Almac Diagnostics, a Craigavon, UK-based diagnostic developer, has partnered with Cancer Research UK to develop a gene expression signature that the company hopes will aid clinicians in treating patients with early-stage breast cancer, according to an Almac official.
Richard Kennedy, the firm’s vice president of clinical diagnostics, told BioArray News last week that Almac will be using its research-use-only Breast Cancer Disease-Specific Array to screen breast cancer tissue samples. The goal of the project will be to develop a gene expression signature that can be used to identify patients that are at greater risk of a recurrence of ductal carcinoma in situ following surgery.
DCIS occurs when pre-cancer cells grow in the milk duct of the breast, and have the possibility to spread to other parts of the breast. Sometimes DCIS does not return after removal from the milk duct. Other times, though, it can recur and cause more serious forms of breast cancer, Kennedy said. A DCIS diagnostic, therefore, would be able to guide treatment by allowing patients that are not at risk of recurrence to avoid unnecessary procedures like radiotherapy, while enabling greater confidence in decisions taken to treat patients that are at greater risk of DCIS recurrence, he said.
“At the moment one in five positive mammograms has DCIS only,” said Kennedy. “The problem is to date no physician has a way of predicting which of these DCIS patients develop breast cancer,” he said. “When you remove DCIS, 30 percent will recur [and] 70 percent will not come back again. The aim is to determine which of the 30 percent will see the disease come back because they are the population that needs more treatment beyond having the disease removed.”
Almac already has an ongoing collaboration with Massachusetts General Hospital in Boston and others to develop a diagnostic for colorectal cancer patients with the goal of seeking US Food and Drug Administration 510 (k) clearance, perhaps as early as next year. According to Kennedy, Almac has similar intentions for the results of its breast cancer work with Cancer Research UK. Both tests, should they reach the market, will be manufactured by Affymetrix to run on its platform.
In the Cancer Research UK collaboration, Almac is working with Adrian Harris, a Cancer Research UK researcher and a professor of medical oncology at the University of Oxford. The first phase of the project will be a pilot study of 50 formalin-fixed, paraffin-embedded samples from tissue archives.
“We’ll have 25 samples where the [DCIS] did recur in five years, and 25 in which the disease did not recur after eight years,” explained Kennedy. He said that Almac is not looking for any particular set of markers, though its Breast Cancer DSA has been designed to comb through FFPE samples, which are notoriously difficult to work with but form the bulk of cancer tissue archives available to researchers.
“This particular array was developed specifically for extracting information from FFPE tissue, especially breast cancer tissue,” Kennedy said of the DSA. “This has been developed for genes specific to breast cancer,” he said.
The number of markers that will wind up in an eventual test “depends on the kind of data we see,” he added. “Ideally we would like a simple profile, but it needs to be robust and it really depends on the amount of difference we are seeing in the signature.”
If the collaboration with Harris’ lab does yield a robust signature, Kennedy said that Almac will look for larger partners for the clinical studies necessary to support a 510 (k) submission. “We will approach groups to run a larger study to validate the signature on our array,” he said. According to Kennedy, future studies will also be retrospective and use archival tissue, like the work with Harris.
Even as Almac moves forward, Oxford will still continue to benefit from the work, he said. “The deal with Oxford is that the commercialization of the signature would belong to Almac,” Kennedy explained. “The papers, research, and information though would belong to Oxford University,” he added.
In May, Almac disclosed that it is in preliminary discussions with the FDA about submitting a test for colorectal cancer recurrence sometime next year. Like its Breast Cancer DSA, Almac developed its prognostic gene signature for colorectal cancer test entirely from formalin-fixed, paraffin-embedded samples. It is designed to help clinicians determine the risk of cancer recurrence in patients diagnosed with stage II colorectal cancer (see BAN 5/29/2007).
"We hope, subject to further FDA discussions, to submit the CRC Stage II test for clearance sometime in 2008," Almac CEO and co-founder Paul Harkin wrote to BioArray News at the time. "However the timeframe will depend entirely on clinical study design, which we hope to agree with FDA in the coming months. There can be no assurance that the product will be cleared in 2008," he added.
“Ideally we would like a simple profile, but it needs to be robust and it really depends on the amount of difference we are seeing in the signature.”
Last week, Kennedy said that Almac is in the “final phases of verifying the study in larger retrospective studies.” He added that Almac will probably approach the FDA about the test again sometime next year. “We are at the stage where we need a larger data set for approval, so we are looking at that for the moment with Mass General and others,” he said.
In April, Almac said that it was working with Massachusetts General Hospital to screen colorectal polyp tissue samples in an effort to develop a signature that could help physicians diagnose early-stage colorectal cancer (see BAN 4/10/2007).
Besides the colorectal and breast cancer work, Almac also has the potential to turn more of its disease-specific arrays into diagnostic discovery tools. The firm has plans to introduce DSAs for lung cancer, prostate cancer, and ovarian cancer over the next few months, with the Lung Cancer DSA penciled in for a launch sometime in September or October.
Kennedy said that it is likely that once these arrays are introduced, Almac will seek similar partnerships like the one with Cancer Research UK and Oxford University to track down diagnostic-worthy gene signatures.
“At present we are developing other DSAs and we would plan similar studies in the future,” he said. “At the moment we are talking to various researchers about similar studies with these arrays that are being completed,” he added.
All arrays have been manufactured through an OEM deal with Affymetrix, said Kennedy. Almac Diagnostics signed a diagnostics development agreement to create tests for use on the array vendor’s platform in 2005 when it was known by its previous name, ArraDx (see BAN 10/26/2005).