Catumaxomab, Representing a New Generation of Antibodies, Proved Efficient and Safe in Malignant Ascites
31/05/2008 20:01
PR Newswire
MUNICH, Germany and CHICAGO, May 31 /PRNewswire/ --
- Data presented at 44th Annual ASCO Congress, Chicago, USA
Treatment with the trifunctional antibody catumaxomab
significantly prolongs puncture-free survival in patients with malignant
ascites, according to the results from a Phase II/III trial presented at the
44th American Society of Clinical Oncology (ASCO) congress. The prolonged
time to next therapeutic puncture and reduced ascites signs and symptoms
emphasize the clinical relevance of catumaxomab treatment. In addition,
catumaxomab administered to patients of the control arm after study end
showed a clear improvement in time to next puncture. Overall survival data
indicate a survival benefit. Catumaxomab represents a new generation of
antibodies in the field of oncology. A new drug application was submitted to
EMEA in December 2007 for catumaxomab for the indication malignant ascites
due to epithelial tumors (carcinomas).
"The development of trifunctional antibodies represents a new
targeted therapy for treatment of tumors, and these results provide clear
evidence for efficacy and safety of catumaxomab in the management of
malignant ascites, one of the conditions being investigated with a
trifunctional antibody," said lead investigator Simon L. Parsons, Nottingham
City Hospital, UK, at the presentation of the trial results in Chicago.
The study involved 258 patients with malignant ascites due to
epithelial tumors (carcinomas). Of those, 129 suffered from ovarian cancer
while another 129 had non-ovarian cancers. Patients received either puncture
(paracentesis) and four intraperitoneal infusions of catumaxomab within 11
days, or paracentesis alone (control group).
The trial met its primary endpoint with high statistical
significance. Patients treated with catumaxomab showed a median puncture-free
survival (primary endpoint) of 46 days compared with 11 days in the control
group (p
the last infusion and the first subsequent necessary puncture or death,
whichever occurred first. The median puncture-free time - a secondary
endpoint which did not include the data from patients who died before the
next ascites puncture was due - was 77 days versus 13 days (p
Patients receiving catumaxomab had an overall survival of 72 days compared
with 68 days in the control group. Improved overall survival of catumaxomab
treated patients with ovarian cancer (110 vs. 81 days; p=0.1543) and gastric
cancer (71 vs. 44 days, p=0.0313) indicate survival benefit.
The most common side effects observed during the trial, such
as fever, nausea and vomiting were all due to catumaxomab's mode of action.
These side effects were predictable, limited, manageable and mostly fully
reversible.
Malignant ascites can be caused by different epithelial
tumors. Abdominal spread of tumor cells leads to an accumulation of fluid in
the abdominal cavity and is associated with a poor prognosis. The most
commonly used treatment of malignant ascites is puncture (paracentesis),
which has to be carried out on average every eleven days and can lead to
complications such as infection and fluid or protein deprivation. The
trifunctional antibody catumaxomab is known to kill tumor cells in the
peritoneal cavity and therefore attacks the primary cause of ascites
formation.
Trifunctional Antibody Catumaxomab
The therapeutic objective of trifunctional antibodies is to
generate a stronger immune reaction against tumor cells. Catumaxomab has two
different antigen binding sites: While one arm of the antibody recognizes and
binds to T cells, the other arm binds EpCAM (epithelial cell adhesion
molecule) that is overexpressed in many types of epithelial cancers. Immune
effector cells with Fc receptors (macrophages, monocytes, dendritic cells and
natural killer cells) can also bind the Fc region of trifunctional
antibodies. This simultaneous binding subsequently results in the
costimulation and activation of T cells and accessory cells, enabling the
generation of a strong immune response against tumor cells. Preclinical and
clinical data also suggest a potential long-lasting effect to prevent cancer
recurrence. Catumaxomab is further developed in various indications (e.g.
gastric and ovarian cancer) in the early stages of disease addressing the
underlying tumor.
Trifunctional Antibodies
Trifunctional antibodies are proteins that activate different
cell types of the immune system simultaneously and redirect them specifically
to tumor cells which are killed. Trifunctional antibodies are therefore very
effective in destroying cancer cells and show a therapeutic effect even at
very low dosages. Apart from catumaxomab two other trifunctional antibodies
targeting other cancer antigens are currently undergoing clinical
development.
Trifunctional antibodies are being developed by TRION Pharma
GmbH.
Fresenius Biotech - a company of the Fresenius health care
group - is focused on the development, marketing and commercialization of
biopharmaceuticals in the fields of oncology and transplantation medicine.
For further information please visit http://www.fresenius-biotech.com.
Fresenius is a health care group with international operations, providing
products and services for dialysis, hospital and outpatient medical care. In
2007, group sales were approx. EUR 11.4 billion. On March 31, 2008 the
Fresenius Group had 116,203 employees worldwide. For further information
please visit www.fresenius.de.
Trion Pharma is a biopharmaceutical company that develops and produces
trifunctional antibodies based on a globally patented technology platform
together with Fresenius Biotech in Munich. For further information please
visit www.trionpharma.de.
This release contains forward-looking statements that are
subject to various risks and uncertainties. Actual results could differ
materially from those described in these forward-looking statements due to
certain factors, including changes in business, economic and competitive
conditions, regulatory reforms, foreign exchange rate fluctuations,
uncertainties in litigation or investigative proceedings, and the
availability of financing. Fresenius does not undertake any responsibility
to update the forward-looking statements in this release.
Joachim Weith, Corporate Communications
Tel.: +49-6172-6082101
Fax: +49-6172-6082294
e-mail: pr-fre@fresenius.de
http://www.fresenius-ag.com
Joachim Weith, Corporate Communications, Tel.: +49-6172-6082101, Fax: +49-6172-6082294, e-mail: pr-fre@fresenius.de
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