Dublin, Ireland, 7th June 2006
AGI Therapeutics Announces Preliminary Results of Phase II Trials for Gastrointestinal Disorders.
AGI Therapeutics plc (AIM, IEX: AGI, "AGI" or the "Company"), a speciality pharmaceutical company focused on gastrointestinal (GI) drug products, today announces the preliminary results of two Phase II trials of its arverapamil (AGI-003) and espindolol (AGI-001) product candidates.
The results for arverapamil in non-constipation predominant irritable bowel syndrome (IBS) were positive, showing statistically significant superiority versus placebo. The data provides a compelling case for progressing this compound into late stage clinical development.
Arverapamil is targeted at the treatment of patients with IBS, which constitutes a significant unmet medical need and market opportunity. Arverapamil may also have utility in the treatment of other diarrhoea-related conditions.
Results for espindolol in functional dyspepsia were less conclusive and AGI will consider how best to advance the development of the product for this indication once 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 is expected 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 the efficacy of this drug in IBS patients with non-constipation predominant symptoms. These preliminary results will allow us to move forward with the development of arverapamil for IBS and to enter into dialogue with both regulatory agencies and potential commercial partners to progress the product through late stage clinical development. Our overall strategy of identifying a lead product by the end of the year from our broad portfolio for late stage clinical development is very much on track and arverapamil is the third of our six clinical candidates to provide encouraging data this year. We look forward with anticipation to the outcomes of three further Phase II trials in the second half of the year."
Clinical Trial Results Summary - Arverapamil (AGI-003)
The clinical trial was a randomised, double-blind, placebo-controlled, parallel group, forced dose-escalation study, which evaluated the efficacy of arverapamil versus 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 (provided the previous dose was well tolerated), and further dose-escalated to 240mg/day for 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 that were not constipation predominant were randomised in the study. Using an intent-to-treat analysis and the entire 12 weeks of therapy, the arverapamil treated patients showed a significantly higher response rate than placebo based on patient global impression (56.9% vs. 37.5%) and based on relief of abdominal pain/discomfort (56.9% vs. 43.8%). No differences between treatments were seen in use of rescue medications.
Compared with placebo, the arverapamil treated patients also showed significant favourable differences in change from baseline in a) the Bristol Stool Scale at week 8 and week 12, b) bloating and stool frequency at week 4 and c) urgency and composite gastrointestinal symptoms at week 4 and week 12.
Patients also completed the IBS Quality-of-Life (QOL) survey, a validated 34-item condition-specific QOL survey consisting of 8 subscales at the 4, 8 and 12 week visits. Scores can range from 0 to 100 with a higher score indicating better QOL. Significant improvements were recorded in the arverapamil treated patients compared with placebo at week 12 for both the total score (24.9 points vs. 3.55 points) and for all 8 sub-scales and at week 8 for total score and each of the sub-scales with the exception of sexual and relationship sub-scales.
Arverapamil was generally well tolerated and there were no serious adverse events.
Clinical Trial Results Summary - Espindolol (AGI-001)
The clinical trial was a randomised, double-blind, placebo-controlled, parallel group, forced dose-escalation study, which evaluated the efficacy of espindolol versus 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 was dosed in three divided doses as 7.5mg/day for the first 4 weeks, followed by forced escalation, (providing the previous dose was well tolerated), to 15mg/day for the next 4 weeks and further dose-escalated, (providing the previous dose was well tolerated), to 22.5mg/day for the last 4 weeks of therapy.
132 patients (male and female) meeting ROME II criteria (modified) for Functional Dyspepsia were randomised in the study. Using an intent-to-treat analysis and the entire 12 weeks of dose-escalation therapy, the espindolol treated patients failed to show a significantly higher response rate than placebo based on patient global impression (50.8% vs. 41.8%). The espindolol treated patients did almost reach significance in differences versus placebo in change 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 global patient impression for the espindolol treated patients with a baseline severity >3 (i.e. moderate to severe), (42.4% vs. 28.1%). No differences between treatments were seen in use of rescue medications. Compared with placebo, the espindolol treated patients did not show significantly favourable differences in change from baseline in composite or individual symptoms. Espindolol was generally well tolerated and there were no serious adverse events.
Notes to Editors
About Arverapamil (AGI-003)
Arverapamil is an oral dosage form of the R-isomer of verapamil which is being developed by AGI for the treatment of diarrhoea-predominant irritable bowel syndrome ('d-IBS') in both men and women.
IBS is a functional disorder (i.e. an abnormality or disturbance of normal function which cannot be directly attributed to anatomical or biochemical defects) that comprises a cluster of gastrointestinal symptoms which are likely to be life long and can include diarrhoea, constipation, abdominal pain and distension, which vary in intensity. Altered intestinal motility is a major component of IBS and patients are diagnosed and sub-typed according to their predominant symptom of bowel disturbance as either 'd-IBS', constipation-predominant ('c-IBS') or mixed/alternating symptoms of diarrhoea and constipation ('m-IBS').
The prevalence of IBS has been estimated in US population-based studies at between 10 and 20 per cent and surveys conducted in Europe estimate a similar range of IBS prevalence there. It is estimated that there is an approximately equal prevalence of each of the d-IBS, c-IBS and m-IBS sub-types. IBS is reported to be about twice as prevalent in women as in men. Although an estimated 75 per cent or more of current sufferers remain undiagnosed and untreated, IBS remains the most common diagnosis made by gastroenterologists and leads to a substantial reduction in quality of life, accompanied by considerable socio-economic and psychological consequences.
Arverapamil is being targeted to compete in the d-IBS market, which is estimated to account for approximately one third of all IBS patients. The annual market for prescription therapeutic drug products for IBS in the US was estimated at more than US$400 million in 2005 and is predicted to grow rapidly to more than US$1 billion by 2010. These sales are currently largely for products treating the 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 a Phase II clinical trial evaluating the efficacy of the product in the treatment of 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 being developed for the treatment of both functional dyspepsia, a functional disorder of 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 a cluster of chronic or recurrent upper GI symptoms, including early satiety, abdominal distension and fullness and discomfort and pain, not associated with any known structural abnormality. Estimates as to the prevalence of functional dyspepsia vary, with some studies suggesting that it affects up to 25 per cent of the US population annually and accounts for up to 5% of all visits to primary care physicians, while other studies report a prevalence of between 10 and 20 per cent of the population in the US and Europe. The incidence of functional dyspepsia in men and women is similar. No prescription therapeutic drug products have been found to have a high success rate in the treatment of functional dyspepsia and there are as yet no therapeutic drug products approved for its treatment in the US.
The Company has developed a solid oral dosage form of espindolol and a Phase II clinical trial evaluating the efficacy of this product in the treatment of functional dyspepsia has now been completed (see discussion of results above).
A Phase II clinical trial evaluating the efficacy of espindolol in the treatment of irritable bowel syndrome is currently ongoing. This is a randomised, double-blind, placebo-controlled, parallel group, dose escalation trial conducted over multiple sites in Ireland in a total of 67 patients. This study is fully enrolled and the treatment phase is now complete. It is expected that preliminary results of this trial will be available in Q3, 2006.
About AGI
AGI is a speciality pharmaceutical company which is focused on the development and commercialisation of differentiated drug products for gastrointestinal (''GI'') diseases and disorders.
The Company has a portfolio of product candidates derived from the 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, functional dyspepsia, ulcerative colitis and gastro-esophageal reflux disease. 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 six 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. These product candidates are all in clinical development, including five Phase II trials.
AGI intends to complete its ongoing clinical trials and, dependent on the results of these trials, the Company will initiate late stage development of a lead product candidate and will also seek to enter into licensing and development agreements with pharmaceutical companies so as to enhance the global market reach for its products and achieve optimal revenue and value opportunities for the Company
Statements contained within this press release may contain forward-looking comments that involve risks and uncertainties that may cause actual results to vary from those contained in the forward-looking statements. In some cases, you can identify such forward-looking statements by terminology such as 'may', 'will', 'could', 'forecasts', 'expects', 'plans', 'anticipates', 'believes', 'estimates', 'predicts', 'potential', or 'continue'. Predictions and forward-looking references in this press release are subject to the satisfactory progress of research, which is, by nature, unpredictable. Forward projections reflect management's best estimates based on information available at the time of issue.
Contact Information
AGI Therapeutics
David Kelly, Chief Financial Officer
Tel: +353 1 449 3254
Financial Dynamics - UK
Sarah MacLeod
Tel: +44 (0) 20 7831 3113
Financial Dynamics - Ireland
Aisling Garvey
Tel: +353 1 663 3607
For further information please see www.agitherapeutics.com