BioWorld International Correspondent
LONDON - Alizyme plc announced positive results in a Phase IIb trial of renzapride in irritable bowel syndrome, enabling the company to initiate discussions with potential licensees and begin the design of the Phase III trials.
The study in 510 patients with constipation-predominant IBS (c-IBS) showed an efficacy profile across a range of symptoms that was equivalent to Novartis AG's Zelmac/Zelnorm, the only drug approved for these patients.
CEO Richard Palmer told BioWorld International, "We are pleased because the thing about Phase II is to get robust enough data to decide whether to go forward into Phase III, and how to do this. This trial was similar in size to [Zelmac trials carried out by] Novartis."
The trial was a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study. In an indication where there generally is a high placebo effect, treatment with renzapride increased the responder rate for adequate relief of abdominal pain and discomfort by up to 9 percent over placebo. Renzapride also increased frequency of bowel movements and improved stool consistency, effects that were dose related. The treatment was safe and well tolerated at all doses.
Alizyme, of Cambridge, also is conducting a 170-patient trial of renzapride in patients with alternating, or mixed-symptom, IBM (m-IBS), which is expected to report preliminary results in October. In addition, a pharmacokinetic trial is aiming to establish the relationship between levels of the drug absorbed and gastrointestinal motility in c-IBS patients.
"The data is good enough in its present form to interest someone in it," Palmer said. "But we will wait for the Phase II results in mixed-symptom patients in October before we finalize the Phase III design. In the meantime there are other analyses to do on this data, to see if we can fine-tune which patients go into Phase III."
Renzapride, a novel benzamide derivative, is a 5-HT4 receptor agonist, and an antagonist for 5-HT3 receptors, both of which are believed to play a key role in controlling gastrointestinal motility and sensitivity. The drug was discovered by SmithKline Beecham plc, and Alizyme acquired full rights prior to SKB's merger with GlaxoWellcome plc.
Palmer said he is optimistic on finding a partner for renzapride, noting that there are not many products around at this stage of development. He hopes to find a licensee by mid-2004, when the drug will be ready for Phase III. "We can't afford to do Phase III by ourselves, but it doesn't cost anything to do the preparation."
Alizyme has enough money to last until the end of 2004, having raised £16.1 million (US$25.6 million) in a placement in January. The company also has Colal-Pred for the treatment of ulcerative colitis in Phase III, and ATL-104, a lipase inhibitor for treating obesity, in Phase IIb, both ready to license. "We ought to get something before the money runs out," Palmer said.