Transgenomic announced last week it will develop and market an in vitro diagnostic test based on Key Genomics’ predictive gene-expression algorithm that is designed to gauge patient response to ovarian cancer treatments.
Under the terms of the collaboration, Charlottesville, Va.-based Key Genomics will supply Transgenomics with gene signatures generated by its COXEN, or CO-eXpression ExtrapolatioN, algorithm, which is designed to identify patients more likely to respond to platinum and paclitaxel chemotherapeutics for ovarian cancer.
Transgenomic, in turn, will validate Key Genomics’ gene signature and translate it into an in vitro diagnostic.
“The first step will be to confirm in [formalin-fixed, paraffin-embedded] tissues the positive ovarian cancer COXEN results obtained with frozen tissues. After this, there is an anticipated period of refinement of the algorithm, which will then be followed by a clinical validation study,” Eric Kaldjian, Transgenomic’s chief scientific officer, told Pharmacogenomics Reporter this week.
Transgenomic, based in Omaha, Neb., is currently studying which gene-expression technology platform will optimize performance of the COXEN signatures and plans eventually to file the resulting test with the US Food and Drug Administration as an in vitro diagnostic multivariate index assay. The company’s more immediate goal is to launch a validation trial by next year.
In order to generate its proprietary ovarian cancer drug-response gene profile signature, Key Genomics used the COXEN algorithm, which combines genomic and pharmacological response data from the National Cancer Institute’s 60 cell-line panel.
The COXEN algorithm “functions as a Rosetta Stone for translating the gene-expression signature of an ovarian-cancer specimen into a prediction for drug activity,” Kaldjian said. “COXEN-derived biomarkers contain predictive information for a patient’s response to a specific therapy.”
These gene signatures, discovered by Key Genomics, are currently being reviewed by a medical journal for publication.
Instead of relying solely on specific gene signatures, the COXEN algorithm also takes into account observed data and gene signatures that have been linked to therapeutic response, he explained.
“It is anticipated that high-sensitivity mutational analysis — a core expertise of Transgenomic based on its WAVE DHPLC and Surveyor Endonuclease technologies — can complement COXEN gene expression signatures,” Kaldjian said.
Prior to Key Genomics’ efforts in ovarian cancer drug response, researchers successfully used COXEN to predict chemotherapeutic sensitivity in bladder cancer and breast cancer.
According to Kaldjian, the COXEN signature contains between 15 and 30 novel response genes for a given ovarian cancer treatment, and these genes span a number of cellular networks, such as cell cycle, apoptosis, morphology, and metabolic pathways.
“The algorithm can compound the number of gene targets it evaluates to provide response scoring for several chemotherapy agents as is typical for most cancer therapy treatment regimens,” Kaldjian said.
These gene signatures, discovered by Key Genomics, are currently being reviewed by an undisclosed medical journal for publication, Kaldjian added.
By the time Transgenomic’s IVD comes to market in the next few years, however, there is likely to be more competition in the ovarian cancer drug-response space.
Myriad Genetics’ patents on BRCA1 and BRCA2 genes have helped make its BRACAnalysis tests the best-known products designed to gauge ovarian cancer risk. But some studies have also linked BRCA mutations to improved survival in ovarian cancer patients treated with platinum-based chemotherapy.
However, Rosetta Genomics has said that in the next two years it expects to launch an miRNA-based diagnostic that can predict response to platinum-based ovarian cancer treatments.
In addition, researchers at Berkeley Lab and the University of California, San Francisco, have identified a class of proteins that can gauge response to oxaliplatin-based anticancer treatments, and have discovered predictive markers for identifying ovarian cancer patients who will not respond to current combinations of chemotherapies.
According to the Berkeley Lab website, the researchers are currently looking for licensing and collaborative research opportunities for these technologies.
The NCI estimates that in 2008 there will be more than 21,000 new cases of ovarian cancer in the US and more than 15,000 related deaths. Transgenomic estimated that it costs the US healthcare system $2.2 billion each year to treat ovarian cancer.
A diagnostic test based on COXEN “has the potential to bring significant healthcare and economic value by personalizing cancer therapy by using such a method, an algorithm based on in vitro response to anti-cancer drugs,” Key Genomics CEO Tim Gallagher said in a statement.
Neither Transgenomic nor Key Genomics provided an estimate of potential pharmacoeconomic savings.