BioWorld International Correspondent

LONDON - Alizyme plc announced the results of its first U.S. trial of Renzapride in the treatment of constipation-predominant irritable bowel syndrome, showing the drug caused a dose-dependent enhancement of colonic motility, which resulted in improved bowel function scores.

That follows a positive European Phase IIb study reported last October.

Richard Palmer, CEO, told BioWorld International: "This [U.S.] study is in line with what we got in the previous study. In some ways it is better and is as good as we could have hoped for."

The trial was a double-blind, dose-ranging, placebo-controlled pharmacokinetic and pharmacodynamic study involving 48 patients. Patients were treated for between 11 and 14 days and the effects of Renzapride on gastric emptying and colonic transit times were measured, as well as their correlation with blood levels of the drug.

Renzapride was shown to cause substantial, dose-dependent enhancement of colonic motility, which was statistically and clinically significant at the highest dose of 4 mg once daily. Improved bowel function scores were statistically significantly associated with accelerated colonic transit. More patients reported satisfactory relief of symptoms with Renzapride than with placebo.

"This is a small study, but we did see results in line with the European results," Palmer said. "We've shown directly that Renzapride stimulates motility and does it at doses we [used] in our IIb study." Although the trial does not demonstrate long-term efficacy, it represents what could happen in the early stages of treating the disease.

Palmer added that because of the large placebo effect that usually occurs in irritable bowel syndrome (IBS) trials, being able to relate enhanced colonic motility to improved bowel function and symptomatic relief adds to the depth of Alizyme's Phase II data overall.

"You are not going to get a magic bullet, because IBS is a heterogeneous disease," he said. "We now have positive data in 700 patients, which is a very robust Phase II package."

Cambridge-based Alizyme already is progressing plans for Phase III trials on the basis of the European Phase IIb study. Palmer said the U.S. study gives the company more confidence and will be helpful in discussing Phase III trial design with regulators. He is prospecting for commercial partners and said the U.S. trial will be helpful there, too.

"Anybody interested in IBS has always got a nagging thing in the mind about the placebo effect," he said. "Here we have got a nice low placebo effect."

Alizyme also said it filed a patent application on a crystal form of Renzapride with improved pharmaceutical properties. If granted, that would extend the patent life to 2024.

The company is in the process of out-licensing two other Phase III products and in October raised £11.5 million (US$21.3 million) to give it extra financial headroom while it negotiates deals.