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NanoString on Track to Launch Breast Cancer Subtyping Test in EU with CE Mark, in US with FDA OK

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After establishing a new diagnostics unit in May, NanoString Technologies is planning to launch its flagship Breast Cancer Intrinsic Subtyping Assay in European markets with CE marking by year end and in the following 12 months file a 510(k) application with US regulators.

Nearly three months ago, NanoString launched a diagnostics division to commercialize its flagship Breast Cancer Intrinsic Subtyping Assay, as well as other tests that can help doctors tailor drugs and treatment strategies to molecularly defined patient populations.

The goal of the diagnostics division "is to enable … personalized medicine on a globally distributed basis and offer a menu of diagnostic tests for cancer that can be run on our proprietary nCounter system in clinical labs worldwide," Bruce Seeley, senior VP and general manager of the diagnostics unit, told PGx Reporter.

The first test the unit will launch will be the Breast Cancer Intrinsic Subtyping Assay, which uses the PAM50 gene signature that the company has exclusively licensed from Bioclassifier. The test measures 50 classifier genes and five control genes and categorizes patients into four intrinsic breast cancer subtypes that confer prognostic information: luminal A, luminal B, HER2-enriched, and basal-like.

The subtyping assay and the nCounter platform are currently available for research use only. ARUP Laboratories of Salt Lake City markets a laboratory-developed version of the test that runs on an RT-PCR platform. With regulatory clearance, NanoString hopes to sell its test as a tool that can help doctors gauge whether patients are at high or low risk of breast cancer recurrence, and make personalized treatment decisions.

Previously, Seeley was involved in the commercialization of the lymphoma drug Adcetris at Seattle Genetics and led the launch of the pharmacogenetically targeted breast cancer drug Herceptin at Genentech. He said that before he joined NanoString earlier this year, conversations with industry stakeholders had signaled to him that healthcare providers are increasingly thinking about breast cancer in terms of molecular subtypes.

"When I was at Genentech, it was just the beginning [of personalized medicine], but people were already starting to talk about breast cancer by subtypes," Seeley recalled. "So, this has been around for years now and it's something that is part of the vernacular. Part of the way that you talk about breast cancer now is by subtypes."

Professional treatment guidelines recommend that doctors consider patients' molecular subtypes in treating breast cancer. For example, a panel of oncologists at the St. Gallen International Breast Cancer Conference in March 2011 advised that doctors should no longer consider breast cancer as a single disease. "Subtypes can be defined by genetic array testing or approximations to this classification using immunohistochemistry," the panelists wrote. "These subtypes have different epidemiological risk factors, different natural histories, and different responses to systemic and local therapies." (PGx Reporter 7/27/2011).

The St. Gallen experts recommended that clinicians "should consider cases within the various distinct [breast cancer] subtypes in order to properly assess the relevant evidence and arrive at appropriate therapeutic advice."

Launch Preparations

In preparation for the forthcoming launch of the breast cancer test, NanoString has been conducting validation studies to support its regulatory approval in various markets.

At the San Antonio Breast Cancer Symposium last year, NanoString presented results from the first clinical validation study involving the PAM50 gene signature, which compared it against the market leader, Genomic Health's Oncotype DX breast cancer recurrence test. In the study, researchers led by Mitch Dowsett of the Royal Marsden Hospital analyzed 1,000 patient samples from the TransATAC trial and reported that the PAM50 prognostic score assigned 21 percent fewer estrogen-receptor-positive, node-negative breast patients to the intermediate risk group than did Oncotype DX, and deemed a portion of these patients to be at high risk of recurrence (PGx Reporter 12/14/2011).

In May, NanoString launched the second validation study for the test, in which the firm aims to analyze 1,000 patient samples and gauge how well the PAM50 gene signature predicts whether patients previously enrolled in the Austrian Breast & Colorectal Cancer Study Group 8 trial were at high risk of breast cancer recurrence. The ABCSG8, originally launched in 1996, showed that treating early-stage breast cancer patients with tamoxifen and then anastrozole decreased recurrence rates by 20 percent compared to those receiving just tamoxifen.

"We realize that success in the diagnostics arena is going to require a strong foundation in superior clinical data, because that's what I need to convince customers to buy the PAM50 kit," Seeley said. "Advertising and marketing is one thing, but if we don't have the clinical data to support the product, people aren't going to buy it.

"We've got a very aggressive approach to getting the information to the agencies for the clearance," he added. "And we're on track for both the CE Mark and the 510(k) clearance."

NanoString identifies Genomic Health, Agendia, and Sividon Diagnostics in Europe as potential competitors in the molecular diagnostics space. Differentiating its test from others on the market will require NanoString to form a sales force. For the time being Seeley is one of the few employees running the firm's commercial operations. NanoString recently hired Dale Levitzke as the VP of global sales for life sciences. Seeley said he is in the process of outfitting the company with a sales team that can market the test to oncologists and pathologists.

The firm is also assessing the level of clinical validation and cost-effectiveness data it will need to sway private and government payors to reimburse for the breast cancer subtyping test. "We're at the point where we are strategizing about reimbursement both in the Europe and in the US," Seeley said.

In both those markets, "there is a tremendous pent-up demand for quality genetic testing. People really want to offer this for their patients, not just because it's beneficial in helping treat their patients, but the payors are interested in it because it can potentially help them save money," he added. "So, it's a win-win for patients, for physicians, and for payors."

Although NanoString will attempt to position its Breast Cancer Intrinsic Subtyping Assay mainly as a competitor to Genomic Health's Oncotype DX breast cancer recurrence test, Seeley acknowledged that the company will be looking to Genomic Health's experience in establishing coverage for Oncotype DX with the majority of US insurers. "Genomic Health has been at this for a long time and it took them quite a long time to secure reimbursement," he noted. "For us, we've got good data. The work that Genomic Health has done, both with public and private, suggests that the reimbursement environment has been paved somewhat by [their] good work."

In its effort to establish a successful diagnostics commercialization trajectory for its tests, NanoString has even hired some former Genomic Health employees. For example, Chief Medical Officer J. Wayne Cowens, who is leading clinical development for the breast cancer subtyping test, was formerly VP of clinical oncology at Genomic Health. There he played a leadership role in designing many of the clinical validation studies for Oncotype DX in various forms of cancer.

"[Cowens] brings an extensive amount of experience in the field including developing health economic studies designed to support reimbursement for Oncotype DX," Seeley said. "So, he's bringing that expertise to NanoString and that's an important component for us as we bring forward not just our clinical regulatory approach but also our health economics approach." Seeley noted that Cowens has hired former FDA employees and people with regional regulatory expertise who will shepherd NanoString's tests through the regulatory filing process in different markets.

Pharma Partners

The growing awareness of breast cancer subtypes is also opening doors for NanoString in terms of partnerships with drug developers. According to Seeley, the company's test platforms are being used by pharma and biotech for toxicology and translational research, as well as on the discovery side.

"We have been in discussions with a variety of biotech and pharma companies about companion diagnostics. Keep in mind that presently around 25 percent of our life sciences [business] comes from pharma," Seely said.

"We've got a following within the pharma/biotech research community in that they are continually using our nCounter products to come up with new ideas," he continued. "So, when they come up with a new idea or they have a new product, we already have that relationship with these companies for a companion diagnostics approach."

At the American Society of Clinical Oncology's annual meeting this year, NanoString held discussions with several drug developers, and Seeley said it was clear that these firms recognize the value of a diagnostic that can determine breast cancer recurrence risk based on a molecularly defined disease subtype.

"It is the increasing acceptance of intrinsic subtyping to define breast cancer that's driving quite a bit of interest in [the] PAM50 [gene signature] and partnering with NanoString on companion diagnostics," Seeley said. "If you have a drug that you need to develop in breast cancer, it's increasingly known that you've got to know what your molecular profiling assay is going to be. You've got to use intrinsic subtyping to define your population in breast cancer.

"What was interesting to me while I was at ASCO is that the pharma/biotech companies have really focused on their breast cancer drugs and they've realized that they need to know what the subtype is … to enrich the population before they start [clinical trials] and after the trial is over they can define response by subtypes," he said.

For the time being, NanoString will primarily focus in developing molecular diagnostics for various forms of cancer.

The company currently has a pipeline of platforms that allow users to assess gene expression, copy number variations, and microRNA activity. Via color-coded molecular barcodes and single-molecule imaging, NanoString's nCounter system allows users to measure gene expression or copy number. CEO Brad Gray told PGx Reporter that the nCounter system is being used actively in research in the immunology and inflammation space, as well as to study infectious diseases and stem cells.

NanoString earlier this year also launched its Plex2 Expression Assay Kit, through which users can measure up to 200 targets in up to four samples in a single tube. The company also markets the Cancer Copy Number Assay Kit, which enables analysis of 86 genes that are commonly amplified or deleted in many cancer types. Finally, the firm's Human v2 miRNA Expression Assay Kit lets researchers profile 800 of the most highly expressed miRNAs in a single tube without the need for amplification.

When it comes to developing tests beyond the Breast Cancer Intrinsic Subtyping Assay, "we have some ideas of our own and we have some folks that are bringing some interesting ideas to us," Seeley said, without elaborating.

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