FDA Finalizes Guidance on Targeted Therapies in Rare Genetic Subsets

The US Food and Drug Administration (FDA) on Monday finalized guidance on developing targeted therapies in rare molecular subsets of diseases.
 
The 9-page guidance finalizes a draft version released in December 2017 and has been updated to incorporate comments submitted to the public docket and includes minor edits to improve clarity.
 
“By providing clarity on the regulatory and scientific frameworks for product developers, safe and effective targeted treatments can be identified with scientifically valid tests and ultimately, made available to patients more efficiently,” said FDA Commissioner Scott Gottlieb.
 
The focus of the guidance is to provide sponsors of targeted therapies with recommendations on grouping patients with different molecular alterations in clinical trials and advice on evaluating the benefits and risks of targeted therapies in diseases with rare molecular alterations.
 
“Although variability in drug response has long been recognized in drug development, targeted therapies present new challenges in addressing the heterogeneity in drug response because the pharmacological effect of a targeted therapy is often related to a particular molecular alteration,” FDA writes.
 
The guidance also discusses the generalizability of findings from clinical trials for rare molecular subsets, labeling considerations and approaches to refining the target population or indication of a drug after its initial approval.
 
In a change from the draft version, the final guidance explains that in some situations, such as to address an unmet medical need, sponsors may include patients in clinical trials who have molecular alterations that are less likely to respond to a drug or whose likelihood to respond is unknown.
 
“In this setting, the sponsor has the option of either splitting study alpha assessment of the primary efficacy endpoint between a subgroup of patients with specific molecular alterations of interest and a broader enrolled population or using an adaptive design with interim assessments of efficacy,” FDA writes.
 
The agency also says that sponsors may instead limit the assessment of the primary efficacy endpoint to only the subgroups of interest and enroll additional subgroups to gather preliminary clinical data in those groups.
 
Federal Register Notice, Guidance, Statement