By Monica Heger
This story was originally published June 17.
A new program funded by the UK government aims to bring sequencing-based cancer tests to the market as part of a broad initiative to fund research into personalized medicine.
The UK's Technology Strategy Board recently announced that it would fund six tumor-profiling projects with a total of £5.8 million ($9.4 million) under its Stratified Medicine Innovation Program. Three of the projects, led by Life Technologies, Source BioScience, and Oxford Gene Technologies, plan to use next-gen sequencing for tumor profiling and ultimately aim to develop tests based on the technology. The groups are planning these tests for several platforms, including the Ion Torrent PGM and Illumina HiSeq.
The Technology Strategy Board has set a number of requirements for the tumor profiling tests. Each must screen for at least 22 specified mutations in nine known cancer genes: KRAS, BRAF, TP53, PI3KCA, UGT1A1, PTEN, CYP2D6, EFGR, and CKIT. Additionally, the test must cost less than £300 ($450), have a clinically relevant turnaround time, and have the capacity to "grow in line with future demands."
In addition, the TSB expects each test to be applicable for breast, ovarian, colorectal, lung, and prostate cancers, as well as malignant melanoma. Around 9,000 tumor samples will be available to the groups for validating their tests through three genetic testing laboratories that will be designated "technology hubs" as part of the Stratified Medicine Program.
While each of the three sequencing-based projects is taking a slightly different approach, all will be developing targeted tests.
LifeTech: Basic and Comprehensive Panels
Life Technologies plans to develop a 150-gene panel test on the Ion Torrent PGM with two methods of reporting the results. Physicians can either order a simpler report covering nine genes, or a more comprehensive 150-gene report.
The company has partnered with pharmaceutical companies AstraZeneca and Johnson & Johnson, as well as the University of Oxford.
The nine-gene option will report back only the mutations specified by the TSB. The more comprehensive option includes genes that AstraZeneca and J&J have identified for which they either have drugs in development, or plan to develop drugs for.
According to Martin Naley, head of medical next-gen sequencing at Life Tech, the comprehensive report will "add more depth, not just more genes." In that report, the physician would not only see the medically relevant mutations, but would also get a list of clinical trials for which the patient would qualify, based on his or her mutational profile.
Once available, the test will comprise a single panel that will sequence all 150 genes, but would vary based on the data that is reported back to physicians. The more focused version of the test would report only the 30 or so mutations that are clinically actionable for the nine genes specified by the TSB, while the complete version would report variants for all 150 genes.
For example, "in the KRAS gene, there are seven known SNPs that are used today in healthcare," Naley said, so those would be the only KRAS variants reported in the nine-gene version of the test. However, if a physician later decided he wanted the more comprehensive version, that data would be available from the initial sequencing run.
Additionally, the test will sequence the full length of each gene, so as additional actionable mutations are discovered, they can be included in the report.
Naley said the test would be available to the three technology hubs by 2012. Additionally, team plans to begin a clinical trial with the University of Oxford for a separate group of 1,500 patients.
In this trial, patients would give informed consent and be returned medically relevant results via their oncologist. Aside from collecting information about the test results itself, the Life Tech team would also collect information about the clinical decisions made by the doctor, whether those results helped guide or change treatment decisions, and if patients had a better outcome as a result.
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The pharmaceutical collaborators are also providing some funding for the project, which Naley said would cost "several million pounds" and also include the funding awarded by the UK Technology Strategy Board. The pharma partners would then have access to patients' anonymized data, in order to help them design drug trials, identify adverse responses to their drugs, and stratify patients by tumor profile.
Source BioScience: Eying MiSeq
Life science services firm Source BioScience is leading a separate team that includes researchers from Illumina and the Barts Cancer Institute. The team is developing a multi-gene sequencing based test on the HiSeq and potentially the MiSeq, according to Cliff Murray, head of research and development at Source BioScience.
The team's test will initially include between 15 and 20 genes, including the nine specified by the Technology Strategy Board, but "I can see that number growing," Murray said.
He said that while the test will initially be developed on the HiSeq, the team will also have access to the MiSeq. It will most likely be marketed on the MiSeq because the machine is more suited for targeted, clinical applications, he said.
Murray explained that since the test will be marketed to clinicians and hospitals, it makes more sense to offer it commercially on the MiSeq. The HiSeq, which has a current list price of $690,000, "is well outside the budget of most hospitals," he said, while the MiSeq, planned for launch in the third quarter of this year with a list price of $125,000, is much more affordable.
Source BioScience will initially be looking to commercialize its test as a service, Murray said, but could later commoditize it as a kit, or as a package with the MiSeq. "We don't have a clear strategy on that yet," Murray said. "But we'll initially offer it as a service."
OGT: A 'Clinical Decision Tree'
The third group developing a targeted sequencing-based cancer test is led by Oxford Gene Technologies, which just recently started offering next-gene sequencing services (IS 5/31/2011). OGT is collaborating with the University of Southampton, University of Birmingham, and CIS Healthcare, which develops software for the healthcare sector.
James Clough, OGT's vice president of clinical and genomic solutions, said that the company is considering both the Illumina HiSeq and Life Technologies' SOLiD system for its test. It may also consider the MiSeq, he said.
While the team is still deciding on a target enrichment protocol, OGT is a certified service provider for Agilent. It plans to use its custom in-solution Sure Select capture technology for its sequencing services business, and will likely use that technology for the cancer test as well.
The OGT-led team will develop its test based on the 30 mutations specified by the TSB, Clough said.
He said that partnering with CIS Healthcare affords the team an opportunity to develop high-quality analysis tools to complement the test.
CIS Healthcare has "patient prescription management software, and the aim is to development treatment algorithms," Clough said. So, for example, a result could say, "if a patient's mutation status is A or B, you need to do further tests, and if it is C or D, then treat with this therapy," he explained.
The end product, Clough said, would be a "clinical decision tree based on mutation status."
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