Genasense correlates with target and biomarker effects in cancer patients

A new clinical pharmacologic study using Genta's, Genasense (oblimersen sodium) Injection, in patients with acute myelocytic leukaemia (AML)has shown a correlation between the levels of Genasense achieved within cancer cells and a decrease in Bcl-2, the molecular target of Genasense therapy.

The investigators reported the development of a new, highly sensitive assay for Genasense that can detect very low concentrations within a cancer cell. They applied this technique to the evaluation of Genasense uptake in a human leukaemic cell line, and also in blood cells and bone marrow taken from patients with AML who were being treated with Genasense.

Results with the cell line showed that the assay successfully detected intracellular Genasense concentrations that were sufficient to down-regulate protein levels of Bcl-2. Drug levels within the cell were significantly increased using a lipid carrier. Subsequent studies were carried out using AML cells taken directly from patients undergoing Genasense treatment. These data showed that intravenous therapy with Genasense achieved intracellular concentrations that far exceeded levels that could be achieved in the cell line without using a carrier, and which were sufficient to down-regulate Bcl-2.

The new report parallels data from a recent study in 20 patients with hormone-refractory prostate cancer who were treated with Genasense plus docetaxel (Taxotere; sanofi aventis).

In this Phase I study, seven of 12 patients who had not previously received a taxane showed a decrease in prostate specific antigen (PSA), a marker of prostate cancer activity. The median PSA decrease in responding patients was 78% (range, 52% to 99%). Measurement of Bcl-2 content within 17 samples of primary tumour biopsies were scored as weak (1+), intermediate (2+) or strong (3+), and clinical responses were observed in patients from all 3 categories. Bcl-2 was also measured in blood cells taken from four patients, and decreases ranging from 92% to 98% of baseline levels were observed after Genasense treatment. Lastly, one patient who underwent serial biopsies of metastatic prostate cancer showed a 40% decrease of Bcl-2 in tumor tissue on day six of Genasense therapy.

About Genasense

Genasense inhibits production of Bcl-2, a protein made by cancer cells that is thought to block chemotherapy-induced apoptosis (programmed cell death). By reducing the amount of Bcl-2 in cancer cells, Genasense may enhance the effectiveness of current anticancer treatment. Genta is pursuing a broad clinical development program with Genasense evaluating its potential to treat various forms of cancer.