NEW YORK (GenomeWeb) — The US Food and Drug Administration on Friday granted de novo premarket authorization to Seattle-based Adaptive Biotechnologies' ClonoSeq, a next-generation sequencing test for measuring minimal residual disease (MRD) in acute lymphoblastic leukemia or multiple myeloma patients.
In reviewing ClonoSeq through the de novo premarket review pathway for new low-to-moderate-risk devices, the agency also put forth its regulatory expectations for these types of tests via special controls. "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," the agency stated, explaining that devices of this type can now obtain marketing authorization by demonstrating substantial equivalence to a predicate device.
An estimated 6,000 people in the US will be diagnosed with ALL and 31,000 people will be diagnosed with multiple myeloma this year. In patients with these diseases, MRD is a metric for gauging how many cancer cells remain in their bone marrow after treatment, which can be indicative of their response to treatment and extent of their remission. "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 said in a statement.
Currently, MRD is measured using flow cytometry assays or PCR-based assays, which can pick up 1 in 10,000 or 1 in 100,000 cells. ClonoSeq, which can only be performed at Adaptive's lab, employs multiplex PCR and NGS to quantify gene sequences of interest in the bone marrow of ALL and multiple myeloma patients, and can measure MRD at levels below 1 in 1 million cells.
The FDA's authorization of ClonoSeq was based on retrospective analysis of three studies that together involved samples from 273 ALL patients and more than 1,000 multiple myeloma patients. ALL patients who were MRD negative had longer event-free survival (the time after treatment that a patient is free of complications or other events), while those with higher MRD results had lower event-free survival rates.
ClonoSeq was used to demonstrate that MRD was similarly associated with progression-free survival (the amount of time during and after treatment that a patient's disease doesn't get worse) and disease-free survival (the length of time after primary cancer treatment that a patient doesn't have any signs of that cancer).
Following the agency's authorization of ClonoSeq, Greg Friberg, Amgen VP of global development for oncology, highlighted in a statement that the FDA earlier this year approved Blincyto (blinatumomab) for B-cell precursor ALL patients who are in remission but still have minimal residual disease. These patients now have an FDA-cleared, NGS-based MRD assay that doctors can use to guide treatment decisions and help them acheive MRD negativity, Friberg said. He added that Amgen will continue to collaborate with Adaptive to further explore MRD as a biomarker.
ClonoSeq's market authorization represents the agency's ongoing efforts to streamline regulations for NGS tests. For example, in authorizing Memorial Sloan Kettering Cancer Center's MSK-IMPACT NGS tumor profiling assay last November, the agency also established a Class II regulatory pathway for similar cancer panels, allowing them to become eligible for the 510(k) clearance process either by applying to the FDA or going through New York State's Department of Health as a third party reviewer.
With the MSK-IMPACT decision, the FDA also recognized the challenge of regulating NGS panels, which can analyze an indefinite number of genes, and outlined a tiered framework for the level of evidence labs would need to submit to the agency based on how certain biomarkers would be used in patient care. Earlier this year, the agency also finalized guidances on using public genetic variant databases to support the clinical validity of genetic and genomic based tests; and the design, development, and analytical validation of NGS tests in diagnosing germline diseases.
According to Gottlieb, the agency's efforts in this regard have spurred more labs to pursue the FDA regulatory pathway. "The FDA is applying novel regulatory approaches to make sure that these rapidly evolving NGS tests are accurate and reliable," he noted in the statement. "At the same time, we're seeing more and more laboratory-developed tests seek marketing authorization from the FDA."
The agency has incorporated some of these ideas into a new regulatory framework for all diagnostics and recently communicated them to the House Energy & Commerce Committee, which is working on a draft bill called the Diagnostic Innovation and Accuracy Act.
"We believe that to more fully unlock these innovations, we need to modernize the regulatory framework for all in vitro clinical tests," Gottlieb added, referencing the FDA's proposed framework. "We believe such an approach can promote the development of safe, effective technologies that have the greatest potential to help us diagnose, treat and cure disease."