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Genection's AML Panel First of Several NGS-based Dx Tests it Plans to Bring Through FDA Clearance

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NEW YORK (GenomeWeb) – Genection, a subsidiary of Invivoscribe Technologies, has launched a next-generation sequencing-based panel for acute myeloid leukemia — the first of several NGS-based cancer tests that it intends to submit to the US Food and Drug Administration for 510(k) clearance.

San Diego-based Genection, which was launched in 2012, is combining its sequencing analysis capabilities with its parent company's expertise in hematological diseases, and specifically AML, to launch the panel, dubbed MyAML.

Genection originally formed around the idea of streamlining the analysis portion of exome and whole-genome sequencing tests by connecting clinicians and patients with genetic testing and counseling, Brad Patay, Genection's chief medical officer, told GenomeWeb.

"We had created a pathway in a HIPAA-compliant secure system to offer pre- and post-test counseling," he said. However, that model has struggled due to reimbursement issues, he said.

Invivoscribe currently tests for FLT3 and NPM1 mutations in AML patients using traditional PCR and capillary electrophoresis sequencing methods. FLT3 and NPM1 are known biomarkers that are typically tested for as part of standard of care, and both the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing for mutations in those genes. Mutations in FLT3 can predict a patient's likelihood to respond to therapy as well as recurrence risk, while NPM1 mutations have been linked to better outcomes in patients without FLT3 mutations.

Invivoscribe CEO Jeffrey Miller said that last year the company tested more than 12,000 AML samples.

Despite the availability of these biomarkers, AML is still a tough disease with typically poor outcomes, Patay said. Of the approximately 50,000 new leukemia cases each year, around 18,000 are AML cases, and the disease causes 10,000 deaths annually — 43 percent more than other leukemias, he added. "There is a need in the community for a better assay that better stratifies risk and hopefully points to better potential therapies," Patay said.

One problem with treating AML is that patients are typically older when they are diagnosed. The average age of diagnosis is 67 and those patients often "can't go through typical chemotherapy or receive bone marrow transplants," Patay said. "What's needed is targeted therapy."

Patay added that unlike some solid tumors like lung or breast cancer, AML typically has very few somatic mutations, making it possible to capture the vast majority of potential mutations in a patient in one targeted assay. For all those reasons, he said, the firm decided that an AML panel made sense for an NGS-based diagnostic.

The MyAML panel covers 194 genes, including all of the exons as well as around 36 hotspots in intronic regions known to contain breakpoints for gene fusions. The company sequences to a depth of around 1,000x and uses Illumina's MiSeq with paired end reads of 300 bp. The company uses a proprietary bioinformatics pipeline called MyInformatics for analysis.

The test can detect somatic mutations down to a 5 percent allele frequency, which Miller said would allow them to assess the "subclonal architecture to start to see which mutations may be associated with relapse." The goal is to detect those relapse-associated mutations early, before relapse occurs, and "maybe make a difference," he said.

The depth of coverage and long reads are what enable the test to detect fusions and translocations, Patay said, including both known fusions as well as fusions that include a novel gene partner. "It's what sets us apart," he said.

The test uses DNA extracted from blood or bone marrow, and has a turnaround time of one to two weeks.

Genection will run the assay out of another Invivoscribe subsidiary in San Diego, the Laboratory for Personalized Molecular Medicine (LabPMM), which has CLIA certification and CAP accreditation, as well as a LabPMM facility in Germany that has ISO 13485 certification.

Miller said the company would offer the test as a service to ordering physicians to stratify patients and would also look to partner with pharmaceutical companies to run it in the context of clinical trials in order to identify eligible patients.

At least initially, the majority of customers would be pharmaceutical companies, a number of which are already using the test, Miller said.

The test has a list price of $5,000. While the company will bill insurance companies, Miller said that it is still too early to know whether payors will cover it. By comparison, Foundation Medicine has said it receives an average of $3,600 per test, which includes both commercial and government payors.

The MyAML test will likely compete with Foundation Medicine's FoundationOne Heme, which sequences DNA from 405 cancer-related genes as well as the RNA of 265 genes.

Patay said that Genection hopes to distinguish its test from Foundation's both by its focus on AML-related genes, as well as its longer read lengths. "We went after what drives AML and are not looking at other genes or other pathways of hematological genes in general," he said.

In addition, he said MyAML identifies gene fusions by uncovering the break points solely through DNA sequencing, as opposed to also including RNA sequencing. "Because of the depth and length of the sequencing, we can identify novel fusion partners," he said.

FDA clearance

Genection ultimately hopes to bring the MyAML test through FDA clearance as a companion diagnostic, Miller said, a process that he anticipated would take another two to three years. NGS-based companion diagnostics are "new territory both for the diagnostics and medical device companies, as well as the FDA," Miller said.

The test was developed and will be run within a certified controlled quality system laboratory, Miller said, so that will facilitate the process of bringing it through FDA clearance. "We don't have to step back and reinvent," he said.

The company has already begun talks with several pharmaceutical companies that would want to submit the test as a companion diagnostic. The assay could serve as a CDx for multiple drugs, Miller said.

Illumina is pursuing a similar strategy with an oncology panel it is developing. It has struck agreements with AstraZeneca, Janssen Biotech, and Sanofi to develop an NGS-based universal companion diagnostic for solid tumors, which it plans to bring through FDA clearance.

Genection also plans to develop a suite of other NGS-based products that focus on hematological cancers, and is considering panels for myelodysplastic syndromes and myeloid leukemias, Patay said. The company added that it would make additional announcements about its future products in the coming weeks and months.

Invivoscribe also offers RUO NGS assays dubbed LymphoTrack to assess B- and T-cell gene rearrangements, which can be used to identify and track residual disease in lymphomas. The assays can be run on either the Illumina MiSeq or Thermo Fisher Scientific's Ion PGM and they identify clonal rearrangements in IGH V-J and TRG V-J.

In addition, the company has an ongoing collaboration with Novartis to develop a companion diagnostic to identify FLT3-positive AML patients who would be eligible for Novartis' drug midostaurin, a small molecule inhibitor of FLT3 tyrosine kinase. That test will use PCR and capillary electrophoresis sequencing, Miller said. 

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