LUGANO, SWITZERLAND, June 4, 2008 Finbarr Cotter, M.D., Ph.D., Professor of the Institute of Cell and Molecular Science at Barts and The London School of Medicine, today presented in an oral session "Clinical Caspase Activation in CLL by GCS-100: a Phase 2 Study" at the 10th International Conference on Malignant Lymphoma (10-ICML). The promising interim results from this ongoing clinical trial indicate that single-agent GCS-100 induces apoptosis (programmed cell death) in patients' CLL cells, reduces leukocyte count in some patients and is generally well tolerated. GCS-100 targets galectin-3, a protein over-expressed in cancer cells that promotes their survival, proliferation and metastasis.
The ongoing Phase 2 single-arm study of GCS-100 given intravenously as a single agent to relapsed CLL patients is designed to evaluate the effects of GCS-100 on various markers of apoptosis and to assess clinical activity and safety. Patients enrolled have had between one and two prior therapy regimens, which included chlorambucil, fludarabine, cyclophosphamide, and rituximab in combination or as a single agent. Of the nine patients enrolled to-date, six are evaluable for biological marker activity and five are evaluable for clinical activity.
The primary objective of the study is to evaluate the effect of GCS-100 on biomarkers of apoptosis in patients' CLL cells. Caspases -8 and -9 were activated in the CLL cells from all six evaluable patients, as measured by western blot analysis. DNA fragmentation in patients' CLL cells also was observed, strengthening the evidence that GCS-100 induces apoptosis.
The secondary objective of the study is to evaluate the effect of GCS-100 on peripheral blood leukocyte counts, which are aberrantly elevated in CLL patients. Of the five evaluable patients, two had significant reductions in leukocyte counts compared with baseline levels, including one with a 76% reduction and another with a 42% reduction and a reduction in lymph node size.
GCS-100 was generally well tolerated in the nine patients treated to-date. None of the patients had myelotoxicities, such as neutropenia, lymphopenia or thrombocytopenia, associated with GCS-100. The most common adverse event was rash, which was generally self-limiting and mild-to-moderate in severity. One patient experienced a grade 3 adverse event (indigestion and epigastric pain) and ended treatment. One patient died of pneumonia unrelated to GCS-100.
"These signals of biologic and clinical activity were without signs of overlapping toxicities, such as myelotoxicity, found in current therapies for CLL," said Dr. Cotter. "These early data are particularly encouraging given that relapsed patients, especially those previously treated with standard agents such as fludarabine and rituximab, are difficult to treat."
Based on these results and encouraging preclinical evidence of synergy of GCS-100 with cytotoxic agents, Prospect Therapeutics is planning to initiate a clinical trial of GCS-100 combined with chemotherapy in CLL patients following the completion of this single-agent trial.
GCS-100 is a proprietary polysaccharide that targets galectin-3. Galectin-3 is a protein over-expressed in cancer cells that promotes their survival, proliferation and metastasis. Galectin-3 is part of a family of proteins that bind to carbohydrates and is found in high concentrations in many human cancerous tumors, including chronic lymphocytic leukemia, multiple myeloma and lymphoma.
CLL, a blood-borne cancer, is the most common form of adult leukemia worldwide. CLL is characterized by proliferation of malignant white blood cells, referred to as lymphocytes, in the bone marrow, lymph nodes and spleen, which leads to an increase in white blood cell counts as well as enlarged lymph nodes and spleens in most patients. The disease is progressive and often fatal with a five year survival rate of 75%. According to The Leukemia & Lymphoma Society, approximately 95,000 patients have CLL in the United States, and there were approximately 15,300 new cases of CLL diagnosed in the United States in 2007.
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