Tranzyme Pharma's Motilin Antagonist TZP-201 Shows Potential for Preventing and Treating Chemotherapy-Induced Diarrhea (CID)
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(TM)) 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.
About Tranzyme
Tranzyme Pharma is a biopharmaceutical company which discovers and develops breakthrough small molecule drugs for diseases where there is a high unmet medical need. Tranzyme has developed a pipeline of novel drugs for the treatment of gastrointestinal and metabolic diseases. Tranzyme's proprietary chemistry technology and discovery capabilities provide competitive advantages in developing drugs being sought by pharmaceutical companies. For more information, please visit: www.tranzyme.com.
Contact
Tranzyme Pharma
Vipin K. Garg, Ph.D.
President & CEO
919-313-4764
vgarg@tranzyme.com
or
Eric Nelson, Ph.D.
VP, Business Development
919-313-4759
enelson@tranzyme.com
or
Helmut Thomas, Ph.D., DABT
SVP, Research and Preclinical Development
819-820-6838
hthomas@tranzyme.com
Posted: October 2007
