In October 2022, the US Food and Drug Administration (FDA) issued 3 guidance documents for industry, including final guidance on acute myeloid leukemia (AML) drugs and biologic products. This document was originally published in draft form 2 years ago and was updated to address comments received on the draft guidance. The FDA identified 3 factors that contribute to the complexity of clinical development programs in AML: expansion of treatment intent, broadening of the intended population, and development of a wide range of new drug classes as alternatives to cytotoxic drugs. The guidance addresses these factors and provides FDA views on efficacy endpoints, exploratory and confirmatory trial considerations, and regulatory submissions for new drugs. The final guidance also includes editorial changes, clarification of the time frame for marrow sampling and peripheral blood tests to establish complete remission, inclusion of marker-negative patients in studies of targeted therapies, and recommended characteristics for stopping rules.
Two draft guidance documents were also released. One is for characterizing, collecting, and reporting immune-mediated adverse reactions (imARs) in cancer immunotherapeutic clinical trials for treatments such as monoclonal antibodies, anticancer vaccines, and cytokines. This guidance includes recommendations for identifying whether adverse events qualify as imARs and specifies the kind of data the FDA would like to receive when assessing potential adverse events and the type of data that should be included in drug applications.
The other draft guidance is for tissue-agnostic drug development in oncology and includes recommendations regarding tissue-agnostic drugs that target specific molecular alterations across multiple cancer types. This guidance suggests that treatment effects be generalized on the basis of data observed in certain cancer types to other cancer types with the same targeted molecular alteration, which may expedite new treatments for patients with rare cancer types. It also includes recommendations for determining whether a tissue-agnostic drug-development program is appropriate.
These guidance documents, including the final guidance on AML, are intended for use by trial sponsors to facilitate efficient clinical development of drugs and biologic products. Their purpose is to provide recommendations for industry and they should be considered by drug development teams when designing clinical programs.
These guidance documents, including the final guidance on AML, represent the FDA’s current thinking and are not intended to bind FDA or the public. An alternative approach may be used if it satisfies the requirements of applicable statutes and regulations.