, the U.S. Food and Drug Administration announced. Marketing authorization of the ClonoSEQ assay was granted to Adaptive Biotechnologies.
The ClonoSEQ assay is an in vitro diagnostic test that uses multiplex polymerase chain reaction and next-generation sequencing to identify and quantify certain gene sequences in DNA extracted from the bone marrow from patients with ALL or multiple myeloma. This is a single-site assay collected by the patient’s provider and sent to Adaptive Biotechnologies for evaluation.
The ClonoSEQ assay is capable of detecting minimal residual disease at levels below 1 in 1 million cells. Currently, providers test for MRD using flow cytometry assays or polymerase chain reaction–based assays. Those methods are usually capable of measuring MRD down to 1 in 10,000 or 1 in 100,000 cells.
“Determining whether a patient has residual cancer cells remaining after treatment provides information on how well a patient has responded to therapy and how long remission may last. Having a highly sensitive test available to measure minimal residual disease in ALL or multiple myeloma patients can help providers manage their patients’ care,” FDA Commissioner Scott Gottlieb, MD, said in a press release.
Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the accuracy, reliability, and effectiveness of tests intended to be used as an aid to measure MRD to assess the change in burden of disease during and after treatment. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for these tests, the agency said in the release. This action also creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a previously approved device.
“The FDA is applying novel regulatory approaches to make sure that these rapidly evolving [next-generation sequencing] tests are accurate and reliable. At the same time, we’re seeing more and more laboratory-developed tests seek marketing authorization from the FDA,” he said, adding that the agency has put forward a plan to modernize the regulatory framework for all in vitro clinical tests.
The FDA evaluated data to demonstrate clinical validity from a retrospective analysis of samples obtained from three previously conducted clinical studies including 273 patients with ALL, an ongoing study of 323 patients with multiple myeloma, and a study of 706 patients with multiple myeloma, according to the FDA release.
For patients with ALL, the ClonoSEQ assay was used to assess MRD at various disease burden thresholds to show that the MRD level correlated with event-free survival – the length of time, after treatment, that the patient remains free of certain complications or events. Patients whose ClonoSEQ assay result was MRD negative had longer event-free survival, while patients with higher MRD assay results had lower event-free survival. Similar patterns of results were seen for progression-free and disease-free survival in patients with multiple myeloma.