Companion diagnostics is changing both the way patients are diagnosed and the way they are treated after a diagnosis is made. These kinds of tests have the potential to greatly impact a wide spectrum of disease areas, especially cancer.
Foundation Medical's new test for solid tumors is a prime example of just how impactful companion diagnostics can be. The first FDA-approved test of its kind, FoundationOneCDx, is designed to identify patients who may benefit from treatment with specific targeted therapies, help inform the use of other targeted cancer therapies, provide a tool for doctors to identify opportunities for patients to participate in clinical trials, and help biopharma companies develop new precision drugs. All of that, in one test.
The Cambridge, MA-based company said the test assesses all classes of genomic alterations in 324 genes known to drive cancer growth, providing potentially actionable information to help guide treatment decisions. It is also indicated as a companion diagnostic for patients with certain types of non-small cell lung cancer (NSCLC), melanoma, colorectal cancer, ovarian cancer, or breast cancer to identify patients who may benefit from treatment with one of 17 on-label targeted therapies, including 12 therapies currently approved as first-line treatment for their respective indications. FoundationOne CDx also reports genomic biomarkers that can help inform the use of immunotherapies, genomic alterations in other genes relevant to patient management, and relevant clinical trial information.
According to the company, roughly one in three patients across five common advanced cancers are expected to match with an FDA-approved therapy. The company and its biopharma partners plan to pursue FDA approval for additional companion diagnostics on the platform. The company noted that about 50% of new cancer drugs currently in development are projected to have a companion biomarker.
Along with FDA approval, the Centers for Medicare and Medicaid Services issued a preliminary national coverage determination (NCD) for FoundationOne CDx. The draft NCD would provide coverage for FDA-approved companion diagnostic claims, as well as a pathway for additional coverage with evidence development in other solid tumor types. The final policy is expected to issue during the first quarter of 2018 following public comment of the preliminary NCD and an administrative period.
“Today we know that many people with cancer do not receive biomarker testing, let alone the comprehensive genomic testing they need to be efficiently matched to the best therapeutic option,” said Andrea Ferris, president and CEO of LUNGevity Foundation. “This FDA approval means that, in one test, patients can access therapies where companion diagnostics have been established for their cancer while getting a broad tumor profile that can identify the therapies and clinical trials they could most benefit from. Along with the preliminary national coverage determination, this has the potential to democratize next-generation sequencing, lowering the barriers for patients treated in the community to access these biomarker-driven treatments.”
FoundationOneCDx results are delivered in an integrated report that identifies alterations matched to FDA-approved therapies, identifies additional alterations in genes known to drive cancer growth, furnishes information about genomic biomarkers, provides relevant clinical trial information, and includes interpretive content developed in accordance with professional guidelines in oncology for patients with any solid tumor.
“Comprehensive genomic profiling is the gateway to precision medicine. This decision from the FDA and CMS, which may lead to coverage for Medicare patients, represents an important step forward in improving patient and clinician access to precision medicine – both in setting a new quality standard for this type of testing and offering potentially improved healthcare coverage,” said Ankur Parikh, medical director of precision medicine at Cancer Treatment Centers of America. “Access to important genomic information is a critical step in being able to offer innovative and targeted treatment options.”
Troy Cox, CEO of Foundation Medicine, said the parallel review decision from FDA and CMS represents a major advancement in personalized cancer care. “Beyond its implications for patient care, we expect that FoundationOne CDx will provide biopharma companies with an FDA-approved platform that can help accelerate drug development and enable personalized oncology care."
FoundationOne CDx is the first solid tumor comprehensive genomic profiling test that the agencies reviewed through the Parallel Review program. FDA approval was based on analytic validation and concordance studies with FDA-approved assays, and the company expects the test to be commercially available following finalization of the NCD from CMS.
What’s the key to efficient IVD development?
In the quest to cut costs and optimize operations, healthcare organizations are increasingly turning to business and engineering strategies such as Six Sigma, Lean, and the Toyota Production System. Though each approach differs in method of execution and area of focus, at their basis is the idea of continuous measurement to drive process improvement and standardization for more efficient business operations. These methods can be similarly adopted by the in vitro diagnostics (IVD) industry and incorporated into product development.
IVD development is extraordinarily complex and involves a variety of staff, each with specialized knowledge, working on multidisciplinary teams. Scientific, technical, regulatory, and marketing roles are just a few that can be involved in the development process. Each department (or individual) will be working on their specific contribution to the overall project. This is one reason I recommend a skilled project manager be involved in the process from the beginning so that IVD development moves smoothly.
In the U.S., IVDs and other FDA-regulated products, such as drugs, biologics, and other devices, must be manufactured according to good manufacturing practices and design controls as part of the Federal Food, Drug, and Cosmetic Act (21 CFR part 820). Design controls are not a rigid set of prescribed rules that manufacturers follow. Instead, they are a generic framework that ensures the final product meets users’ needs. Two basic engineering models are used for device development — waterfall and concurrent, but the framework is meant to serve as a model for devices for a wide variety of purposes, so customization is expected.
In the waterfall model, each step is completed before the next one can begin. One consequence of this model is a more protracted development timeline. Delays with individual steps compound over the entire development process, since each step has to be finished prior to the next one beginning. Additionally, each step is somewhat isolated from the others in the overall process, so it is possible that the final product diverges from the initial intent of the designer.
The concurrent model differs from the waterfall method by using a team approach to development. This offers several potential advantages, such as improved communication between groups, reduced production costs and time to product completion because issues that arise can be addressed more quickly. But this model has drawbacks, too, including the potential for components of the product entering the manufacturing phase before they have been adequately validated and verified.
The stage-gate model draws on the best characteristics of the waterfall and concurrent models. At each “stage,” a deliverable that meets specific criteria is required (the “gate”) before continuing the development process. Importantly, the stage-gate model’s phases roughly coincide with design control phases of product development, making it a natural model to use for IVD development. For example, Phase I might entail market analyses, pre-design research, and exploring regulatory strategies. Before moving on to Phase II, when product formulation starts, deliverables such as a solid business plan, market analyses, and reports or white papers on the unmet need, patient care cycle, and clinical workflow would be presented to stakeholders and approved. The stage-gate model is iterative and doesn’t end with the product’s launch. This is an essential part of the continuous measurement/improvement mindset that Six Sigma and other strategies employ. Reassessment of the device throughout the product’s planned lifecycle provides opportunities to address any customer feedback, regulatory and technological changes, and/or market pressures.
Within the crowded IVD landscape, following the stage-gate model as part of design controls can be a competitive advantage. Companies are able to minimize the number of late-stage (read: expensive) changes to product design because they will have been thoroughly vetted by all stakeholders early in the development timeline. Predetermined deliverables keep the process moving along efficiently by serving as a roadmap to production. The end result? A well-designed, thoroughly vetted product that meets users’ needs, any regulatory requirements, and is re-evaluated periodically to adapt to an evolving market—the goal of any IVD developer.
