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FDA Issues New Framework for Oncology Drug Development
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The FDA today issued new guidance to help drug developers select endpoints for marketing applications with the goal of advancing the efficient development of cancer drugs and biologics.
The guidance — titled Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics — is the first update on this framework in more than a decade and replaces the 2007 guidance.
“As part of FDA’s strategy to continue to encourage the modernization of clinical trials, we’re providing new recommendations for drug developers regarding the most effective clinical trial endpoints to help advance the development of products to treat cancer,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “Over the past several decades, we’ve seen an evolution in cancer care in how treatment effect is measured, and which endpoints are successful measures of disease activity or clinical benefit to patients.
“As part of these advances, there’s been a robust debate about the use of surrogate endpoints to support both traditional and accelerated approvals,” he added. “We’ve engaged patient and health care professional communities to inform our regulatory decision-making around these issues, to ensure we are keeping pace with the science and continuing to encourage development of treatments that offer meaningful results for patients.”
The update includes expanded information on oncology endpoints and provides new resources, references and examples of prior regulatory approvals. It also clarifies how oncology endpoints can support traditional or accelerated approval and what factors are used in those determinations.
In addition to OS, endpoints based on tumor assessments include DFS/EFS, objective response rate, complete response rate, time to progression and PFS, and time to treatment failure.
The guidelines also address the role of — and occasional problems with — specific symptom endpoints, including symptom improvement, time to progression of cancer symptoms, and a composite symptom endpoint or scale.
Although blood or body fluid-based biomarkers have not been used as endpoints to support cancer drug approval, the document acknowledges paraprotein levels in blood and urine have been used as part of myeloma response criteria, and durable major molecular response is a surrogate endpoint used for traditional approval for therapies in chronic myeloid leukemia.
Blood-based markers also have been used in composite endpoints, such as when increases in CA-125 were considered as evidence of ovarian cancer progression in conjunction with certain clinical events.
The guidance also suggests that any sponsors planning a trial with an emerging endpoint — which, in the past, has included the use of minimal residual disease for accelerated approval of therapy in acute lymphoblastic leukemia, and metastasis-free survival as an endpoint for approval in nonmetastatic castration-resistant prostate cancer — meet with the applicable FDA office or division prior to trial initiation.
“Applying the most efficient clinical trial designs and using meaningful endpoints that measure benefits important to patients is key to our efforts to modernize clinical trial development programs,” Gottlieb said. “It helps make research and development more effective and can lower the cost of bringing safe and effective treatments to patients.
“We continue to encourage companies to engage with FDA early in the drug development process so that we can work with them to apply modern and efficient trial designs, as well as explore novel endpoints, such as minimal residual disease, which recently formed the basis of approval for a new treatment for a type of leukemia,” he added.
For more information:
FDA. Clinical trial endpoints for the approval of cancer drugs and biologics. Available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071590.pdf. Accessed on Dec. 19, 2018.