USA – FDA issues draft guidance to enhance efficiency in drug development

FDA Commissioner Scott Gottlieb highlighted minimal residual disease (MRD)’s potential as a surrogate endpoint in clinical trials when he unveiled FDA’s draft guidance on using MRD in hematologic malignancy drug development in a statement Monday.

As early as 2012, FDA co-sponsored public workshops « to gain a better understanding of the state of the science of MRD, » the agency wrote in the guidance (see « FDA to Discuss Minimal Residual Disease as Surrogate Endpoint »).

Gottlieb pointed to emerging technologies, such as the newly approved clonoSEQ assay from Adaptive Biotechnologies Corp. (Seattle, Wash.), as contributing to a paradigm shift where MRD assessments could be useful in clinical trials or help expedite development. FDA approved clonoSEQ last month to detect MRD in acute lymphoblastic leukemia (ALL) or multiple myeloma patients. The in vitro diagnostic is capable of detecting MRD at levels below 1 in 1 million cells (see« FDA Approves Minimal Residual Disease Diagnostic »).

As an endpoint, MRD should generally be based on the intent-to-treat (ITT) population, according to the guidance. FDA cautioned that analyses of MRD-evaluable populations, or all patients who achieve a complete response, may not be sufficient to support regulatory submissions or could contain biases. FDA outlined several disease-specific considerations for assessing MRD, including which types of samples to obtain from patients and when.

MRD could also be used in clinical trials as a biomarker to predict or monitor treatment response, as well as a diagnostic or prognostic biomarker, the document added…