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IntegraGen Prepping miRNA-based Colorectal Cancer Assay for CE Mark; Exploring CLIA Options for US

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French molecular diagnostics and clinical genomics services firm IntegraGen said this week that it has obtained exclusive rights to a microRNA biomarker that can help predict therapeutic outcomes in non-KRAS mutated metastatic colorectal cancer patients being treated with epidermal growth factor receptor inhibitors.

With the license in hand, IntegraGen is now focused on obtaining CE marking for a real-time PCR-based diagnostic kit that clinical laboratories in Europe would be able to use to measure expression of the biomarker, hsa-miR-31-3p, in formalin-fixed, paraffin-embedded tumor samples — an effort it is undertaking with the help of previously disclosed collaborator Lab21.

In addition, IntegraGen is currently "exploring options" in the US to bring the assay to market as a laboratory-developed test in a CLIA lab, though not necessarily one of its own, Larry Yost, general manager at IntegraGen and head of US operations for the company, told PCR Insider.

"We have a business office in the US [in Cambridge, Mass.], but we do not have a CLIA-certified lab," Yost said. "We've had discussions with numerous [parties] who are interested in what we're doing and how this may fit in [commercially] with what they are doing, but we're still in that process."

IntegraGen, headquartered in Evry, France, derives the bulk of its revenues by providing genomic services such as DNA extraction, next-generation sequencing, SNP genotyping, and methylation analysis to both academic and biopharmaceutical customers. In particular, the company has recently been very active in the whole-exome sequencing space, Yost said.

It was a relationship with one of these service customers — the laboratory of genetic and clinical oncology research Pierre Laurent-Puig at the European Georges Pompidou Hospital University Paris Descartes — that paved the way for its recently announced licensing deal.

"This partnership was initiated two-and-a-half years ago based on [Laurent-Puig's] fundamental research," Francois Liebaert, vice president of R&D and medical affairs at IntegraGen, told PCR Insider. "It's a good thing to have a biomarker, but first it needs to be a good biomarker, and second you need to be able to measure it [accurately]. This was our major input: directing the development strategy and … technology-development process … in order to make this actionable in daily [clinical] practice," Liebart said.

Laurent-Puig's lab has demonstrated that the expression of the hsa-miR-31-3p microRNA can predict progression-free survival in CRC patients treated with anti-EGFR therapy. At the European Society for Medical Oncology's annual meeting held earlier this year, Laurent-Puig's lab presented data from these studies.

According to a poster from the meeting, mutations in the KRAS gene are known to trigger resistance to EGFR inhibitors. As part of an effort to find biomarkers that could predict responses to these drugs in wild-type KRAS mCRC patients, the researchers extracted and analyzed RNA from fresh frozen tumor samples from 43 patients randomly chosen from two separate training sets.

In those studies, expression of miR-31-3p displayed a significant association with progression-free survival, prompting Laurent-Puig and colleagues to expand their study to include an additional 89 KRAS wild-type CRC patients, which revealed that metastatic CRC patients with poor prognosis overexpressed hsa-miR-31-3p and showed no response to anti-EGFR therapy.

"With approximately two-thirds of metastatic colorectal cancer patients being wild-type KRAS, the incorporation of this marker into clinical practice will likely help to better target the use of EGFR therapy in large numbers of patients, spare patients who will likely not respond to these agents from their associated toxicities, and also prevent the loss of time and opportunity to receive other treatment options which may be more effective," Laurent-Puig said in a statement this week.

IntegraGen obtained an exclusive license to the intellectual property protecting the biomarker from Descartes University, the French Institute of Health and Medical Research, the French National Center for Scientific Research, and the Public Support Hospitals of Paris, all of which co-own the IP.

IntegraGen also earlier this year inked an agreement with UK-based clinical diagnostics developer Lab21 — some of the assets of which have since been acquired by Irish diagnostics firm Trinity Biotech — to develop the microRNA assay (PCR Insider 2/28/2013). Under the agreement, Lab21 was to help IntegraGen develop the kit using its proprietary SPARQ PCR technology to detect expression levels of hsa-mir-31-3p.

IntegraGen's Liebaert said this week that IntegraGen has developed the test to this point using standard "TaqMan-type" real-time PCR technology, but it also is in the process of conducting studies to determine whether a test using the Lab21 technology will provide similar results.

The appeal of Lab21's SPARQ technology, according the company, is that it "circumvents the use of other primers and probes weighed down by expensive licensing costs" and enables "time- and cost-efficient development and manufacture of very sensitive and specific real-time PCR assays suitable for any real-time PCR platform." Lab21 has not disclosed additional details about the technology.

Liebaert said that IntegraGen will likely validate its assay on a number of real-time PCR platforms so that the test may be widely adopted. "We are pretty confident that it will be kind of a universal kit that could be used on different platforms," he said.

Liebaert added that, besides working toward CE marking, IntegraGen still needs to determine a manufacturing partner for its assay.

In terms of penetrating the US market, IntegraGen will likely look to partner with an existing CLIA lab rather than build out its own — a strategy it has already employed with its lone commercial offering in the states, a SNP genotyping-based risk assessment test for children with autistic siblings.

"We have a contracted CLIA lab that we run the test through," Yost said. "The difference with the microRNA test … is that it's a much different, older population, and some of the beneficiaries would be Medicare recipients, so you're dealing with different requirements from a CLIA and billing perspective. So we would not be able to run [the miRNA test] from the lab that we're doing the autism test in."

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