AGI Therapeutics plc, a speciality pharmaceutical company focused on gastrointestinal drug products, announces that the first patient has been dosed in its phase II study of AGI-004 in the treatment of chemotherapy-induced diarrhoea (CID).
The current standard of care for CID patients usually involves multiple oral daily doses of an opioid agent such as loperamide. However, many patients who receive loperamide continue to experience significant and debilitating diarrhoea which may require reduction, delay or even withdrawal of chemotherapy. AGI-004 is a controlled release transdermal patch containing the nicotinic antagonist mecamylamine. The patch involves a new anti-diarrhoeal mechanism via selective blockade of enteric nicotinic acetylcholine receptors (nAChR) and offers a significant advantage to current CID therapy via its convenient, once-daily transdermal form.
AGI previously reported data demonstrating a statistically significant improvement in stool consistency in patients with functional diarrhoea. The Phase II study is a randomised, double-blind, placebo-controlled evaluation of AGI-004 in cancer patients experiencing National Cancer Institute (NCI) grade 1 or 2 CID.
Dr. John Devane, CEO of AGI, commented; "We believe AGI-004 has the potential to address a significant need for a more effective anti-diarrhoeal therapy for patients undergoing chemotherapy and are very encouraged by the initiation of dosing in this study population. We are pleased to see continued progress of our product pipeline and, in addition to the pivotal phase III programme for Rezular in IBS-D, we look forward to further developments in our phase II programmes during the course of 2008.
AGI-004 is a controlled release transdermal patch containing mecamylamine designed for once-daily administration. AGI-004 is the subject of a number of pending patent applications, the first of which was recently granted in the European patent office (EP 1603544).
Previously, AGI reported the results of a phase II clinical study in patients with functional diarrhoea. This study was designed to investigate the anti-diarrhoeal profile of AGI-004 and identify clinical signals which would inform further clinical development. Data from this pilot study demonstrated that AGI-004 has a beneficial effect on certain diarrhoea-related symptoms, particularly stool consistency. Based on these clinical data, the mechanism of action of AGI-004 and the pathophysiology of certain non-functional diarrhoea conditions, the Company determined that AGI-004 may be effective in treating diarrhoea-related symptoms in conditions such as chemotherapy-induced diarrhoea (CID).
CID is a prevalent and severe toxicity associated with cancer chemotherapy treatment and occurs in up to 50% of patients receiving chemotherapy and can affect up to 80% of patients receiving certain chemotherapy regimens. CID may range from troublesome (grade 1) to life-threatening (grade 4). CID can negatively impact a patient's health to the point that they are unable to tolerate their prescribed chemotherapy, commonly leading to delay or reduction in treatment which may diminish the effect of treatment. Loperamide is the current drug of choice for the management of mild to moderate CID, but is limited in terms of its effectiveness and dosing flexibility, and there are currently few effective alternative therapies available.
AGI-004, a low-dose controlled release form of mecamylamine, is a potent, non-competitive specific antagonist at nicotinic Acetylcholine receptors (nAChR). More specifically, AGI-004 has been shown to be selectively active on certain nAChR sub-types which are the predominant form found on enteric neurons, where nAChR is known to regulate a range of gut functions, including modulation of secretory and motility effects. AGI-004 is formulated in a proprietary controlled release transdermal patch which can be administered one-daily.
The current phase II study is a randomised, prospective, multi-centre, double-blind, placebo-controlled, balanced, parallel-group trial in cancer patients who are experiencing grade 1 or 2 CID. Patients will be randomly allocated to active treatment or placebo. Treatment will be initiated 24 hours prior to chemotherapy. Patients will continue to self-administer AGI-004 or placebo patches once daily during and after chemotherapy for the duration of the cycle. Patients will be allowed free access to loperamide or other appropriate medications on a rescue basis for the duration of any active episodes of diarrhoea. Treatment with AGI-004 or placebo will be for two consecutive cycles of chemotherapy. The dose of mecamylamine will be escalated over the two cycles.
AGI is a speciality pharmaceutical company which is focused on the development and commercialisation of differentiated drug products for gastrointestinal ('GI') diseases and disorders.