Public Release: 

New darifenacin data released at the American Urological Association (AUA)

Enablex significantly reduces overactive bladder symptoms, including incontinence and night-time awakenings, new studies suggest

Ketchum UK

SAN FRANCISCO, CA - May 9, 2004 - Results of two separate Phase III studies involving EnablexTM (darifenacin hydrobromide), an M3 selective receptor antagonist (M3 SRA) being developed for the treatment of overactive bladder (OAB), demonstrated a statistically significant reduction in the frequency of weekly incontinence episodes (up to 77 percent) with Enablex treatment versus placebo. Results from one of the studies (Abstract #5167) also indicate that Enablex reduces the number of weekly nocturnal awakenings due to OAB by 23 percent versus 3.6 percent with placebo. Both were presented today in a plenary session at the Annual Meeting of the American Urological Association (AUA).

"In our study, Enablex-treated patients had a significant reduction in the number of weekly incontinence episodes and the number of times they awoke each night to urinate," said Vik Khullar, MD, Consultant Uro-gynecologist, St. Mary's National Health Service Trust, Imperial College London, UK. "Since nocturia associated with OAB can influence sleep parameters and daytime functioning, Enablex may be an important new treatment option for OAB."

In a second study (Abstract #1528), in addition to reducing the number of incontinence episodes, Enablex improved all efficacy parameters associated with OAB, without central nervous system (CNS) or cardiovascular (CV) safety concerns as compared with placebo.

"Due to its M3 receptor selectivity, Enablex has the potential to provide an effective treatment option with minimal effects on the central nervous and cardiovascular systems," said Christopher Chapple, Consultant Urologist, Royal Hallamshire Hospital, Sheffield, UK. "Furthermore, our results indicate that Enablex significantly reduces the major symptoms of OAB, including incontinence, urination frequency, urge frequency and severity, and bladder capacity."

Acquired by Novartis in 2003, Enablex is an M3 selective receptor antagonist (M3 SRA), which works by selectively blocking the M3 receptor, a primary mediator of detrusor muscle contractility, while sparing the M1 and M2 receptors respectively involved in CNS and CV function. Enablex is currently under review by the US Food and Drug Administration (FDA) for the treatment of overactive bladder. The company received an approvable letter from the FDA in October 2003, and expects to launch the drug in 2004.

Khullar et al conducted a multi-center, double blind study (Abstract #5167) in 439 patients (21-88 years; 85% female) with OAB symptoms for more than six months. In this study, patients treated with Enablex experienced a reduction in the number of weekly nocturnal awakenings (22.1% reduction at 7.5mg and 22.7% reduction at 15 mg) compared with placebo (3.6% reduction), after 12 weeks of treatment. Enablex-treated patients also experienced a decrease in the number of weekly incontinence episodes (68.7 % reduction at 7.5mg and 76.5% reduction at 15mg) as compared with placebo (46.0% reduction).

Data presented (Abstract #1528) by Chapple et al provided an analysis of pooled data from three multi-center, double blind, placebo-controlled studies of Enablex involving 1,049 patients (female 85%, 19-88 years) with OAB symptoms for more than six months. Results at 12 weeks suggest that Enablex (7.5mg and 15mg doses) is superior to placebo in improving all efficacy parameters each week including incontinence episodes (68.4% reduction at 7.5mg and 76.8% reduction at 15mg versus placebo reduction of 54-58%), micturition frequency (16.6% reduction at 7.5mg and 17.4% reduction at 15mg versus placebo reduction of 9-10%), bladder capacity (9.6% increase at 7.5mg and 17.5% increase at 15mg versus placebo increase of 4-5%), urge frequency (29.0% reduction at 7.5mg and 15mg versus placebo reduction of 14-17%), urge severity (14.2% reduction at 7.5mg and 16.1% reduction at 15mg versus placebo reduction of 8%), and incontinence episodes resulting in a change of clothing or pads (77.1% reduction at 7.5mg and 78.6% reduction at 15mg versus placebo reduction of 48-55%). In this analysis, Enablex appeared to be well tolerated; the most common adverse events (dry mouth: 7.5 mg 20%; 15 mg 35%; placebo 8%, constipation: 7.5 mg 15%; 15 mg 21%; placebo 6%) resulted in low rates of discontinuation (7.5 mg 0.6%, 15 mg 2.1%; placebo 0.3%). Central nervous system and cardiovascular adverse events were comparable to placebo.

It is estimated that more than 33 million Americans experience the symptoms of overactive bladder. Caused by the untimely contraction of the detrusor muscle of the bladder, which regulates urination, OAB is characterized by incontinence, urinary urgency and frequency, and nocturia (awakening at night to urinate). According to the American Foundation for Urologic Diseases, at least 16 percent of the population over the age of 40 suffers from chronic and troublesome symptoms of OAB. Although prevalence increases with age, the problem affects people of all ages. As the population becomes increasingly older, the need and hence the market for safe and effective treatments continues to grow.

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Novartis Pharmaceuticals Corporation researches, develops, manufacturers and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG. Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 77,200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

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