Pentosan polysulfate sodium highly effective in treating interstitial cystitis, increased symptom relief suggested with continued therapy

-- Patients report significant symptom relief as early as four weeks into treatment --

ANAHEIM, Ca., June 3, 2001 � Interstitial cystitis (IC) patients taking pentosan polysulfate sodium (Elmiron�) experienced increased symptom relief with continued therapy, according to the results of a study presented today at the 96th Annual American Urological Association Meeting. Moreover, of patients completing the study, 67 percent assigned to the recommended 300 mg dose of Elmiron responded favorably, with patients assigned to higher doses reporting similar symptom improvement. All those completing the study reported symptom relief starting as early as four weeks and increasing steadily over the course of treatment from baseline.

"This is the first study to evaluate onset of effect and dose-response relationship in patients treated with Elmiron," said lead study investigator J. Curtis Nickel, M.D., of Queens University in Kingston, Ontario. "We were pleased to find that not only did symptoms improve for many patients as early as four weeks into treatment, but also that the majority of patients experienced increased symptom relief as the study progressed -- regardless of dose. These results are good news for IC patients, because they confirm the efficacy of Elmiron and suggest that even further improvements may be obtained with prolonged treatment."

Interstitial cystitis (IC) is a chronic, progressive and frequently painful bladder condition, the cause of which is unknown. IC affects hundreds of thousands, perhaps millions, of people in the United States, 90 percent of whom are women. Symptoms include the urgent and frequent need to urinate (day and night) and pain in the bladder and pelvic area. These symptoms may create substantial psychological and social problems. In addition, pain and sleep loss associated with IC can lead to depression.

Elmiron is the only oral medication approved by the U.S. Food and Drug Administration for treating IC symptoms. Other treatments include invasive procedures that instill medication directly into the bladder. The recommended dose of Elmiron is 300 mg/day, taken as one 100 mg capsule, three times daily. Elmiron structurally and chemically resembles the glycosaminoglycans, or "GAG layer," which lines the bladder. Although the exact mechanism of action for the drug is unknown, it is believed to strengthen the bladder�s protective layer and act as a buffer, preventing irritating fluids from reaching the urinary tract lining.

Study Design
Three hundred eighty patients with a positive cystoscopic exam or history of IC symptoms �6 months, were randomized to receive 100, 200, or 300 mg of pentosan polysulfate sodium three times daily (total daily doses of 300, 600 or 900 mg, respectively). Response was measured by the IC Symptom Index (ICSI), on which a score of 0 means no symptoms and 20 means symptoms almost always, and the Patient�s Overall Rating of Improvement of Symptoms (PORIS), on which patients with a score of 50 to 100 percent were considered responders. Investigators obtained measurements at baseline, four, eight, 12, 16, 24 and 32 weeks of treatment and recorded adverse events during follow-up visits. Response to treatment was assessed in patients who completed the trial as well as in the intent-to-treat group.

Study Results
Investigators observed statistically significant improvements from baseline to endpoint in mean ICSI scores for all dosages (p<0.001), with signs of continuously increasing response rates beyond 32 weeks. A majority of the 230 patients who completed the trial were responders (67.1 percent, 59.5 percent and 60.1 percent for the 300, 600 and 900 mg dosages, respectively), with only 4.5 percent discontinuing due to lack of efficacy. Within four weeks, 20 percent to 26 percent of all patients were classified as responders (�50% improvement on PORIS) and this percentage increased over time. At 32 weeks, 49.6 percent, 49.6 percent and 45.2 percent of all patients who began the trial were responders on 300, 600, and 900 mg, respectively. Responses to increased dosages, as measured by the study endpoints, were not statistically different. Diarrhea (25.3 percent), headache (18.2 percent) and nausea (15.0 percent) were among the most common adverse events.

This study was sponsored by ALZA Corporation.