The Blueprint for Drug/Diagnostic Co-Development

Earlier today, Friends of Cancer Research and Alexandria Center for Life Sciences hosted their third-annual Blueprint for Drug/Diagnostic Co-development forum. Panelists at the forum, which included Foundation Medicine and the FDA, among others, discussed new paradigms for the regulation, standardization, and reimbursement of next-generation sequencing (NGS) tools and assays (see HERE for the session’s agenda).

In conjunction with the forum, an NGS Working Group, comprised of representatives from the academic, drug development, and government sectors, and including Foundation Medicine, led the drafting of a white paper titled “A Blueprint for Drug/Diagnostic Co-Development: Next-Generation Sequencing (NGS) in Oncology” which was circulated and discussed at the forum. Key highlights from the white paper are summarized below:

  • Emphasis on the need for a process that allows flexibility in FDA review so an assay can be amended via an expedited review process to allow for the incorporation of new markers: “FDA-cleared panels may quickly become obsolete based on the rapid evolution and discovery in the oncology field. Identifying a mechanism for ensuring rapid inclusion of new markers, performance data for genomic alterations, and updates to assay performance are also needed.”
  • The definition of “Actionable Marker” aligns with Foundation Medicine’s current content and approach: “Actionable Marker – Documented alterations with supporting data that allow for a benefit-risk assessment of treatment choice, linking the patient to a FDA approved drug, on- or off-label, a drug in the investigational phase of development, or an established prognostic outcome.”
  • The definition of “comprehensive” also aligns with Foundation Medicine’s assays, which cover all four classes of alterations and is a key differentiator for Foundation Medicine: “Panels are a comprehensive (i.e., point mutations, deletions, amplifications, fusions) selection of multi-marker gene assays of cancer driver alterations as opposed to traditional single-marker assays.”
  • The approach to validating assays aligns with Foundation Medicine’s views and alleviates concerns around the need for clinical utility data for every gene on an assay: “Approaches for performing validation studies should be based on the types of alterations measured by the assay, rather than every alteration individually.”
    • The approval of Qiagen’s therascreen EGFR assay is highlighted as an example of an approval where clinical utility was not demonstrated for every mutation: “The working group would like to draw attention to the intended use of the Qiagen therascreen EGFR assay. This approval highlights a creative approach for an assay that has shown clinical utility for multiple mutation classes, and has content that has been analytically demonstrated, but importantly has not been demonstrated to have clinical utility for every mutation. This will be an important precedent to consider in the context of the proposals in this paper.”
    • Focus of validation activities on molecular signature vs. tissue of origin: “To provide greater flexibility, most NGS validation activities should begin with DNA as the starting specimen rather than the original tissue source.”
    • Determination of content supports the comprehensive approach over the narrow/hot spot approach: “Determine the contents of a cancer panel by classifying potential markers based on current utility in clinical care and clinical trials and peer-reviewed publications as well as recognized clinical guidelines.”
    • An overarching, inclusive body determines content, and no one company or organization would own the process: “The working group proposes that panel content could be driven by an international public body that would have an unbiased approach to determining panel content and have the appropriate scientific expertise. It will be critical to also include pharmaceutical companies in these discussions as much of the biological significance of markers will be based on work performed as part of drug development efforts. Finally, ensuring that payers are included in the discussion will be important to ensure commercial viability of the approach.”
    • Regular updates suggested for content, supporting the centralized lab model vs. kitted solutions: “The NGS Working Group further proposes that this list should be modified at least annually.
    • In discussing the landscape, the paper references Lung-MAP and emphasizes the FDA’s support for it: “FDA has supported this trial design with creative and rapid approaches to review both the drugs and diagnostic platforms used in the trial. The Lung-MAP trial is expected to provide data that could support FDA approval of both the drug and associated companion diagnostic.”
    • The group also emphasized the unsustainability of the current CDx model: “Given the rapid pace of drug development that relies on accurate identification of molecular markers to determine whether a drug is appropriate for a particular patient, the current one drug/one test paradigm is inefficient and unlikely to be acceptable in the clinic for much longer.”
    Link to full document HERE.