2nd Apr 2008 07:01
AGI Therapeutics plc02 April 2008 AGI announces key findings of clinical PK study of arbaclofen (AGI-006) Dublin, Ireland, 2 April 2008 - AGI Therapeutics plc ("AGI" or the "Company")(AIM, IEX: AGI), a speciality pharmaceutical company focused on gastrointestinaldrug products, today announces the key findings of a clinical study to assessthe pharmacokinetic profile of arbaclofen (AGI-006), which is being developedfor the treatment of gastroparesis, a significant gastric condition amongstdiabetics. The pharmacokinetic study was conducted in healthy human volunteers and comparedthe drug exposure profile of arbaclofen, under both fasted and fed conditions,following a single oral administration of a 5mg dose. Arbaclofen contains thepurified R-isomer form of the previously approved drug baclofen (which is anequal mixture of the S- and R-isomers). In addition, this study compared thedrug exposure of arbaclofen (5mg), in terms of both the S- and R-isomer forms ofbaclofen, with a single 10mg oral dose of Lioresal(R) (a marketed form ofracemic baclofen). The key findings were: (1) There were no detectable S-isomer levels following arbaclofen administration and thus no evidence of any interconversion of arbaclofen (R-isomer) to S-isomer in vivo. The S-isomer is believed to partly counteract the activity of the R-isomer, the critical isomer for the beneficial effects of AGI-006 on gut function, and also contribute unwanted side effects through its own actions and effects. (2) Following arbaclofen administration, approximately 80% of the administered dose was recovered in the urine in unchanged form. The high recovery of unchanged R-isomer in the urine following arbaclofen administration indicates there is no significant effect of hepatic metabolism on the kinetics of arbaclofen. (3) There was comparable plasma exposure of R-isomer from 5mg of arbaclofen compared to 10 mg of Lioresal, confirming that the exposure to the R-isomer is no greater following arbaclofen administration when compared with equivalent doses of an approved and marketed form of racemic baclofen. (4) The rate of drug exposure (expressed as time to peak plasma concentration, or "Tmax") and the extent of drug exposure (expressed in terms of both peak plasma concentration, or "Cmax", and area under the plasma concentration curve, or "AUC") following arbaclofen administration were only modestly reduced by food. This demonstrates that acceptable drug exposure can be achieved with AGI-006 in situations where gastric emptying is delayed (in this case food-induced), which is a key feature of the targeted gastroparesis indication. Commenting on the results Dr John Devane said "These findings have importantimplications for the further clinical development of arbaclofen. We can nowproceed in the knowledge that there will be no exposure to the S-isomerfollowing administration of the purified R-isomer form contained in AGI-006. Inaddition, confirmation that the in vivo exposure to the R-isomer followingarbaclofen administration is no greater than is seen with marketed racemicbaclofen will support our 505(b)2 NDA development strategy and the associatedcross-referencing of the pre-clinical and clinical safety history available onracemic baclofen." 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-waycrossover study in nine healthy subjects (4 males, 5 females). The treatmentswere arbaclofen/AGI-006 (5mg) administered under fasting and fed conditions andLioresal(R) (10mg) administered under fasting conditions. Lioresal is anFDA-approved form of racemic baclofen which is used to treat CNS disorders.Blood samples were taken periodically up to 24 hours after each administrationand there was also a cumulative 24 hour collection of urine. Plasma and urineconcentrations of the R- and S-isomers of baclofen were measured using avalidated Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS)method. All treatments in the study were well tolerated. About arbaclofen (AGI-006) Arbaclofen is our product candidate for the treatment of gastroparesis and fordyspeptic conditions such as functional dyspepsia. Gastroparesis is asignificant GI disorder among diabetic patients and affects up to 20% of Type Iand 30% of Type II diabetics. Current drug therapy for gastroparesis is limitedand there is a significant market opportunity for new safe and effectiveproducts. Arbaclofen is an oral dosage form of the predominantpharmacologically active r-isomer of baclofen. About gastroparesis Gastroparesis is a gastric motility disorder where there is delayed gastricemptying and the condition is usually chronic. The primary known cause ofgastroparesis is diabetes and the condition is frequently referred to as 'diabetic gastroparesis'. In diabetic patients (both Types I and II),gastroparesis is caused by prolonged elevated serum glucose levels resulting invagal nerve damage, which in turn leads to impaired gastric motility andemptying. Gastroparesis is estimated to affect up to 30% of Type I and 20% ofType II diabetics. There are an estimated 2.5 million diabetic gastroparesispatients in the US and 1.5 million in Europe, while the incidence is expected torise as the diabetic population continues to increases across the globe. About AGI Therapeutics plc AGI is a speciality pharmaceutical company which is focused on the developmentand commercialisation of differentiated drug products for gastrointestinal (GI)diseases and disorders. AGI's common shares are listed on the AlternativeInvestment Market of the London Stock Exchange (AIM) and on the Irish EnterpriseExchange of the Irish Stock Market (IEX) as AGI. The Company has a portfolio of product candidates derived from its KnownMolecular Entity (KME) approach to drug re-profiling and development. KME is are-profiling methodology used by the Company to identify existing therapeuticdrugs which typically have been marketed for a number of years, have establishedsafety profiles and can be developed for new clinical indications or withimproved profiles in their existing clinical indications. In this way, theCompany seeks to reduce the risk, time and cost of new product development ascompared to the development of new chemical entities. AGI is developing a range of product candidates to treat a variety of prevalentGI diseases and disorders, including irritable bowel syndrome (IBS), dyspepsia,gastroparesis, ulcerative colitis, gastro-esophageal reflux disease (GERD) anddiarrhoea-related conditions such as chemotherapy-induced diarrhoea (CID). TheCompany is targeting areas of the GI therapeutic drug products market for itsproduct candidates where there are currently unmet medical needs or where theeffectiveness of existing drug therapies can be further improved. The Company has five active clinical stage product candidates which are eitherisomers or new drug delivery formulations of existing approved drugs, and whichhave established safety and tolerability profiles in their currently approvedclinical indications. For further information please see www.agitherapeutics.com Statements contained within this press release may contain forward-lookingcomments which involve risks and uncertainties that may cause actual results tovary from those contained in the forward-looking statements. In some cases, youcan identify such forward-looking statements by terminology such as 'may', 'will', 'could', 'forecasts', 'expects', 'plans', 'anticipates', 'believes', 'estimates', 'predicts', 'potential', or 'continue'. Predictions andforward-looking references in this press release are subject to the satisfactoryprogress of research which is, by nature, unpredictable. Forward projectionsreflect management's best estimates based on information available at the timeof issue. This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
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