PGxHealth, a division of Clinical Data, Inc has established a research collaboration with Antonino Musolino, and the Azienda Ospedaliero - Universitaria di Parma (University Hospital of Parma), Italy, to validate the use of geneticvariants in the FCGR pathways in predicting response to trastuzumab (Herceptin) therapy in patients with breast cancer. The research will include an international prospective trial to evaluate the association of genetic variants, such as the FCGR3A F158V genotype, with response to trastuzumab in breast cancer treatment. The collaboration expands PGxHealth's FCGR (Fc gamma receptor) program that includes its PGxPredict: Rituximab test for a gene variant used to determine response to rituximab monotherapy in follicular non-Hodgkin's lymphoma.

"In our pilot study, Fc gamma receptor genetic variants were strong predictors of trastuzumab efficacy in HER-2 positive metastatic breast cancer patients," said Antonino Musolino, Medical Oncology Unit, University Hospital of Parma. "Combining our efforts with PGxHealth's to confirm this result is an important step forward in optimizing breast cancer treatment and may lead to a fully validated pharmacogenetic test for targeted therapy in solid tumours."

PGxHealth scientists will collaborate with Dr Musolino and his colleagues to analyze certain genetic variants in patients enrolled in an international trial of approximately 300 breast cancer patients receiving trastuzumab along with other drugs in the neoadjuvant setting (before primary treatment), to determine whether the FCGR3A F158V and other variants are predictive of clinical outcome. This study is expected to be completed by the end of 2009.

"Clinical evidence demonstrating the importance of FCGR variants in predicting the efficacy of monoclonal antibody-based cancer therapies continues to grow, and augments our own efforts related to IgG1 antibody response," said Carol R Reed, chief medical officer of Clinical Data. "By establishing collaborations with world-renowned oncology researchers, such as Dr Musolino, we are aiding the development of genetic tests that can predict drug response and help guide treatment decisions for clinicians and their patients with cancer."

The importance of genetic variation in the FCGR3A pathway is gaining attention among researchers and clinicians, and will also be highlighted in a poster session at the 31st Annual San Antonio Breast Cancer Symposium on December 14, 2008, Poster Session VI: Prognosis and Response Predictions: Response Predictions - Biomarkers and Other Factors. The impact of the FCGR3A pathway for optimizing treatment of lymphomas, breast, and colorectal cancers with rituximab, trastuzumab and cetuximab and other recombinant mAbs was the focus of the MAb IMPACT meeting of oncology experts, held in November 2008 in Tours, France.

FCGR3A, a gene that encodes an Fc gamma receptor, binds both natural and therapeutic IgG antibodies. The FCGR3A receptor transmits signals from the membrane into the cell via tyrosine kinase activity. This signalling pathway is important in regulating antibody-dependent cellular cytotoxicity (ADCC), a mechanism that is important to the efficacy of many monoclonal antibody-based (mAbs) therapies. Recent studies have suggested that genotyping FGCR3A and other Fc gamma receptors may be important in predicting response to cetuximab in colorectal cancer and to trastuzumab in breast cancer.

PGxHealth's PGxPredict: Rituximab test detects a single nucleotide polymorphism in FCGR3A that has been found to independently predict the response of patients with follicular non-Hodgkin's lymphoma to treatment with rituximab monotherapy.

PGxHealth has extensive experience and capabilities in the development, clinical validation and delivery of genomics-based tests.