This article has been updated from a previous version to include additional comments from Insight Genetics.
By Ben Butkus
Molecular diagnostics firm Insight Genetics said last week that it has inked an exclusive worldwide licensing agreement with St. Jude Children's Research Hospital for mutations in the anaplastic lymphoma kinase gene that confer resistance to ALK inhibitors.
Insight said it will use the license to develop a pair of real-time PCR-based tests intended to help physicians monitor cancer patients for mutations and upregulation in the ALK gene in order to make more effective treatment decisions.
The company is developing its tests using TaqMan probes on Life Technologies' ABI 7500 Fast Dx real-time PCR system, Josh Nickols, Insight's vice president of research and development and chief technology officer, told PCR Insider this week.
"We are conducting allele-specific PCR," Nickols said. "In the past we have used microarrays to develop molecular tests, but found that they do not offer the sensitivity and resolution that real-time PCR does."
As part of the agreement, Nashville, Tenn.-based Insight is collaborating with the laboratory of St. Jude's Stephan Morris, who discovered the ALK oncogene and mutations conferring resistance to ALK inhibitors.
According to Insight, ALK has been identified as a cause of a number of cancers, including non-small cell lung cancer, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma. As such, several pharmaceutical companies, including Pfizer and Roche subsidiary Chugai, and Exelixis, are developing ALK inhibitors to treat ALK-positive tumors.
However, over time patients can develop resistance to ALK inhibitors, Insight said. The company's license with St. Jude covers a number of mutations that can spontaneously arise following treatment.
Specifically, Insight is developing a test called ALK Resistance, which will provide physicians with real-time information about the mutation status of ALK in several cancers and help guide prescription of alternate treatments; and ALK Screen, which will allow healthcare providers to detect the presence of any cancer-causing ALK fusion mutation as well as wild-type ALK upregulation.
"Clinical studies have shown that cancers caused by ALK mutations are very sensitive to ALK inhibitor therapies whereas cancers caused by non-ALK mechanisms exhibit little or no antitumor responsiveness," St. Jude's Morris said in a statement. "It is essential that patients be tested at diagnosis and monitored subsequently with respect to the ALK mutational status of their cancers."
Last month, Insight said that it won a $200,000 Phase I Small Business Innovation Research grant from the National Cancer Institute to develop a lung cancer-specific PCR-based ALK Screen test, also in collaboration with St. Jude. According to Insight, 5 to 10 percent of lung cancers are caused by ALK mutations.
"Non-small cell lung cancer is certainly the first malignancy for which we expect Insight ALK Screen will prove important," Nickols said, adding that neuroblastoma, certain lymphomas, and inflammatory myofibroblastic tumors are also known to arise from ALK mutations.
"There is some evidence in published scientific literature that ALK mutations may be involved in breast cancer and colorectal cancer, and if this proves true, we believe Insight ALK Screen will become an important diagnostic tool for these cancers too," Nickols added.
Life Tech's ABI 7500 Fast Dx platform earlier this year received the CE Mark for in vitro diagnostic use in Europe (PCR Insider, 3/25/10); and in 2008 received 510(k) clearance from the US Food and Drug Administration to perform the US Centers for Disease Control's influenza virus panel test.
Since that time, Life Tech and other companies received 510(k) approval for H1N1 flu tests on the 7500 Fast Dx under the Emergency Use Authorization program, but those clearances have since expired, a Life Tech spokesperson said.
As such, companies wishing to develop IVD tests on the 7500 Fast Dx in either the US or countries recognizing the CE IVD Mark would only need to seek regulatory approval for its ALK molecular tests for use on that system. In addition, they would need to contact Life Technologies regarding intellectual property rights.
It is unclear whether Insight has begun that process. In the short term, however, "we are just developing this as a research-only test," Insight's Nickols said. In fact, ALK Screen is already available as an RUO test, the company said.
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