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Tranzyme Pharma’s Motilin Antagonist TZP-201 Shows Potential for Preventing and
Treating Chemotherapy-Induced Diarrhea (CID)
RESEARCH TRIANGLE PARK, N.C.
and SHERBROOKE, Québec (October 24, 2007) - Tranzyme
Pharma, a leading biopharmaceutical company developing small
molecule drugs for the treatment of gastrointestinal and
metabolic diseases, announced today that its Senior Vice
President of Research and Preclinical Development, Dr. Helmut
Thomas, will present results of a preclinical proof-of-concept
study with its first-in-class motilin receptor antagonist
TZP-201 at the 2007 AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics to be held in San
Francisco, CA, on October 25, 2007.
Tranzyme is developing TZP-201, a highly potent and selective
motilin antagonist, for the treatment of gastrointestinal
hypermotility disorders of various origins including
chemotherapy-induced diarrhea (CID). TZP-201 is the latest
clinical candidate to emanate from Tranzyme Pharma’s
breakthrough small molecule macrocyclic (MATCH™) drug discovery
technology.
In the presentation entitled “The Motilin Receptor Antagonist
TZP-201 is Highly Effective in the Control of Irinotecan Induced
Diarrhea in Beagle Dogs”, Dr. Thomas will present data
indicating that TZP-201 can dose-dependently prevent or
substantially mitigate otherwise lethal irinotecan-induced
diarrhea under conditions mimicking the clinical situation. In
the study, TZP-201 was shown to achieve its desired therapeutic
results by reducing symptom severity and restoring normal
motility more effectively, more rapidly, and for a longer
duration than the most common current drug treatment options,
loperamide and octreotide. The study also provided excellent
pharmacokinetic and safety data to support continued development
of the compound.
“I am particularly excited that TZP-201 is not only highly
effective in the control of established CID, but even more so in
the prevention of recurrence after repeated cycles of
chemotherapy” commented Dr. Thomas. “It may well be that we are
on a pathway to prevent CID in a manner equivalent to the
ability of modern cancer support therapeutics to prevent
chemotherapy-induced nausea and vomiting. This property of the
drug opens a new door to cytotoxic chemotherapy by likely
enabling an increase of dose and duration of treatment with
improved chances of completely eliminating malignancies at an
earlier stage and preventing the appearance of resistant tumor
cells.”
About Chemotherapy Induced Diarrhea (CID)
Diarrhea is a common and serious side effect experienced by
cancer patients as a result of the detrimental effects of
cytotoxic chemotherapy on the gastrointestinal tract. The
incidence of CID varies depending on the chemotherapeutic
agent(s) used and drug dosing. In general, it is estimated that
10% of patients with advanced cancer experience acute or
persistent diarrhea that may range from troublesome (grade 1) to
lethal (grade 5) based on the National Cancer Institute-Common
Toxicity Criteria (NCI-CTC). Certain chemotherapy regimens,
particularly those including fluoropyrimidines (i.e., 5-FU),
epothiolones and irinotecan, can result in diarrhea in 50% to
80% of patients, and more than 30% of patients may experience
grade 3 to 5 diarrhea.
CID markedly impairs patient quality of life, creating increased
anxiety, depression, discomfort, and even travel limitations. At
its extreme, diarrhea can also lead to life threatening
complications, including critical electrolyte imbalance,
malnutrition, dehydration and hemodynamic collapse. Importantly,
CID can also negatively impact a patient’s treatment outcome by
necessitating dose reductions and interruptions in treatment,
which consequently can result in cancer disease progression or
shorter survival.
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