Clinical Pharmacology Corner: FDA Announces Availability of the Final Guidance “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease”

FDA Announces Availability of the Final Guidance “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease”

On October 15, 2018, the U.S. Food and Drug Administration (FDA) announced the availability of the final guidance for industry entitled “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease”. This guidance replaces the draft guidance that was issued in December 2017. It describes FDA’s current recommendations on how to group patients with different molecular alterations for eligibility in clinical trials and general approaches to evaluate the benefits and risks of targeted therapies within a clinically defined disease where some molecular alterations may occur at low frequencies.

Insights into the molecular basis of disease have led to the development of targeted therapies. Targeted therapies are drugs that act on the molecular changes that cause or contribute to a disease (e.g., changes in DNA, RNA, or proteins). Many clinically defined diseases are caused by a range of different molecular alterations, some of which may occur at low frequencies. While drug developers have been able to develop targeted therapies to treat many genetic diseases and cancers, it is often difficult to determine whether the drug is effective for certain patients whose disease pathology is driven by molecular changes that occur at low frequencies.

This guidance provides drug developers greater clarity on FDA’s recommendations for researching and developing new targeted therapies, including enrolling patients with different underlying mutations, some of which may be rare, into clinical trials for targeted therapies when reasonable scientific evidence suggests the drug could be effective for patients with these genomic findings. Additionally, this guidance specifies the evidence needed to demonstrate effectiveness for a variety of molecular subsets within a particular disease, which could lead to more consistent development and approval of targeted therapies for patients who are likely to benefit from them.  

The “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease” final guidance is available at https://go.usa.gov/xPNND. Please refer to the guidance for more details.

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA