Two Presentations at ASH Meeting Support Activity of
Genasense in Plasma Cell Cancers
Philadelphia, PA, December 10, 2002
- Genta Incorporated (Nasdaq: GNTA) in collaboration with Aventis
(NYSE: AVE), announced the presentation of two studies that support
the activity of GenasenseTM in two types of plasma cell cancers
known as multiple myeloma and Waldenstrom's macroglobulinemia.
These results were presented on Monday at the 44th annual meeting
of the American Society of Hematology (ASH) in Philadelphia,
PA.
The first study reported preliminary results using
Genasense in combination with a standard chemotherapy regimen
called "VAD" (which consists of vincristine, adriamycin and
high-dose dexamethasone). A key component of this trial was that
eligible patients had to have already received and progressed on
VAD therapy. Therefore, this study represented a "resistance
reversal" approach. To date, 5 patients are fully evaluable; all 5
had failed VAD, plus high-dose chemotherapy and a stem cell
transplant, and 4 of the 5 had also progressed on thalidomide.
Despite this extensive pre-treatment, 3 of the 5 patients achieved
a partial response with Genasense/VAD. The median duration of
response currently exceeds 6 months. One additional patient
achieved stabilization of disease. Serial measurements showed that
Bcl-2 protein (i.e., the target of Genasense therapy) was decreased
in patients' blood cells. Other than fatigue, side-effects did not
appear different from those expected from VAD chemotherapy
alone.
In a second preclinical study, Genasense was
evaluated in experiments using human cells of Waldenstrom's
macroglobulinemia (WM), a disease that is similar to myeloma.
Genasense used alone decreased Bcl-2 protein within these cells,
which was correlated with an increase in cell death (apoptosis).
Moreover, Genasense also amplified the killing of WM cells when
used in combination with rituximab (RituxanÆÊ; IDEC/Genentech),
fludarabine, and dexamethasone. Maximal cell death with these
combinations also correlated with the time that Bcl-2 was maximally
decreased.
"Together, these studies provide several important
insights," commented Dr. Raymond P. Warrell, Jr. MD, Genta's Chief
Executive Officer, who noted: "First, the most active component of
VAD is now felt to be high-dose dexamethasone. While we have not
focused on "resistance reversal" strategies as a registration
strategy, these early clinical data clearly suggest that
dexamethasone resistance can be modified by Genasense. Thus, these
results directly support our Phase 3 trial of Genasense with
high-dose dexamethasone in myeloma that should complete its target
enrollment this month. Second, earlier this year we initiated new
clinical trials using Genasense plus Rituxan, and - together with
the National Cancer Institute - we are planning to initiate a new
clinical trial in patients with Waldenstrom's. Lastly, fludarabine
is a key component of our ongoing Phase 3 trial in CLL. Thus, the
further documentation of Bcl-2 down-regulation in lymphoid cells,
which synergistically increases the cytotoxicity of fludarabine, is
further evidence of the contribution that Genasense may make to
enhancing the effectiveness of current anticancer therapy."
About Multiple Myeloma and Waldenstrom's
Macroglobulinemia
Multiple myeloma and Waldenstrom's
macroglobulinemia are cancers that arise in blood cells (called
plasma cells) that normally reside in the bone marrow. Plasma cells
are important because they normally produce antibodies that fight
off infections. When cancer develops in plasma cells, these cells
markedly increase in number, which can cause severe bone pain and
fractures; however, their ability to produce antibodies is actually
greatly reduced. Therefore, people with these conditions are highly
susceptible to infections. Malignant plasma cells are known to
contain a high amount of Bcl-2 protein, which is targeted by
Genasense. Further information about these diseases can be found at
the website of the Multiple Myeloma Research Foundation:
http://206.204.218.38/default.asp
.
About Genasense
GenasenseTM works by inhibiting the production of
Bcl-2, a protein made by cancer cells that is thought to block
chemotherapy-induced cell death. By reducing the amount of Bcl-2 in
cancer cells, Genasense may enhance the effectiveness of current
anticancer treatments. Genasense is currently in multiple,
late-stage, randomized clinical trials in patients with malignant
melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL) and
non-small cell lung cancer.
