FDA issues final guidance on AML drug development, two oncology draft guidances

Regulatory NewsRegulatory News | 17 October 2022 |  By 

The US Food and Drug Administration has published a final guidance and two draft guidances that detail its thinking on developing certain types of new cancer drugs. The guidances are meant to provide advice to sponsors on developing drugs to treat acute amyloid leukemia (AML), reporting certain clinical trial adverse events and developing tissue-agnostic cancer drugs.
On 17 October, FDA released three guidances, including a final guidance titled Acute Myeloid Leukemia (AML): Developing Drugs and Biological Products for Treatment. The guidance was originally published in draft form two years ago and it broadly outlines the agency’s thinking on AML drug development programs and clinical trial designs to support such products, including indications for individual phase of treatment. (RELATED: Draft AML guidance takes targeted therapies into account, Regulatory Focus 17 August 2020)
“New classes of drugs are being developed as alternatives to the standard cytotoxic drugs for the treatment of AML,” FDA notes. “The following factors contribute substantially to the complexity of clinical development programs for such new drugs: the 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 takes those issues into consideration and includes the agency’s views on topics such as efficacy endpoints, exploratory and confirmatory trial considerations and regulatory submissions for AML drugs.
FDA said the final guidance was updated in response to the comments it received on the draft guidance. And now includes several editorial changes, clarifications of the time frame for marrow sampling and peripheral blood tests to establish complete remission, the inclusion of marker-negative patients in studies of targeted therapies and the recommended operating characteristics for safety-stopping rules.
FDA also published a draft guidance titled Characterizing, Collecting, and Reporting Immune-Mediated Adverse Reactions (imARs) in Cancer Immunotherapeutic Clinical Trials. The guidance is meant to help sponsors developing cancer immunotherapeutic drugs that modulate the endogenous immune system and may break immunologic tolerance to normal organs and tissues. The agency provides recommendations on topics such as the kind of data it would like to see collected and evaluated when assessing potential adverse events. It also looks at the kind of data that should be included in drug applications.
Additionally, the agency published a draft guidance titled, Tissue Agnostic Drug Development in Oncology. In it, the agency makes recommendations to sponsors regarding tissue-agnostic cancer drugs that target specific molecular alterations across multiple cancer types.
“A tissue agnostic oncology drug can therefore be used to treat multiple types of cancer (e.g., colorectal, thyroid, and breast cancers) with the targeted molecular alteration (e.g., either the same targeted molecular alteration or targeted molecular alterations affecting a single pathway),” FDA noted. “The guidance discusses the need in tissue agnostic drug development to generalize treatment effects based on data observed in some cancer types to other cancer types with the same targeted molecular alteration, when no subjects (or a limited number of subjects) with the other cancer types were included in the clinical trial(s).”
FDA said such an approach may expedite new treatments for patients with rare cancer types when it may not be feasible to conduct trials in larger populations. In the guidance, the agency asks sponsors to consider factors that sponsors should take into account when deciding whether a tissue-agnostic oncology drug development program is appropriate, such as biology, subject population, clinical pharmacology, and clinical safety and efficacy.
The guidance also describes other issues to consider such as nonclinical assessment, subject selection, study designs, statistical considerations, endpoints, pediatrics, diagnostic considerations, and labeling, as well as postapproval data and information.


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