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Almac's Ovarian Cancer Patient Stratification Test Could Be Used to Select Treatment for Other Diseases

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NEW YORK (GenomeWeb) — Almac Diagnostics has developed a microarray-based test that can be used to determine which ovarian cancer patients will have a good prognosis following chemotherapy.

The company is currently validating the test, which is run on the Affymetrix platform, with the intention of making it available for clinical use next year. Almac also believes the assay could be used to stratify patients suffering from other cancers who have undergone chemotherapy, according to Richard Kennedy, the firm's medical director.

"The discovery was made in high-grade serous ovarian cancer but we believe it will hold up in other disease indications as it represents a fundamental biology," Kennedy told BioArray News this week. "Some of our initial studies have confirmed this."

Almac Diagnostics is a business unit of the Almac Group, a Craigavon, UK-based contract research organization. To further its own research and its partners' efforts, the company has developed a menu of Disease Specific Arrays, or DSAs, for breast, ovarian, colorectal, lung, and prostate cancer. Each of these Affymetrix-manufactured chips contains about 60,000 transcripts associated with a particular disease. The firm has also developed a more generic, cancer-focused array called Xcel that Affymetrix distributes globally as a catalog chip.

Almac used its Ovarian DSA to develop and validate its new assay for ovarian cancer patient stratification. The 63-gene test, called ALM AADx, relies on an expression signature to identify a subgroup of high-grade serous ovarian cancer patients that have a good prognosis following standard-of-care chemotherapy.

"We believe that this is the first assay that has identified a group of patient that could be harmed by the addition of Avastin to standard therapy," said Kennedy.

This "good prognosis" subgroup demonstrated worse progression-free and overall survival following the administering of bevacizumab within the ICON7 translational dataset, while patients whose tumors fell outside of this molecular subgroup tended toward improved, progression-free survival when given the compound, Kennedy said. Bevacizumab is an angiogenesis inhibitor that Roche markets under the name Avastin. It is used to treat various cancers worldwide, including kidney, lung, and colorectal.

While Avastin is licensed as a first-line therapy for ovarian cancer, it is not considered a first-line therapy for US ovarian cancer patients. The majority of clinicians, however, do prescribe Avastin for this indication in the US, based on a modest progression-free survival advantage in several clinical studies, Kennedy noted.

The molecular subgroup that the test identifies is defined by the absence of angiogenesis and represents around 40 percent of the HGSOC population. Almac and collaborators at the University of Edinburgh previously discussed their discovery of the subgroup at the American Society of Clinical Oncology three years ago. During the society's annual meeting last month, Almac and partners demonstrated the validation of the new stratification assay in the Medical Research Council UK's ICON7 dataset.

In total, Almac identified three molecular subgroups within HGSOC: an immune subgroup with angiogenic gene inactivation and immune gene upregulation that has better overall survival rates; and two with angiogenic gene upregulation and worse survival rates following first-line chemotherapy. The firm is now looking to further validate its results as well as explore the use of its assay in other cancers.

"The assay identifies ovarian cancer patients who do well with standard chemotherapy but may exhibit worse progression-free and overall survival following the addition of Avastin," said Kennedy. "The same molecular subtypes based on angiogenesis are present in colon, breast, and lung cancer and we are planning to validate the assay as a predictor of response to anti-angiogenic therapies in these settings," he said. As the company believes that the assay represents the fundamental biology underlying angiogenesis, it could be applicable to other anti-angiogenesis agents such as receptor tyrosine kinase inhibitors, according to Kennedy.

Given the success of Almac's work so far, Kennedy said the company is working toward the goal of making the test available clinically next year as it investigates its broader application.

According to Kennedy, Almac has met with the US Food and Drug Administration regarding the assay, and is planning to obtain CE-IVD marking for its test in Europe. He said that it is the firm's intention to make the assay available as a laboratory-developed test via its clinical laboratories in Craigavon and Durham, NC, in 2015. Kennedy added that Almac will continue to work with the FDA to gain regulatory approval for its test as a service lab-delivered assay. The company has no plans to make it available as a catalog, kitted product that can be run in other labs, he said.

Almac has recently moved closer to marketing a number of internally developed tests. In January, it announced that its partner Precision Therapeutics had validated ColDx, Almac's array-based, 634-gene-signature test for stage II colorectal cancer recurrence, ahead of a planned US launch. Almac has also licensed a 44-gene-signature test for breast cancer chemotherapy response to Genomic Health. Genomic Health plans to make the test available using quantitative PCR.

According to Kennedy, the size of the new 63-gene-signature ovarian cancer test "would be amenable to migration to qPCR." Still, as the assay was discovered and validated using the Ovarian DSA, the company has no current plans to move it off of the microarray platform, he said.

A number of other companies with microarray and multiplexing technology platforms have shown interest in launching tests to determine who will respond best to various ovarian cancer treatments.

Earlier this year, HTG Molecular Diagnostics announced that Ovagene Oncology would migrate some of its tests for gynecological cancers, including an assay that gauges patient response to various therapies, to HTG's Edge system.

And Toronto-based Axela announced a similar partnership in 2012 with Ovagene Oncology to develop a pharmacogenomic test for ovarian cancer.

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