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Sysmex Inostics Sees Ultra-Sensitive Leukemia Liquid Biopsy as Potential CDx

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This story and headline have been updated from a previous version to clarify that Sysmex Inostics will submit its assay for clearance as needed for any medications it accompanies.

NEW YORK – Sysmex Inostics has developed an ultrasensitive and CLIA-validated next-generation sequencing liquid biopsy assay for detecting minimal residual disease in acute myeloid leukemia, and has partnered with Qiagen to develop and distribute companion diagnostics assays like this one worldwide.

AML-MRD-SEQ utilizes a panel covering 68 regions across 20 genes, and Sysmex claims that it achieves 50 to 100 times greater sensitivity than competing NGS-based assays, such as Illumina's TruSight myeloid sequencing panel and Foundation Medicine's FoundationOne Heme lab-developed test. Based on internal studies and demonstrated in the CLIA validation, Sysmex said that the assay has a limit of sensitivity of approximately 0.035 percent mutant allele frequency, for example, compared to 5 percent in the case of TruSight and approximately 1 percent for FoundationOne Heme.

The high sensitivity, the company said, could enable earlier detection and treatment of MRD. Furthermore, if sensitivity is lacking, "there is a risk of not being able to report a mutation of concern [to] the oncologist," explained Fred Jones, senior director of life sciences and medical affairs at Sysmex.

The greater sensitivity, Jones explained, comes from Sysmex's Plasma-Safe-SeqS technology, essentially a way to subtract out sequencing error noise associated with high-throughput amplification.

"There are barcodes attached to individual molecules, and they're assigned almost like a digital PCR," Jones said.

The barcodes serve as unique identifiers that allow amplification-associated errors to be caught and removed from final analysis. This subtraction method, said Jones, enables Sysmex to achieve "cheap, ultra-high sensitivity."

Sysmex currently offers the assay out of its CLIA lab in Baltimore. It may seek US Food and Drug Administration approval for AML-MRD-SEQ as a companion diagnostic as needed for any medications it accompanies, for which there is not yet any definite timeline.

The AML-MRD-SEQ panel includes several genes that are current therapeutic targets, such as IDH1/2, FLT3, and NPM1, and approval will depend in large part on the approval and efficacy of corresponding drugs.

The assay will serve as a companion to a given drug, Jones explained, "and the drug has to show low toxicity, efficacy, and everything. So, the timelines are indefinite right now with respect to if [a] drug is deemed effective and how important the biomarker assay is in the development and use of that drug."

Pharmaceutical firms will comprise the company's main commercial target for AML-MRD-SEQ until the assay gains CDx approval and insurers cover it. The company can, however, provide the service to oncologists now. Sysmex said that that it has fielded "several" inquiries and is currently conducting pilot projects with various pharmaceutical companies, although Jones declined to say which ones at this time.

"We're working with pharma companies in the companion diagnostics domain," Jones said. "And we fully intend that our methodology will [have] clinical use [as] a companion diagnostic."

Should Sysmex seek FDA clearance of its assay as a CDx, it may get a boost from Qiagen, with whom Sysmex formed a global strategic partnership to develop and commercialize cancer companion diagnostics last summer.

Shinichi Sato, CEO of Sysmex, said in an interview that the partnership leverages the companies' different strengths. "Qiagen has a [good] track record with companion diagnostic development in the United States and globally, but they don't have a great product for NGS," Sato said. Sato later clarified that while Qiagen provides quality NGS solutions, the company lacks a ctDNA panel with the sensitivity that Sysmex offers, highlighting the companies' complementary strengths.

Under the alliance, Sysmex and Qiagen will collaborate to develop CDx assays for pharmaceuticals throughout the stages of drug development, and Sysmex will subcontract to Qiagen for late-stage development, manufacturing, and regulatory clearance of CDx assays. Sysmex will also retain ownership of any commercial products, with rights to distribute them throughout Japan, China, and other parts of Asia, as well as the Middle East and Africa, while Qiagen will retain exclusive rights to commercialize and distribute them throughout the Americas, the UK, and Europe.

The partnership is set to last 10 years, after which it may automatically renew every two years.

The two companies have a longstanding relationship in developing cancer companion diagnostics. Last year, for instance, Sysmex launched the Ipsogen JAK2 DX reagent, used to diagnose certain hematopoietic tumors, through a distribution agreement with Ipsogen, which Qiagen acquired in 2011.

AML-MRD-SEQ adds to Sysmex's growing Safe-SeqS assay portfolio. The company has a head-and-neck cancer assay based on this methodology in the works, which it plans to launch sometime next year, although Jones declined to provide a more specific date.

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