FDA APPROVES GLAXO WELCOME'S LOTRONEX FOR IRRITABLE BOWEL.

Relief may be in sight for millions of women who suffer from one of the most prevalent yet least understood medical conditions in the United States -irritable bowel syndrome (IBS). The Food and Drug Administration has approved the medicine Lotronex(TM) (alosetron hydrochloride) for use in treating females with irritable bowel syndrome who suffer from IBS-associated abdominal pain and discomfort, and for whom diarrhea is a primary symptom.

Lotronex, a potent and selective 5-HT3 antagonist, is the first of a new generation of agents being studied specifically for the treatment of IBS to receive FDA approval. Lotronex also becomes the first new treatment for IBS to enter the marketplace in many years and is the first medicine in the U.S. proven in well controlled, large clinical trials to address multiple symptoms of the condition.

"With the approval of Lotronex, physicians have something to offer many of their female IBS patients that can provide relief from IBS pain and discomfort, and some bowel-related symptoms," said Dr. Eugene Burbige, chairman of the gastroenterology division at Mt. Diablo Medical Center in Concord, California. "Current treatment options for IBS are widely considered to be limited and generally address a single symptom of the condition."

More Americans suffer from IBS than asthma or diabetes. IBS is a chronic medical condition that affects an estimated one in five adult Americans and three times as many women as men. IBS is the most common gastrointestinal diagnosis among gastroenterology practices in the U.S. and is one of the top ten most frequently diagnosed conditions among U.S. physicians. IBS is characterized by multiple symptoms that include chronic, recurrent abdominal pain and discomfort, and irregular bowel function such as diarrhea, constipation or alternating diarrhea and constipation.

While the precise mechanism of action for Lotronex is not yet fully understood, one hypothesis is that Lotronex blocks the action of serotonin at 5-HT3 sites in the enteric nervous system. The neurotransmitter serotonin and 5-HT3 receptors that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations, are thought to play a role in increasing the sensation of pain and affecting bowel function in patients with IBS.

Today's approval of Lotronex was based on data from two large phase III clinical trials that were evaluated by the FDA as part of the New Drug Application (NDA). Data from these studies showed that Lotronex was superior to placebo in providing relief of IBS pain and discomfort, decreasing urgency (the sudden feeling of having to go to the bathroom), and reducing stool frequency in females with diarrhea predominant IBS. Relief of IBS pain and discomfort occurred by the end of the first week of treatment in one study and the end of the fourth week of treatment in the second study. Improvements in bowel function in both studies were seen after one week of treatment and continued throughout the 12-week treatment periods. By one week following discontinuation of the drug, symptoms returned. Efficacy beyond twelve weeks has not been established. Safety and effectiveness in men have not been determined.

Data from the clinical trials show that Lotronex is generally well tolerated with the most commonly reported side effect being constipation (28 per cent with Lotronex, five per cent with placebo). Lotronex should not be used in IBS patients who are currently constipated or whose predominant bowel symptom is constipation. Infrequent cases of acute ischemic colitis were reported among patients receiving Lotronex in clinical trials; however, a causal relationship between acute colitis and treatment with Lotronex has not been established. Other side effects reported in the studies included nausea (seven per cent with Lotronex, six per cent with placebo) and gastrointestinal discomfort and pain (five per cent with Lotronex, four per cent with placebo).

"Since taking Lotronex, I now have more freedom to do many of the things that I enjoy doing. I can go out with my husband for the evening. I can walk the dog. I can go to work with more confidence, and be less worried about having the symptoms and problems I had before Lotronex," said Janet Mabrey, an IBS patient who received Lotronex in the phase III clinical trials.

The NDA for Lotronex was submitted to the FDA on June 30, 1999, and was filed by the agency on August 29 with a priority review designation. Products assigned for priority review by the FDA are those which appear to represent a potential therapeutic advance over existing therapies.

Lotronex will be available as one milligram tablets with a labeled dosing recommendation of one tablet twice daily. Lotronex is expected to be available by prescription only in mid-March.

"For millions of women, many of whom have endured the symptoms of IBS in silence, Lotronex will help better manage their condition," said George Morrow, president and CEO of Glaxo Wellcome Inc. "We look forward to the opportunity to work with physicians and patients to bring IBS to the forefront of women's health issues. Lotronex gives sufferers a new reason to discuss IBS symptoms with their physicians."

The new drug submission for Lotronex in Canada was submitted to Health Canada on July 23, 1999. Glaxo Wellcome is presently working with Health Canada towards obtaining Canadian approval of Lotronex.

Glaxo Wellcome is a leader in gastrointestinal research programs. The company is committed to fighting disease by bringing innovative medicines and services to patients throughout the world, and to the health care providers who serve them.

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