AGI announces positive results in a Phase II proof of concept study of
AGI-004 in chemotherapy-induced diarrhoea
Dublin, Ireland, 12 March, 2009 - AGI Therapeutics plc ("AGI" or
the"Company") (AIM, IEX: AGI), a speciality pharmaceutical development
company focused on gastrointestinal drug products, today announces
positive results in a Phase II proof of concept study of AGI-004 in the
control of chemotherapy-induced diarrhoea (CID). AGI-004 is a
once-daily controlled release transdermal patch containing the
nicotinic antagonist mecamylamine. The study was conducted in 64
patients across seven sites in Europe and evaluated two doses of
AGI-004 compared to placebo.
The results showed a statistically significant difference in the
primary endpoint of reducing the incidence of patient-recorded
diarrhoea (response defined as less than 4 bowel movements per day). This
was
observed at the higher of two doses of AGI-004 when compared with
placebo. The robust response for the higher dose of AGI-004 was further
supported by a statistically significant difference in the secondary
endpoint of patient recorded severity of diarrhoea, while positive
trends were observed in the other secondary measurement of reduction in
the use of rescue anti-diarrhoeal medications. Non-significant benefit
in the primary endpoint was also observed with the lower dose and, when
diarrhoea was rated by the physician using the National Cancer
Institute (NCI) grading system, both doses demonstrated positive
improvements. Similarly, positive trends were also observed for the
higher dose in the co-primary endpoint of reducing the number of bowel
movements per day.
While some benefit was seen with the lower dose in treating individual
symptoms, the overall results are consistent with a dose response
effect. In addition to the full cycle results described above, an
analysis of acute (first day of chemotherapy) data, confirmed the
robust control of diarrhoea at the higher dose. AGI-004 treatment was
well tolerated across both doses and there were no drug-related serious
adverse events.
Commenting on the results of the study, Dr. John Devane, CEO, said ''We
are pleased with the outcome of this study which we believe supports
the continued development of AGI-004 as a novel anti-diarrhoeal agent.
CID is a common and debilitating side effect which affects many
patients undergoing chemotherapy. Although designed as an exploratory
study, we observed a strong signal of efficacy for AGI-004 across
multiple measurements of diarrhoea, in particular with the higher dose
used in the study. The development of AGI-004 in a convenient
transdermal patch, which can reduce the occurrence of diarrhoea in
chemotherapy patients, offers a significant therapeutic advantage over
current standard of care.''
Contact Information:
AGI Therapeutics plc. Tel: +353 1 449 3254
David Kelly, Chief Financial Officer
FD - UK Tel: +44 (0) 20 7269 7205
Jonathan Birt/John Dineen
FD - Ireland Tel: +353 1 663 3607
Niamh Lyons
Piper Jaffray Limited Tel: +44 (0) 20 3142 8700
Neil Mackison
Will Carnwath
Davy Tel: +353 1 614 8761
John Frain
For further information please see www.agitherapeutics.com.
Notes to Editors:
About AGI-004 and chemotherapy-induced diarrheoa (CID)
AGI-004, a 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 is applied once-daily.
CID is a prevalent and severe side-effect associated with cancer
chemotherapy treatment which 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 (NCI grade 1) to
life-threatening (NCI 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.
Clinical Trial Design and Conduct
The Phase II study was a randomised, double-blind, placebo-controlled,
balanced, parallel-group trial in 64 cancer patients across 7 sites
in Europe. The study evaluated the efficacy of two doses of AGI-004 in
controlling diarrhoea resulting from the administration of
5-Fluourouracil, including capecitabine and/or irinotecan or cisplatin,
compared with placebo, in patients with NCI grade 1 or 2 CID. Patients
were randomly allocated to active treatment or placebo. Treatment was
initiated 24 hours prior to chemotherapy and patients continued to
self-administer AGI-004 or placebo patches once daily during and after
chemotherapy for the duration of the cycle of chemotherapy. Patients
were allowed free access to loperamide or other appropriate medications
on a rescue basis to treat any active episodes of diarrhoea. Treatment
with AGI-004 or placebo was for two consecutive cycles of chemotherapy.
The dose of mecamylamine was escalated over the two cycles from the
lower dose in the first cycle to the higher dose in the second cycle.
About AGI Therapeutics plc
AGI is a speciality pharmaceutical company which is focused on the
development and commercialisation of differentiated drug products for
gastro-intestinal (GI) diseases and disorders. AGI's common shares are
listed on the Alternative Investment Market of the London Stock
Exchange (AIM) and on the Irish Enterprise Exchange of the Irish Stock
Market (IEX) as AGI.
The Company's lead product candidate, RezularTM, is an orally
administered multiple mechanism intestinal regulator, a first-in-class
mechanism for the treatment of diarrhoea-predominant irritable bowel
syndrome (IBS-D). The Company announced in January that a total of 711
patients have been randomised in 123 clinical centres in the United
States, Europe and South America for ARDIS 1. This study is the first
of two ongoing Phase III studies which will be included in a future New
Drug Application (NDA) submission to the Food and Drug Administration
(FDA) for approval of RezularTM in the U.S. Of the total patients
randomised, 63% are in the United States.
The Company has a portfolio of product candidates derived from its
Known Molecular Entity (KME) approach to drug re-profiling and
development. KME is a re-profiling methodology used by the Company to
identify existing therapeutic drugs which typically have been marketed
for a number of years, have established safety profiles and can be
developed for new clinical indications or with improved profiles in
their existing clinical indications. In this way, the Company seeks to
reduce the risk, time and cost of new product development as compared
to the development of new chemical entities.
AGI is developing a range of product candidates to treat a variety of
prevalent GI diseases and disorders, including irritable bowel syndrome
(IBS), dyspeptic symptoms, gastroparesis, ulcerative colitis,
gastro-esophageal reflux disease (GERD) and diarrhoea-related
conditions such as chemotherapy-induced diarrhoea (CID). The Company is
targeting areas of the GI therapeutic drug products market for its
product candidates where there are currently unmet medical needs or
where the effectiveness of existing drug therapies can be further
improved.
The Company has five active clinical stage product candidates which are
either isomers or novel drug delivery formulations of existing approved
drugs and which have established safety and tolerability profiles in
their currently approved clinical indications.
For further information please see www.agitherapeutics.com.
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