Glaxo will try to expand the Lotronex (alosetron) market to men, adolescents and children, following the Feb. 9 approval of the irritable bowel syndrome treatment for use in women whose predominant IBS symptom is diarrhea.

Glaxo is currently evaluating the effectiveness of the Phase IIb 5-HT3 receptor antagonist in men; dose-ranging studies in men, testing four different dosage strengths, began in fourth quarter 1999. Results are expected by the end of the year, Glaxo said.

The company initially chose to move forward with the women-only indication when Lotronex showed "preferential" efficacy in Phase II trials. Early Lotronex studies had found plasma concentrations to be 30%-50% "lower and less variable" in men compared to women given the same oral dose.

Studies of the product in adolescents have also been initiated, Glaxo said. The firm will likely begin pediatric efficacy studies in the spring; Glaxo submitted a pediatric study proposal and expects an FDA response in early March. Pharmacokinetic studies in children are also set to begin imminently.

Even with the narrowed indication of treatment for females whose predominant IBS symptom is diarrhea, the potential market for Lotronex is large: Glaxo estimates that more than 30 mil. U.S. women suffer from diarrhea-predominant IBS.

Even if Glaxo reaches only a small portion of the female IBS market, Lotronex would be a multibillion dollar product. The average wholesale price of Lotronex is $1.98 per tab and the product will be available in 60-count bottles. Based on the $2 per pill price tag and twice daily dosing, one year of therapy per patient would cost $1,445.

Seventy percent of irritable bowel syndrome sufferers are women, Glaxo estimates. The diarrhea predominant form occurs in 32%-47% of total IBS sufferers, but in women the number could reach 58%, Glaxo suggested.

A slightly smaller percent of the total IBS population is thought to suffer from the constipation-predominant form of the disease, and a slightly larger number from a form that alternates between diarrhea and constipation.

Glaxo had originally sought the alternating symptomology indication as well as the diarrhea-predominant indication for Lotronex, but FDA's Gastrointestinal Drugs Advisory Committee recommended against approval for the alternative IBS symptoms indication due to the increased risk for constipation associated with the drug (¹ Also see "Glaxo Lotronex Indication Would Cover One-Third Of IBS Patients" - Pink Sheet, 22 November, 1999.).

Glaxo is currently enrolling 600 alternating IBS patients in an additional trial to re-evaluate efficacy in that population. Results are expected by early 2001. The company is also studying Lotronex use in combination with laxatives to control the constipation side-effect, as well as additional constipation management studies.

Commercial launch of the product in March will be followed by a direct-to-consumer print and broadcast advertising campaign, managed by Jordan McGrath Case & Partners (New York).

Glaxo reps have already begun the process of educating physicians about irritable bowel disease, Glaxo reported, and will begin detailing physicians shortly after an early-March launch meeting.

The product will be supported, at least initially, by Glaxo's sales force rather than by a combined Glaxo/SmithKline Beecham force.

Although Glaxo previously touted the power of a close to 8,000-rep combined sales force from the company's ongoing merger with SB, more recent announcements indicate that the Glaxo and SmithKline sales and marketing components in the U.S. will remain separate during the first phases of the merger process (² Also see "Glaxo SmithKline Taking Soft Merger Route: Will Start With Two U.S. Heads" - Pink Sheet, 7 February, 2000.).

Glaxo is already starting to focus on the social impact of IBS and is likely to include quality-of-life data in its consumer promotion efforts for Lotronex.

"Irritable Bowel Syndrome in American Women: A Landmark Survey," conducted and disseminated by the firm, describes social implications of the disease. For example, 33% of women with IBS avoid group outings, 28% report that IBS limits their sex life and 43% report that social activities, sporting activities and vacations are limited by the condition.

Any consumer effort is likely to be accompanied by patient testimonials similar to Pharmacia & Upjohn's promotions for Detrol that have popularized the concept of "overactive bladder" in incontinence. P&U is projecting Detrol could become a $1 bil. product with an approval for once-daily dosing (³ Also see "Detrol Sales Potential Could Be $1 Bil. With Once-Daily Indication, P&U Says" - Pink Sheet, 14 February, 2000.).

Approval was based on two 12-week double-blind studies in 1,273 female patients. "In both trials, Lotronex 1 mg administered twice daily was significantly more effective than placebo in providing relief of IBS pain and discomfort," labeling states.

Treatment resulted in a "significant decrease in the percentage of days with [bowel] urgency as compared to those who received placebo" and "resulted in firmer stools and a significant decrease in stool frequency."

The most commonly reported side effect of Lotronex treatment was constipation (28% vs. 5% placebo). Nausea (7% Lotronex vs. 6% placebo) and gastrointestinal discomfort and pain (5% vs. 6%) were also reported.

Lotronex labeling also contains a warning about acute ischemic colitis. The condition "was infrequently reported" in clinical trials, labeling states, noting that "a casual association between treatment with Lotronex and acute colitis has not been established, nor have risk factors been identified."

No cases of ischemic colitis were reported in Glaxo's 12-month long-term safety study, labeling adds.

Physicians are instructed to discontinue Lotronex therapy if patients experience rectal bleeding and suffer worsening of abdominal pain.

Glaxo will evaluate the relationship between Lotronex use and acute ischemic colitis in a large post-marketing epidemiological study.

Glaxo submitted the Lotronex NDA for priority review in June 1999; the six-month deadline was later extended by three months to accommodate Glaxo's submission of additional safety information following the advisory committee review.

Lotronex is also in Phase II development for other gastrointestinal indications, including non-ulcer dyspepsia and "dumping syndrome."

Glaxo Lotronex Studies May Expand Market To Men, Teens, Pediatrics

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