“The role of companion diagnostics is changing,” says Walter P. Carney, Ph.D., Siemens Medical Solutions Diagnostics (www.medical.siemens.com). “Several large pharmaceutical companies are already exhibiting forward thinking toward development of companion diagnostic products. The blockbuster drug model is slowly giving way to more targeted therapeutic options.
“The clinical failure of AstraZeneca’s (www.astrazeneca.com) Iressa®, indicated for the treatment of patients with advanced or metastatic non-small cell lung cancer, was perhaps a major wake-up call. A specific biomarker would increase the success of a drug like Iressa by selecting a smaller population with a higher response to the drug.”
Iressa targets epidermal growth factor (EGFR) in cancer cells. EGFR is a membrane-bound protein; its extracellular domain is shed from the surface of normal and cancer cells and can be detected in blood. Siemens Medical Solutions Diagnostics has developed an FDA-cleared test for the circulating oncoprotein HER-2/neu as well as a research-use only ELISA assay to measure circulating EGFR levels in clinical samples. Changes in serum levels of HER-2/neu or EGFR correlate with disease progression, and thus could be clinically useful in deciding on the course of therapy.
Siemens reports that it is also the first company to introduce a research-use ELISA assay for the circulating extracellular domain of carbonic anhydrase IX (CAIX), a biomarker of hypoxia.
“This biomarker can be measured by immunohistochemistry, ELISA, and imaging, thus presenting opportunities for continuous diagnostics throughout the course of the disease,” continues Dr. Carney. “Changes in CAIX circulating levels, as detected by ELISA, would indicate whether the tumor growth is recurring after the initial biopsy. The goal is to intervene at the earliest possible time and provide patients with a targeted treatment, such as Rencarex®.
Rencarex, a CAIX-specific antibody developed by Wilex (www.wilex.com), is currently in Phase III trials for treatment of nonmetastatic renal cell carcinoma. CAIX ELISA could also assist in predicting therapy outcome and in monitoring efficacy of Rencarex-mediated treatment.
Wilex has an imaging-diagnostic agreement with the nuclear medicine service department of Memorial Sloan Kettering Cancer Center. In the collaboration, G250, a CAIX-specific antibody conjugated with a contrast agent, is injected into renal cell carcinoma (RCC) patients and accumulation of the radioactive label is monitored by PET/CT imaging. The initial studies demonstrated a high degree of correlation between the label accumulation and RCC diagnosis.
“Targeted therapies are the way of the future. They result in fewer side effects and higher efficacy,” adds Dr. Carney.
“The advances in this space go hand-in-hand with the development of companion diagnostics, and circulating biomarkers fit perfectly with our vision at Siemens of combining circulating biomarkers (DNA, RNA, proteins or autoantibodies) with in vivo imaging. Circulating biomarkers provide real-time information about disease progression, and at some point our biomarker-based tests will be sensitive enough to deliver a long-term prognosis.”