New Results Show Clinical Activity of Genasense in
Combination with Chemotherapy in Previously Untreated Patients
with Acute Myeloid Leukemia
PHILADELPHIA, December 9, 2002 --
Genta Incorporated (Nasdaq:
GNTA
-
News
) announced the presentation of two studies that extended the
activity of Genasense(TM) in acute myeloid leukemia (AML). Results
were presented on Saturday at the 44th annual meeting of the
American Society of Hematology (ASH) in Philadelphia, PA.
The first study was presented by investigators from
the University of Pennsylvania who are conducting the recently
initiated clinical study of Genasense in children with advanced
cancer. A particularly lethal form of leukemia in small children is
characterized by a specific genetic abnormality, the MLL
translocation. In the current preclinical study, investigators
showed that Genasense down-regulated the Bcl-2 protein in MLL
leukemia cells by approximately 60%, and that the drug directly
killed the leukemia cells.
The second study reported preliminary clinical
results from an ongoing Phase 1 study testing Genasense in
combination with increasing doses of two standard chemotherapy
drugs (daunorubicin and cytosine arabinoside [ARA-C]) in the
so-called "7 and 3" regimen. Patients were eligible for the study
if they were older than 60 years of age and had not previously
received chemotherapy. Many of these patients had pre-existing
blood diseases, multiple genetic abnormalities, and a variety of
other medical complications, all of which have are known to
contribute to poor outcomes with standard chemotherapy.
To date, the combined Genasense/chemotherapy
program has not caused more side-effects than expected from using
chemotherapy alone, which is a critical factor for this group of
patients. Overall, 5 of the first 11 evaluable patients have
achieved complete remission (CR); accrual of additional patients is
continuing at higher dose levels. Genasense was shown to decrease
the expression of Bcl-2 protein in blood cells, especially when
these cells were segregated between leukemic and normal cell
populations prior to analysis. This trial, which was conducted at
Ohio State University and the University of Chicago, was sponsored
by the U.S. National Cancer Institute (NCI), pursuant to Genta"s
Cooperative Research and Development Agreement (CRADA) with the
NCI.
"This trial was designed as a preliminary lead-in
study conducted to evaluate safety and biokinetics of Bcl-2 as a
lead-in to a larger trial", said Dr. Guido Marcucci, Assistant
Professor at the Ohio State University School of Medicine. "These
new data provide strong support for further testing of this program
in a randomized controlled trial in newly diagnosed patients."
"These studies significantly expand our existing
programs in AML," said Dr. Loretta M. Itri, Genta"s Executive
Vice-President for Medical Affairs. "Initial clinical work from
Ohio State first established the safety of Genasense in combination
with fludarabine and ARA-C. That early study showed a 50% CR rate
in heavily pre-treated AML patients who were treated at the highest
dose levels. Based on the current data, we have indicated our
intent to support Dr. Marcucci"s new proposal to further evaluate
the "7 and 3" chemotherapy program within the NCI cooperative group
mechanism."
About AML
Acute myeloid leukemia (AML) is a rapidly
progressive cancer of the blood that is characterized by the
uncontrolled proliferation of immature white blood cells, called
blasts. The overproduction of these cells crowds the bone marrow,
radically reducing the body"s ability to form other normal and
necessary blood cells. Remission rates in adult AML are inversely
related to age, and substantially lower remission rates are
observed in older patients. In clinical studies of AML, Bcl-2
expression in leukemia cells has been correlated with significantly
poorer survival.
