Clinical study supports the pharmacokinetic and safety profile of RezularTM
Dublin, Ireland, 21 February 2008 - AGI Therapeutics plc ("AGI" or the
"Company") (AIM, IEX: AGI), a speciality pharmaceutical company focused on
gastrointestinal drug products, today announces the key findings of a clinical
study to assess the pharmacokinetic profile of RezularTM (AGI-003), which is in
Phase III clinical trials for the treatment of diarrhoea-predominant irritable
bowel syndrome (IBS-D).
The pharmacokinetic study was conducted in healthy human volunteers and compared
the drug exposure profile (in terms of both peak plasma concentration, or "Cmax
", and area under the plasma concentration curve, or "AUC") after administration
of 80mg of Rezular, under fed and fasting conditions, to 160mg of a marketed
form of racemic verapamil. Rezular contains arverapamil, the purified R-isomer
form of verapamil, whereas racemic verapamil contains equal amounts of the R-
and the S-isomer.
The key findings of the study were:
(1) There were no detectable levels of the S-isomer following Rezular
administration under fasting conditions and thus no evidence of any
inter-conversion of Rezular to the S-isomer in vivo. Administration of
Rezular under fed conditions resulted in some increase in AUC of the
R-isomer compared to fasting conditions, while the S-isomer was only
detected in the plasma at trace levels matching the trace amounts known
to be present in the purified form of Rezular. These data indicate
that the gastrointestinally active R-isomer, arverapamil, contained in
Rezular can be administered to humans without exposing them to
clinically relevant levels of the S-isomer, the form of verapamil which
is most potent on cardiac and vascular tissue; and
(2) Under both fed and fasting conditions, both the Cmax and AUC of the
R-isomer after Rezular administration were less than those seen after
administration of racemic verapamil. This indicates that patients
taking clinically relevant doses of Rezular will be exposed to lower
systemic levels of the R-isomer compared to currently approved forms of
racemic verapamil, and further supports the NDA 505(b)2-based
development approach agreed with the US Food and Drug Administration
(FDA) for Rezular.
Commenting on the results, Dr John Devane, CEO of AGI, said:
"Verapamil has been on the market in the US for over 20 years, however the
presence of the S-isomer does not allow the use of racemic verapamil to safely
treat gastrointestinal conditions such as irritable bowel syndrome. We believe
that Rezular has important safety benefits in the treatment of
gastrointestinal-related disorders. The findings from this pharmacokinetic
study further support the safety profile of Rezular and the development strategy
being pursued by the Company."
Contact Information:
AGI Therapeutics plc. Tel: +353 1 449 3254
David Kelly, Chief Financial Officer
Financial Dynamics - UK Tel: +44 (0) 20 7269 7182
Deborah Scott/Lara Mott
Financial Dynamics - Ireland Tel: +353 1 663 3607
Aisling Garvey
Piper Jaffray Limited Tel: +44 (0) 20 3142 8700
Neil Mackison
Will Carnwath
Davy Tel: +353 1 614 8761
John Frain
Notes to Editors:
About the study
The pharmacokinetic study was a single-dose, open-label, randomized, three-way
crossover study in 16 healthy subjects (8 males, 8 females). The treatments
were RezularTM (80mg) administered under fasting and fed conditions and Calan(R)
(160mg) administered under fasting conditions. Calan is an FDA-approved form of
racemic verapamil which is used to treat cardiovascular disorders. Blood samples
were taken periodically up to 48 hours after each administration. Plasma
concentrations of the R- and S-isomers of verapamil were measured using a
validated Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS)
method. All treatments in the study were well tolerated.
About RezularTM
Rezular is an orally administered triple-action intestinal regulator, a
first-in-class mechanism for the treatment of IBS-D. Rezular contains
arverapamil, the pure R-isomer form of the racemic drug verapamil. Unlike the
currently available commercial forms of verapamil (a racemic mixture of two
isomers, R and S), Rezular shows a dominant activity in treating the symptoms of
IBS-D without the traditional cardiovascular actions exerted by the S-isomer
component of the racemic drug. The efficacy and safety of Rezular in IBS
patients has already been established in a Phase II trial, the preliminary
results of which were reported by the Company in 2006 and presented at the 2007
Scientific Meeting of the American College of Gastroenterology. Rezular is
currently in Phase III clinical trials (ARDIS) for the treatment of IBS-D.
About ARDIS
ARDIS represents AGI's Phase III programme for Rezular in the treatment of IBS-D
and consists of three pivotal studies.
ARDIS-1 is a randomised, double-blind, placebo-controlled, parallel group, Phase
III study in IBS-D patients (both men and women). There are four treatment arms
(placebo and three dose levels of Rezular) and patients will be treated for 12
weeks of double-blind therapy. At the end of double-blind therapy in ARDIS-1,
patients will become eligible to enrol into ARDIS-3. It is planned to randomise
1,200 patients into ARDIS-1.
ARDIS-2 is a confirmatory Phase III efficacy/safety study to be conducted in
IBS-D patients upon completion of ARDIS-1.
ARDIS-3 is an open-label safety study designed to capture 1 year extended safety
in approximately 100 patients on continuous Rezular therapy.
About IBS-D
Irritable bowel syndrome (IBS) is a functional disorder that comprises a cluster
of gastrointestinal symptoms which are likely to be life long and which affect
between 10% and 20% of the population in developed markets. IBS remains the
most common diagnosis made by gastroenterologists and can lead to a substantial
reduction in patients' quality of life, accompanied by considerable
socio-economic and psychological consequences. Altered intestinal motility is a
major component of IBS and patients are diagnosed and sub-typed according to
their predominant symptom of bowel disturbance. Diarrhoea-predominant irritable
bowel syndrome (IBS-D) is estimated to occur in one-third of all IBS patients.
IBS-D represents a significant unmet medical need as there are currently few
safe and effective therapeutic options available to these patients.
About AGI Therapeutics plc
AGI is a speciality pharmaceutical company which is focused on the development
and commercialisation of differentiated drug products for gastrointestinal (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 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), dyspepsia,
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 new 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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AGI Therapeutics plc announces Research Update
| Source: AGI Therapeutics plc
Dublin, Ireland--(Marketwire - February 21, 2008) -