Author: [AUTHOR] Published on 2/17/2023 6:00:00 AM
FDA Announces Availability of a Draft Guidance on Optimizing Dosing for Cancer Treatments
On January 17, 2023, the US Food and Drug Administration(FDA) announced the availability of a draft guidance for industry entitled
Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases. This guidance is intended to assist sponsors in identifying the optimal dosage(s) for human prescription drugs or biological products for the treatment of oncologic diseases during clinical development prior to submitting an application for approval for a new indication and usage.
Dose-finding trials for oncology drugs have historically been designed to determine the maximum tolerated dose (MTD). This paradigm was developed for cytotoxic chemotherapy drugs based on their observed steep dose-response, their limited drug target specificity, and the willingness to accept substantial toxicity to treat a serious, life-threatening disease. Sponsors typically administered the MTD, or a dosage close to the MTD, in subsequent clinical trials without further efforts to optimize the dosage.
Most modern oncology drugs, such as targeted therapies, demonstrate different dose-response relationships compared to cytotoxic chemotherapies, such that doses below the MTD may have similar activity to the MTD but with fewer toxicities. Nevertheless, the dosage administered in a registration trial for these targeted therapies is often the MTD or the highest dosage administered in the dose-escalating trial if the MTD is not defined. Therefore, the MTD paradigm can result in a recommended dosage that is poorly tolerated, adversely impacts functioning and quality-of-life, and moreover, affects a patient’s ability to remain on a drug and thereby derive maximal clinical benefit. A more informed approach to identifying the optimal dosage(s) for the treatment of oncologic diseases is to investigate a range of dosages and select the dosages to be further investigated based on clinical data and an understanding of dose- and exposure-response relationships. With sufficient planning, identifying an optimal dosage(s) can be aligned with the goal of expediting clinical development, and strategies to optimize the dosage can be merged into a seamless development program.
Please refer to the “
Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases” guidance for more details. FDA is publishing this draft guidance to collect additional public comments. To ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit your comments regarding the draft guidance to the docket (Docket No. FDA-2022-D-2827) available at
https://www.regulations.gov up to 60 days following publication in the FEDERAL REGISTER. However, you may submit comments to the docket at any time. This guidance, when finalized, will represent the current thinking of the FDA on this topic. It does not establish any rights for any person and is not binding on FDA or the public. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience and make your voice count.
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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.