These new data show that after 12 weeks treatment with darifenacin, people with OAB symptoms are more able to undertake household tasks, socialise, work and travel. They are also less likely to feel depressed, anxious or nervous, as demonstrated by improvements in the King's Health Questionnaire (a questionnaire designed to assess the impact of bladder problems on patient's quality of life).
"OAB symptoms can severely restrict people's lives. People with OAB find urgency - a sudden compelling desire to pass urine, which is difficult to defer - to be particularly bothersome. Less mobile people find this hard to cope with, as they require greater time to reach a toilet. This can cause patients to avoid leaving their home, which severely restricts their lives and can result in social isolation and depression," said Con Kelleher, Consultant in Obstetrics and Gynaecology at Guy's and St Thomas' Hospitals Trust, London, UK. "These new data show that darifenacin significantly improved the quality of life for people with OAB, enabling them to resume everyday activities and lead less restricted lives."
Today's data also highlight darifenacin's tolerability and safety; as central nervous system (CNS) and cardiovascular (CV) safety were comparable to placebo.1 Recent reports provide emerging evidence, however, that current marketed treatments may create CNS problems such as cognitive impairment, due to a blockade of the M1 muscarinic receptor, and somnolence (unnatural drowsiness).3,4,5
Anti-cholinergics are the treatment of choice for OAB and act on receptors that activate the detrusor muscle to achieve bladder control. Symptoms of OAB are urinary urgency, with or without urge incontinence (strong desire to empty the bladder with an involuntary loss of urine), urinary frequency (emptying the bladder eight or more times in 24 hours), and nocturia (awakening two or more times a night to empty the bladder). Darifenacin is a new M3 selective receptor antagonist in development for OAB, which is proven to reduce the number of weekly incontinence episodes by up to 77%.6 The main treatment-related effects were noted as being constipation and dry mouth that resulted in low discontinuation rates.
Regulatory applications for Enablex®/Emselex® (darifenacin hydrobromide) have been submitted to the US and European authorities for the once daily oral treatment of overactive bladder in doses of 7.5mg and 15mg. On 3 October 2003, the company received an approvable letter from the US Food and Drug Administration. Novartis expects approval of Enablex/Emselex globally in 2004.
This release contains certain forward-looking statements relating to Novartis Pharma AG's business, which can be identified by the use of forward-looking terminology, such as "new", "first" and "may" or similar expressions, or by discussions of strategy, plans or intentions. Such forward looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results to be materially different from any future results, performance, or achievements expressed or implied by such statements. Commercialisation can be affected by, amongst other things, uncertainties relating to regulatory actions or delays or government regulation generally, the ability to obtain or maintain patent or other proprietary intellectual property protection and competition in general, as well as factors discussed in the Company's Form 20F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialise, or should underlying assumptions prove incorrect, actual results may vary materially from those described therein as anticipated, believed, estimated or expected.
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Notes to editors
Results are from a pooled analysis of three multicentre, double-blind, placebo-controlled studies. The pooled population comprised 1,059 adults with OAB symptoms for more than 6 months. Patients were randomised to 12 weeks once daily treatment darifenacin 7.5mg and matching placebo or once daily darifenacin 15mg and matching placebo. Quality of life (QoL) was assessed at baseline and study end using the OAB-specific King's Health Questionnaire (KHQ), decreasing score representing improved QoL. Disease-specific questionnaires are more beneficial in evaluating the impact of specific lower urinary tract symptoms on QoL and are more sensitive than their generic counterparts in detecting changes as a result of treatment.
| KHQ domain | Darifenacin 7.5 mg | Darifenacin 15 mg | Placebo | ||
|---|---|---|---|---|---|
| Mean change from baseline | Adjusted mean difference from placebo | Mean change from baseline | Adjusted mean difference from placebo | Mean change from baseline | |
| Incontinence impact | –23.2 | –12.9* | –20.9 | –10.4* | –9.6 |
| Emotions | –14.3 | –5.4* | –14.0 | –5.8* | –7.6 |
| Social limitations | –14.2 | –7.4* | –14.0 | –7.9* | –5.0 |
| Role limitations | –24.5 | –11.2* | –23.5 | –10.8* | –12.2 |
| Physical limitations | –20.3 | –6.5* | –20.9 | –7.7* | –13.3 |
| Personal relationships | –7.2 | –4.0 | –5.6 | –2.2 | –4.0 |
| Sleep and energy | –9.0 | –3.5 | –10.0 | -3.1 | –7.6 |
| Severity measures | –11.5 | –7.4* | –13.2 | –9.0* | –4.9 |
| General health | –1.6 | 0.7 | –0.8 | –0.8 | –0.2 |
*p <0.01 vs placebo.
References
1. "Darifenacin, an M3 Selective Receptor Antagonist, Improves Quality of Life on Patients with Overactive Bladder" Chapple C, Kelleher C, Perrault L, poster presented at World Health Organisation's 3rd International Consultation on Incontinence, Monte Carlo.
2. Milsom I et al. The prevalence of overactive bladder. Am J Manag Care. 2000;6(Suppl 11):S565-S573
3. "Darifenacin, an M3 selective receptor antagonist for the treatment of overactive bladder, does not affect cognitive function in elderly volunteers" Lipton R, Kolodner K, Wesnes K, Edgar C, poster presented at X1Xth European Association of Urology (EAU) Congress, Vienna
4. Katz IR et al. Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc. 1998 Jan;46(1):8-13
5. Womack FB, et al. Tolterodine and Memory Dry but Forgetful. Arch Neurol 2003;60:771-3
6. "Darifenacin is effective in improving the major symptoms of overactive bladder: a pooled analysis of phase III studies" C Chapple, poster presented at X1Xth European Association of Urology (EAU) Congress, Vienna