Abbott Molecular has filed premarket approval applications with US and Japanese regulatory authorities for a molecular diagnostic test that will help personalize treatment with Pfizer's non-small-cell lung cancer drug crizotinib.
According to a statement from Abbott, the company is seeking approval from the US Food and Drug Administration and the Japanese Ministry of Health, Labor, and Welfare for a new molecular diagnostic test designed to detect abnormal gene rearrangements in NSCLC tumors. The announcement comes one week after Pfizer said it had filed regulatory approval applications for the NSCLC ALK inhibitor crizotinib in the same countries (PGx Reporter 05/18/2010).
In clinical trials crizotinib has shown efficacy in advanced NSCLC patients whose tumors harbor EML4 and ALK fusion transcripts. Pfizer is working with Abbott to pick out patients most likely to respond to crizotinib in clinical trials, and the companies have an arrangement to simultaneously launch the drug and test commercially in various US and overseas locales.
Pfizer and Abbott had previously said they intended to file their marketing applications for the drug and the test around the same time to ensure that once the drug is launched in the market, its companion test would also be available (PGx Reporter 01/19/2011).
The companion test developed by Abbott is based on fluorescence in situ hybridization technology and detects rearrangements of the 2p23 chromosome of the ALK gene, which have been found to contribute to the development of NSCLC, lymphoma, and neuroblastoma, the company said.
"As more is learned about cancer and tumor formation, genetic biomarker identification will become an increasingly valuable protocol governing the use of new personalized medications," Stafford O’Kelly, head of Abbott’s molecular diagnostics business, said in a statement. "The Abbott ALK FISH test is designed to help physicians select appropriate patients with non-small-cell lung cancer for targeted drug treatment. It is the only test being used in multi-center global clinical trials in conjunction with Pfizer’s crizotinib."
The FDA has granted crizotinib's application Fast Track status and priority review, placing it on a six-month review clock. Pfizer also received orphan drug status for crizotinib, since the drug will be indicated for a small subset of the NSCLC population. The National Cancer Institute reported that there were 222,520 newly diagnosed cases of NSCLC last year, and 157,300 deaths from the disease. It is estimated that between three percent and five percent of NSCLC tumors are ALK-positive.
In Japan, Pfizer commenced crizotinib clinical trials in March 2010, and Japanese health regulators also granted the drug orphan drug status in January 2011. The presence of the ALK fusion gene in lung tumors was first reported by researchers from Jichi Medical University, University of Tokyo, Japanese Foundation for Cancer Research, and the Japan Science and Technology Agency in 2007. Studies suggest that crizotinib's inhibitory activity against ALK cuts off cell signaling pathways that tumor cells depend on for growth and survival.