Trovagene announced last month that it has granted Novartis' diagnostics laboratory, Genoptix, a worldwide, non-exclusive license to incorporate the nucleophosmin protein marker into research and clinical testing services for acute myelogenous leukemia.
According to Trovagene, the terms of the agreement include both upfront fees and royalties. Detailed financial terms were not disclosed.
Several other companies have negotiated licenses from Trovagene to offer NPM1 mutation testing as a clinical service for diagnosis and monitoring of patients with AML, including Duke University, Quest Diagnostics, Laboratory Corporation of America, Fairview Health Services, and Invivoscribe Technologies.
Testing for NPM1 mutations is recommended by the National Comprehensive Cancer Network, due to its association with disease progression and severity.
Genoptix's parent company Novartis is developing an investigational AML drug, midostaurin, which is currently in Phase III clinical trials as a treatment for newly diagnosed patients with FLT3 mutations. Novartis has contracted Invivoscribe, which also holds a license for NPM1 mutation testing from Trovagene, to develop a companion FLT3 test for the drug (PGx 2/23/2011).
At the time, Invivoscribe CEO Jeffrey Miller said that it remained to be seen whether Novartis and Invivoscribe would develop companion diagnostics for mutations other than FLT3, but added that physicians treating AML patients routinely request testing from the company for both FLT3 and NPM1 mutations.
According to a review by researchers at the University Hospital of Ulm in Germany, NPM1 mutations have been found to "cooperate" with other gene mutations in leukemogenesis. "Approximately 40 percent of patients with NPM1 mutations also carry FLT3 internal tandem duplications," the authors wrote, while several studies have "unanimously showed that the genotype mutant NPM1 without FLT3-ITD represents a favorable prognostic marker."
Accumulating evidence suggests that FLT3 and NPM1 genotypes together can be used to assess the disease outcomes of AML patients. For example, there is data suggesting that patients with NPM1 mutations and wild type FLT3 have a more favorable risk status, those with FLT3 mutations and mutated NPM1 fall in the middle, and those with FLT3 mutations in the absence of NPM1 mutation may have the worst prognosis.
It is unclear how Genoptix specifically plans to use its license for the NPM1 marker. Genoptix declined to comment on whether it plans to test patients in ongoing studies of midostaurin for NPM1 mutations, or provide details on how it plans to use the NPM1 marker in any other way.
According to the NCCN, NPM1 has also shown promise in several studies as a tool to track minimal residual disease in AML, and NPM1 mutations are more stable than FLT3 aberrations, making them potentially more suitable for monitoring MRD.