The url for this article is: http://www.medscape.com/reuters/prof/2000/...128drgd003.html Novartis' Zelmac Shows Efficacy in Phase III Studies --------------------------------------------------------------------------------LONDON (Reuters Health) Nov 28 - Swiss pharmaceuticals group Novartis now has all the data needed for marketing approval in 2001 of Zelmac (tegaserod) for the treatment of irritable bowel syndrome, company researchers said on Tuesday. Although the US Food and Drug Administration (FDA) issued an approvable letter in August for using the drug in women with the constipation-predominant form of the disease, it also made clear that final approval would not be granted without additional trial results after one of the three pivotal studies failed to show statistical significance. Novartis Clinical Research Manager Dr. Godeleive Vandeplassche said that preliminary analysis of a fourth phase lll study of 1500 women had now confirmed that the 5HT4 receptor agonist was safe and effective. She told Reuters Health during the European Digestive Disease meeting in Brussels that the new data would be submitted next month to the FDA in time for a product launch in the US in mid-2001. The drug is also awaiting centralised approval in Europe, where the firm hopes to launch the drug in the third of or fourth quarter of 2001. It will be co-promoted by Bristol-Myers Squibb in all countries, except Japan, with a combined global sales force of more than 6,000, company executives said. They added that they were confident of finding clinical and cost-effectiveness data to satisfy the UK's National Institute for Clinical Excellence, even though in trials the drug has proved only about 10% better than the often substantial improvement seen in patients on placebo. Gastroenterologists said that they expect Zelmac will prove intrinsically safer than Glaxo Wellcome's drug for the diarrhea-predominant form of IBS, Lotronex (alosetron), which has been linked with 70 reports of adverse events, five fatal, since being launched in the US in March. Dr. Robin Spiller, from the University of Nottingham in the UK, pointed out that there was no risk of making constipation worse with Zelmac. He added, "It is amazing to think that alosetron has been out in the US for 8 months and they have already sold 450,000 scripts. "Marketing has become so efficient. Instead of starting slowly and building up, they are starting with a bang. That is good for the company selling the drugs, but it is bad because they get tremendous exposure to the adverse effects." Dr. Sidney Phillips, from the Mayo Clinic in Minnesota, said that tegaserod and alosetron offered considerable benefit in treating the multiple symptoms of IBS but stressed that many patients could be treated without any drugs at all. Dr. Spiller agreed that many patients only needed reassurance or to change their diet. Others sometimes benefited from anti-depressants and psychotherapy. Results of a placebo-controlled study of 799 patients presented at the meeting showed that a daily dose of 12 mg tegaserod relieves abdominal pain from the second day of treatment. Relief of bloating improved during the first week and bowel function improved from day one. This rapid onset of action increases the chances of patient compliance, said Dr. Joerg Reinhardt, global head of development at Novartis. Results of a smaller study also showed that tegaserod is well-tolerated in patients with diarrhoea-predominant IBS and does not cause any significant safety problems such as dehydration and electrolyte abnormalties. Although the drug is not indicated for this type of IBS, company researchers explained that the finding is important because many patients with constipation-predominant IBS also experience occasional bouts of diarrhoea. Zelmac's potential market might therefore be larger than the market for Lotronex. Dr. Christoph Beglinger, from the University Hospital in Basel, Switzerland, said that the phase lll studies showed that Zelmac was well-tolerated. The only adverse event related to drug treatment was diarrhoea--and this was short lived, causing only 1.6% of patients to discontinue treatment. He said that the trial results had failed so far to show any significant benefit in male patients, though why the drug should work only in women was not understood.