# Alizyme is developing renzapride for the treatment of irritable Bowel Syndrome



## Jeffrey Roberts (Apr 15, 1987)

http://www.alizyme.com/products/ATL-1251.htm Alizyme is developing renzapride for the treatment of irritable bowel syndrome (IBS) and is proceeding with a 500 patient Phase IIb clinical trial in constipation-predominant IBS (c-IBS) patients, a 160 patient Phase IIb clinical trial in mixed-symptom IBS (m-IBS) patients and a 48 patient pharmacokinetic/pharmacodynamic study at Mayo Clinic in the USA in c-IBS patients. Renzapride has both 5-HT4 agonist and a 5-HT3 -antagonist activity. These receptors influence intestinal motility and sensitivity. The dual mechanism of action of renzapride gives it a distinctive pharmacology and distinguishes it from its potential competitors. Renzapride was initially discovered at Beecham Research Laboratories. Following a development agreement with SmithKline Beecham, Alizyme gained full ownership of renzapride due to SmithKline Beecham's merger with GlaxoWellcome.In a Phase IIa clinical trial in c-IBS patients, which was completed by Alizyme in 2000, improvements in symptoms occurred with renzapride in both male and female patients.IBS is suffered by approximately one in five adults at some stage in their life and is the most common reason for referral to gastroenterologists. The cause of IBS is not known but the symptoms include abdominal pain and discomfort, abdominal bloating, and constipation and/or diarrhoea. Three main groups of IBS sufferers are recognised: - Constipation-predominant (c-IBS) - Diarrhoea-predominant (d-IBS) - Mixed symptoms (m-IBS) in which patients alternate between episodes of constipation and diarrhoea.


----------



## Jeffrey Roberts (Apr 15, 1987)

http://www.alizyme.com/news/20020925_001.htm 25 SEPTEMBER 2002ALIZYME COMPLETES PATIENT RECRUITMENT IN PHASE IIb CLINICAL TRIAL OF RENZAPRIDE IN IRRITABLE BOWEL SYNDROMECambridge UK, 25 September 2002: Alizyme plc (LSE:AZM) is pleased to announce the completion of patient recruitment in its Phase IIb clinical trial of renzapride in patients with constipation-predominant irritable bowel syndrome (c-IBS).The study, in which over 500 patients have been recruited, is being performed in the primary care setting in the UK. Three doses of renzapride are being compared to placebo in the treatment of c-IBS. Patients currently active in the study will continue until completion of the dosing period of 12 weeks and a 4 week follow-up period. The primary efficacy endpoint for the study is patient assessed adequate relief from abdominal pain and/or discomfort. Secondary efficacy endpoints include the intensity and duration of pain and/or discomfort as well as measurements relating to other gastrointestinal symptoms of c-IBS such as stool frequency and consistency and feeling of bloating. The effect of treatment on quality of life outcomes will also be analysed. Data will be analysed for effects at week 1, week 4 and between weeks 5-12 of treatment, in order to determine the product profile and the acute and chronic effects of renzapride in c-IBS. The study, in which over 500 patients have been recruited, is being performed in the primary care setting in the UK. Three doses of renzapride are being compared to placebo in the treatment of c-IBS. Patients currently active in the study will continue until completion of the dosing period of 12 weeks and a 4 week follow-up period. The primary efficacy endpoint for the study is patient assessed adequate relief from abdominal pain and/or discomfort. Secondary efficacy endpoints include the intensity and duration of pain and/or discomfort as well as measurements relating to other gastrointestinal symptoms of c-IBS such as stool frequency and consistency and feeling of bloating. The effect of treatment on quality of life outcomes will also be analysed. Data will be analysed for effects at week 1, week 4 and between weeks 5-12 of treatment, in order to determine the product profile and the acute and chronic effects of renzapride in c-IBS.Renzapride is also being studied in a Phase IIb clinical trial in mixed-symptom IBS patients, involving a total of up to 160 patients in up to 5 European countries, and in a pharmacokinetic/pharmacodynamic study at Mayo Clinic in the USA, involving up to 48 c-IBS patients.Renzapride has both full 5-HT4 receptor agonist and also 5-HT3 receptor antagonist activity. These 5-HT receptors influence gastrointestinal motility and sensitivity. The dual activity of renzapride gives it a distinct pharmacological profile compared with that of other compounds marketed or being developed for the treatment of IBS.Dr. Richard Palmer (Chief Executive Officer) commented: "The completion of recruitment in this large 500 patient Phase IIb study in c-IBS is a significant milestone in the development of renzapride and is also one of the largest clinical trials conducted by a UK biopharmaceutical company. It marks a major achievement for Alizyme as we continue to build our product development portfolio towards the final stages of clinical development and commercialisation. This large study has been designed to provide robust Phase IIb data and a positive outcome would facilitate entry into Phase III. It would also allow Alizyme to demonstrate the attractiveness of the product to potential marketing partners and exploit the distinct properties of renzapride through a commercially attractive out-licensing deal."For further information, please contact: Dr Richard Palmer, Chief Executive Officer Mr Tim McCarthy, Finance Director ALIZYME plc Tel No: + 44 (0)1223 896000 Lisa Baderoon/ Tim Anderson BUCHANAN COMMUNICATIONS Tel No: + 44 (0)20 7466 5000 --------------------------------------------------------------------------------Editor's Note:Alizyme plc Alizyme is a biopharmaceutical company, based in Cambridge, UK, targeting the treatment and management of gastrointestinal disorders, obesity and diabetes. It has a portfolio of products under development, which in addition to renzapride includes COLAL-PREDï¿½ (Phase III for the maintenance of remission of ulcerative colitis), ATL-962 (Phase IIb for obesity) and ATL-104 (completed Phase I for mucositis). At the appropriate time Alizyme intends to license products to established pharmaceutical companies, who would complete development, gain marketing approval and commercialise the products.Irritable Bowel SyndromeIBS is a common gastrointestinal disorder. Important symptoms include abdominal pain, discomfort and feeling of bloating. In IBS, the normal contractile patterns of the gut are disrupted resulting in irregular or spasmodic bowel movements. Sufferers may experience either a constipation or a diarrhoea predominant form of IBS or, in 'mixed symptom' IBS, alternate between these conditions. It has been estimated that up to 20% of adults in developed countries are affected to some degree by IBS; of these between 20-30% consult a doctor. Current treatments, which are aimed at providing symptomatic relief to IBS sufferers, include laxatives, anti-diarrhoeal and antispasmodic products. These products, however, have limited efficacy for the condition and it is generally accepted that the market is poorly served. In July 2002, Novartis received marketing approval from the Food and Drug Administration in USA, for their product Zelnorm, a 5-HT4 receptor agonist, for the treatment of c-IBS in women. Zelnorm, known internationally as Zelmac, is also approved in more than 30 countries including Australia, Switzerland, Canada and Brazil. It has not yet been approved in Europe RenzaprideAlizyme is currently developing renzapride for the treatment of IBS. Renzapride is a novel benzamide derivative and a potent full 5-HT4 receptor agonist; it is also an antagonist at 5-HT3 receptors. These 5-HT receptors are believed to play a key role in controlling gastrointestinal motility and sensitivity. The distinct, dual pharmacological profile of renzapride differentiates it from other drugs currently in development for the treatment of IBS. Renzapride was discovered by Beecham Research Laboratories and investigated by them initially as a gastrointestinal prokinetic agent for the treatment of gastroesophageal reflux disease. Following a collaborative agreement, Alizyme obtained full ownership of renzapride from SmithKline Beecham prior to its merger with GlaxoWellcome.


----------



## trbell (Nov 1, 2000)

how does this relate to dexlox?tom


----------

