel drugs to patients?

In our company, we have access to a variety of real-world data sets that are relevant to trial design and execution. These data sources include de-identified laboratory-based biomarker data, investigator performance data, and patient insights through our connectivity with patients who may have interest in participating in clinical studies. All of these data sources provide insights into how clinical research is conducted and how commercial strategy helps ensure success for the novel therapy and associated diagnostic assays.

JPM: Thank you for addressing those questions. Any final thoughts to share with our readers?

SA: Precision medicine applications are important today in areas like oncology, and are rapidly evolving to allow for the better delivery of new and novel therapeutic approaches, not only for cancer patients but in other disease areas as well. While multiple stakeholders are actively involved, success depends on a sharp focus on the patients, so that we can deliver new and life‑saving therapies in a timely fashion.

Steven Anderson, Ph.D. Chief Scientific Officer, Covance Drug Development

Steven Anderson is senior vice president and chief scientific officer for Covance Drug Development. He has worked for LabCorp for 30 years and has held a variety of positions, including director of operations for ViroMed Laboratories, director of operations for Monogram Biosciences, director of operations for the Center for Molecular Biology and Pathology, director of operations for Integrated Oncology and Integrated Genetics, national director of research and development, and global head of LabCorp Clinical Trials. His research interests include Molecular Pathology and Oncology based biomarkers, and that work has resulted in the development and validation of multiple companion diagnostics and pharmacogenomic assays in clinical use today.