7th Jun 2006 07:02
AGI Therapeutics plc07 June 2006 AGI Therapeutics Announces Preliminary Results of Phase II Trials for Gastrointestinal Disorders Dublin, Ireland, 7 June 2006 - AGI Therapeutics plc (AIM, IEX: AGI, "AGI" orthe "Company"), a speciality pharmaceutical company focused on gastrointestinal(GI) drug products, today announces the preliminary results of two Phase IItrials of its arverapamil (AGI-003) and espindolol (AGI-001) product candidates. The results for arverapamil in non-constipation predominant irritable bowelsyndrome (IBS) were positive, showing statistically significant superiorityversus placebo. The data provides a compelling case for progressing thiscompound into late stage clinical development. Arverapamil is targeted at the treatment of patients with IBS, which constitutesa significant unmet medical need and market opportunity. Arverapamil may alsohave utility in the treatment of other diarrhoea-related conditions. Results for espindolol in functional dyspepsia were less conclusive and AGI willconsider how best to advance the development of the product for this indicationonce all of the data from the current trial have been fully analysed.Espindolol is the subject of a separate, ongoing Phase II trial in IBS which isexpected to be reported during the third quarter this year. Commenting on the results, Dr. John Devane, CEO of AGI, said: "We are delighted by the outcome of the arverapamil trial, which supports theefficacy of this drug in IBS patients with non-constipation predominantsymptoms. These preliminary results will allow us to move forward with thedevelopment of arverapamil for IBS and to enter into dialogue with bothregulatory agencies and potential commercial partners to progress the productthrough late stage clinical development. Our overall strategy of identifying alead product by the end of the year from our broad portfolio for late stageclinical development is very much on track and arverapamil is the third of oursix clinical candidates to provide encouraging data this year. We look forwardwith anticipation to the outcomes of three further Phase II trials in the secondhalf of the year." Clinical Trial Results Summary - Arverapamil (AGI-003) The clinical trial was a randomised, double-blind, placebo-controlled, parallelgroup, forced dose-escalation study, which evaluated the efficacy of arverapamilversus placebo over a 12-week period following an 8-14 day run-in period.Arverapamil was dosed in three divided doses as 60mg/day for the first 4 weeks,followed by forced dose-escalation to 120mg/day for the next 4 weeks (providedthe previous dose was well tolerated), and further dose-escalated to 240mg/dayfor the last 4 weeks of therapy (provided the previous dose was well tolerated). 129 patients (male and female) meeting ROME II criteria (modified) for IBS thatwere not constipation predominant were randomised in the study. Using anintent-to-treat analysis and the entire 12 weeks of therapy, the arverapamiltreated patients showed a significantly higher response rate than placebo basedon patient global impression (56.9% vs. 37.5%) and based on relief of abdominalpain/discomfort (56.9% vs. 43.8%). No differences between treatments were seenin use of rescue medications. Compared with placebo, the arverapamil treated patients also showed significantfavourable differences in change from baseline in a) the Bristol Stool Scale atweek 8 and week 12, b) bloating and stool frequency at week 4 and c) urgency andcomposite gastrointestinal symptoms at week 4 and week 12. Patients also completed the IBS Quality-of-Life (QOL) survey, a validated34-item condition-specific QOL survey consisting of 8 subscales at the 4, 8 and12 week visits. Scores can range from 0 to 100 with a higher score indicatingbetter QOL. Significant improvements were recorded in the arverapamil treatedpatients compared with placebo at week 12 for both the total score (24.9 pointsvs. 3.55 points) and for all 8 sub-scales and at week 8 for total score and eachof the sub-scales with the exception of sexual and relationship sub-scales. Arverapamil was generally well tolerated and there were no serious adverseevents. Clinical Trial Results Summary - Espindolol (AGI-001) The clinical trial was a randomised, double-blind, placebo-controlled, parallelgroup, forced dose-escalation study, which evaluated the efficacy of espindololversus placebo over a 12-week period following an 8-14 day run-in period.Thereafter there was a 1 week down-titration to being drug free. Espindolol wasdosed in three divided doses as 7.5mg/day for the first 4 weeks, followed byforced escalation, (providing the previous dose was well tolerated), to 15mg/dayfor the next 4 weeks and further dose-escalated, (providing the previous dosewas well tolerated), to 22.5mg/day for the last 4 weeks of therapy. 132 patients (male and female) meeting ROME II criteria (modified) forFunctional Dyspepsia were randomised in the study. Using an intent-to-treatanalysis and the entire 12 weeks of dose-escalation therapy, the espindololtreated patients failed to show a significantly higher response rate thanplacebo based on patient global impression (50.8% vs. 41.8%). The espindololtreated patients did almost reach significance in differences versus placebo inchange from baseline in global severity of illness at week 4 (-0.89 vs. -0.57).A sub-analysis showed a significantly higher response rate based on globalpatient impression for the espindolol treated patients with a baseline severity>3 (i.e. moderate to severe), (42.4% vs. 28.1%). No differences betweentreatments were seen in use of rescue medications. Compared with placebo, theespindolol treated patients did not show significantly favourable differences inchange from baseline in composite or individual symptoms. Espindolol wasgenerally well tolerated and there were no serious adverse events. Contact Information: AGI David G. Kelly, Chief Financial Officer Tel: +353 1 449 3254 Financial Dynamics - UK Tel: +44 (0) 20 7831 3113 Sarah MacLeod Financial Dynamics - Ireland Tel: +353 1 663 3607 Aisling Garvey For further information please see www.agitherapeutics.com NOTES TO EDITORS About Arverapamil (AGI-003) Arverapamil is an oral dosage form of the R-isomer of verapamil which is beingdeveloped by AGI for the treatment of diarrhoea-predominant irritable bowelsyndrome ('d-IBS') in both men and women. IBS is a functional disorder (i.e. an abnormality or disturbance of normalfunction which cannot be directly attributed to anatomical or biochemicaldefects) that comprises a cluster of gastrointestinal symptoms which are likelyto be life long and can include diarrhoea, constipation, abdominal pain anddistension, which vary in intensity. Altered intestinal motility is a majorcomponent of IBS and patients are diagnosed and sub-typed according to theirpredominant symptom of bowel disturbance as either 'd-IBS',constipation-predominant ('c-IBS') or mixed/alternating symptoms of diarrhoeaand constipation ('m-IBS'). The prevalence of IBS has been estimated in US population-based studies atbetween 10 and 20 per cent and surveys conducted in Europe estimate a similarrange of IBS prevalence there. It is estimated that there is an approximatelyequal prevalence of each of the d-IBS, c-IBS and m-IBS sub-types. IBS isreported to be about twice as prevalent in women as in men. Although anestimated 75 per cent or more of current sufferers remain undiagnosed anduntreated, IBS remains the most common diagnosis made by gastroenterologists andleads to a substantial reduction in quality of life, accompanied by considerablesocio-economic and psychological consequences. Arverapamil is being targeted to compete in the d-IBS market, which is estimatedto account for approximately one third of all IBS patients. The annual marketfor prescription therapeutic drug products for IBS in the US was estimated atmore than US$400 million in 2005 and is predicted to grow rapidly to more thanUS$1 billion by 2010. These sales are currently largely for products treatingthe c-IBS component, and whose use is currently restricted to women only. A solid oral dosage form of arverapamil has been developed by the Company and aPhase II clinical trial evaluating the efficacy of the product in the treatmentof non-constipation predominant irritable bowel syndrome has now been completed(see discussion of the results above). About Espindolol (AGI-001) Espindolol is an oral dosage form of the S-isomer of pindolol which is beingdeveloped for the treatment of both functional dyspepsia, a functional disorderof the upper GI tract, and irritable bowel syndrome (IBS) in both men and women. Functional dyspepsia, also referred to as non-ulcer dyspepsia or NUD, is acluster of chronic or recurrent upper GI symptoms, including early satiety,abdominal distension and fullness and discomfort and pain, not associated withany known structural abnormality. Estimates as to the prevalence of functionaldyspepsia vary, with some studies suggesting that it affects up to 25 per centof the US population annually and accounts for up to 5% of all visits to primarycare physicians, while other studies report a prevalence of between 10 and 20per cent of the population in the US and Europe. The incidence of functionaldyspepsia in men and women is similar. No prescription therapeutic drug productshave been found to have a high success rate in the treatment of functionaldyspepsia and there are as yet no therapeutic drug products approved for itstreatment in the US. The Company has developed a solid oral dosage form of espindolol and a Phase IIclinical trial evaluating the efficacy of this product in the treatment offunctional dyspepsia has now been completed (see discussion of results above). A Phase II clinical trial evaluating the efficacy of espindolol in the treatmentof irritable bowel syndrome is currently ongoing. This is a randomised,double-blind, placebo-controlled, parallel group, dose escalation trialconducted over multiple sites in Ireland in a total of 67 patients. This studyis fully enrolled and the treatment phase is now complete. It is expected thatpreliminary results of this trial will be available in Q3, 2006. About AGI AGI is a speciality pharmaceutical company which is focused on the developmentand commercialisation of differentiated drug products for gastrointestinal (''GI'') diseases and disorders. 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 is developing a range of product candidates to treat a variety of prevalentGI diseases and disorders, including irritable bowel syndrome, functionaldyspepsia, ulcerative colitis and gastro-esophageal reflux disease. The Companyis targeting areas of the GI therapeutic drug products market for its productcandidates where there are currently unmet medical needs or where theeffectiveness of existing drug therapies can be further improved. The Company has six clinical stage product candidates which are either isomersor new drug delivery formulations of existing approved drugs, and which haveestablished safety and tolerability profiles in their currently approvedclinical indications. These product candidates are all in clinical development,including five Phase II trials. AGI intends to complete its ongoing clinical trials and, dependent on theresults of these trials, the Company will initiate late stage development of alead product candidate and will also seek to enter into licensing anddevelopment agreements with pharmaceutical companies so as to enhance the globalmarket reach for its products and achieve optimal revenue and valueopportunities for the Company Statements contained within this press release may contain forward-lookingcomments that 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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