1st Feb 2007 07:00
AGI Therapeutics plc01 February 2007 AGI Therapeutics plc Preliminary clinical data for mecamylamine (AGI-004) and arbaclofen (AGI-006) Dublin, Ireland, 1st February, 2007 - AGI Therapeutics plc ("AGI" or the"Company") (AIM, IEX: AGI), a speciality pharmaceutical company focused ongastrointestinal drug products, today announces preliminary results of Phase IIstudies for mecamylamine (AGI-004, for functional diarrhoea) and arbaclofen(AGI-006 for functional dyspepsia). The results of these studies follow thereporting last year of positive results for other AGI products in development. Both were pilot studies designed to identify clinical signals that wouldindicate how to proceed to further clinical development. Both studies showedstatistical significance in a number of endpoints, which point to theirpotential clinical utility in certain related GI indications, although theprimary endpoints in the specific patient populations were not met. Bothproducts will now be progressed into further clinical trials for related,alternative indications. Evidence from the mecamylamine study suggests that mecamylamine has a beneficialeffect on certain diarrhoea-related symptoms, particularly stool consistency.Based on the signals identified in the current study, the mechanism of action ofmecamylamine and the pathophysiology of certain non-functional diarrhoeaconditions, this study suggested that mecamylamine may be effective in treatingdiarrhoea-related symptoms in conditions such as chemotherapy-related diarrhoea.AGI intends to initiate further Phase II clinical evaluation of mecamylamine inthe second half of 2007. The arbaclofen clinical study showed strong evidence that arbaclofen has abeneficial effect on a number of clinically important gastrointestinal symptomstypical of dyspepsia. The symptoms affected appear consistent with theprokinetic activity of arbaclofen and may have particular relevance in thetreatment of dyspeptic symptoms associated with gastroparesis in diabetics orwith certain sub-sets of the functional dyspepsia population, both of which areimportant commercial markets. AGI expects to commence a larger and more rigorousPhase II trial in the second half of this year. Dr. John Devane, CEO of AGI said: "We are pleased with the positive signals pointing to potential therapeuticbenefit in both these compounds and believe further clinical development isjustified. The result of these two trials completes the current programme ofclinical work on six products which have been evaluated in a variety of GIdiseases. The results of the clinical trials on the other four products werereported in 2006. We are highly encouraged with the success we have had so faracross our portfolio and can now set out a strategy to progress these products.We look forward to updating our shareholders of these plans in the near future." Contact Information: AGI Therapeutics plc.Tel: +353 1 449 3254David Kelly, Chief Financial Officer Financial Dynamics - UKTel: +44 (0) 20 7831 3113Anna Keeble Financial Dynamics - IrelandTel: +353 1 663 3607Aisling Garvey For further information please see www.agitherapeutics.com Notes to Editors Mecamylamine (AGI-004) Preliminary results for mecamylamine in functional diarrhoea: The clinical trial was a randomised, double-blind, placebo-controlled,parallel-group, forced dose-escalation study which evaluated the efficacy ofmecamylamine versus placebo over a 12-week period following an 8-14 day run-inperiod. Mecamylamine was dosed once daily as 2mg/day for the first 4 weeks,followed by forced titration, providing the previous dose was well tolerated, to4mg/day for the next 4 weeks and further dose-escalated, providing the previousdose was well tolerated, to 6mg/day for the last 4 weeks of therapy. 82 patients (male and female) meeting ROME II criteria (modified) for functionaldiarrhoea were randomised in the study. Using an intent-to-treat analysis andthe entire 12 weeks of dose-escalation therapy, the mecamylamine treatedpatients failed to show a statistically significant difference from placebo inthe primary and secondary endpoints with the exception of an improvement instool consistency at week 4 (the 2mg/day treatment period) based on positiveresponses on at least 50% of the available daily reports. However, significant improvements in stool consistency with mecamylaminetreatment compared to placebo were noted in a smaller modified per-protocolpopulation (n=35) for the entire dose-escalation as well as for each dosetreatment phase. The overall incidence of adverse events (AE's) was similar for both mecamylamineand placebo-treated patients. Three patients (two on mecamylamine and one onplacebo) experienced a total of 4 serious AE's all of which were assessed asunrelated to study medication. There were more AE related withdrawals in themecamylamine group (11) compared with placebo (6). Arbaclofen (AGI-006) Preliminary results for arbaclofen in functional dyspepsia: The clinical trial was a randomised, double-blind, placebo-controlled,parallel-group, forced dose-escalation study, which was designed to evaluateinitial signals of efficacy of arbaclofen versus placebo over a 6-week periodfollowing an 8-14 day run-in period. Thereafter there was a 1 weekdown-titration to being drug free. Arbaclofen was dosed in three divided dosesas 7.5mg/day for the first 2 weeks, followed by forced titration, providing theprevious dose was well tolerated, to 15mg/day for the next 2 weeks and furtherdose-escalated, providing the previous dose was well tolerated, to 30.0mg/dayfor the last 2 weeks of therapy. 64 patients (male and female) meeting ROME II criteria (modified) for functionaldyspepsia (FD) were randomised in the study. Using an intent-to-treat analysisand the entire 6 weeks of dose-escalation therapy, the arbaclofen treatedpatients failed to show a statistically significant difference from placebo inthe primary endpoint based on patient global impression. However, the effect of arbaclofen on a number of secondary endpoints wasencouraging. More specifically, positive trends in the change from baseline inupper abdominal fullness and early satiety were observed at all study visits(all doses) and in upper abdominal pain/discomfort at the last visit (thehighest dose) compared to placebo, while significant improvements weredemonstrated for severity of illness, gastrointestinal symptoms, bloating, andnausea at the highest dose visit with trends to improvement in the overall (allvisits) treatment response. In addition, significant differences in rescueantacid use were observed at all visits, with the arbaclofen-treated groupshowing overall lower antacid use. Further differences showing improved qualityof life symptom scores for arbaclofen-treated patients were observed at theinitial treatment visit for emotional score, the mental health score and theoverall mental component summary score with positive trends in the socialfunctioning score and the physical score. Although primary endpoints forfunctional dyspepsia were not met in this pilot study, the therapeutic benefitwas apparent based on the positive effect on numerous secondary endpoints. . The overall incidence of adverse events (AEs) were similar between thearbaclofen and placebo treated patients, however, the incidence of CNS adverseevents (headache, dizziness and somnolence) were greater in thearbaclofen-treated group than the placebo group. There were no serious AEs. Therate of premature withdrawals (drop-outs) was higher in the placebo group (9)than in the arbaclofen-treated group (6). 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 IrishEnterprise Exchange of the Irish Stock Market ("IEX") as "AGI". The Company has a portfolio of product candidates derived from the KnownMolecular Entity (''KME'') approach to drug re-profiling and development. KME isa re-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 has developed a range of product candidates to treat a variety of prevalentGI diseases and disorders, including irritable bowel syndrome (IBS), functionaldyspepsia, ulcerative colitis and gastro-esophageal reflux disease (GERD). 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 clinical stage product candidates which are either isomers ornew drug delivery formulations of existing approved drugs, and which haveestablished safety and tolerability profiles in their currently approvedclinical indications. AGI intends to complete its ongoing clinical trials and, dependent on theresults of these trials, the Company will initiate late stage clinicaldevelopment of lead product candidates and will also seek to enter intolicensing and development agreements with pharmaceutical companies so as toenhance the global market reach for its products and achieve optimal revenue andvalue opportunities for the Company. This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
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