Urinary Incontinence
Urinary Incontinence: New options for an emerging therapeutic market

Therapeutic

This invaluable publication supplies in-depth information, market values and forecasts on recently launched drugs, and drugs in clinical and preclinical development for the treatment of incontinence. It also provides advice on target areas for the development of new therapeutic products.

Urinary Incontinence: New options for an emerging therapeutic market will provide the information you need when investing in incontinence R&D.

If you need to know�

then Urinary Incontinence is the report for you.

This invaluable publication will enable you to:

Scrip's Incontinence report will supply you with a comprehensive basis for the development of your own business plan, and help you bridge the gap between the R&D and marketing interface.

PUBLISHED: SEPTEMBER 2000
REF: BS1079E
PAGES: 100
PRICE: £395/$830/¥95,000

TABLE OF CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY

CHAPTER 1 INTRODUCTION TO URINARY INCONTINENCE
1.1 Definition and background
1.2 The bladder and its function
1.2.1 Anatomical and physiological features
1.2.1.1 The control of urine flow
1.3 Causes of urinary incontinence
1.4 Risk factors for urinary incontinence
1.5 Types of incontinence
1.5.1 Stress incontinence
1.5.2 Urge incontinence
1.5.3 Overflow incontinence
1.5.4 Functional incontinence
1.6 Urinary incontinence and ageing
1.6.1 Urinary incontinence in children
1.7 Complications from urinary incontinence

CHAPTER 2 CURRENT MANAGEMENT OF URINARY INCONTINENCE
2.1 Options for management
2.2 Evaluating incontinence
2.2.1 Physical examination
2.2.2 Diagnostic tests
2.2.2.1 Simple tests
2.2.2.2 Urodynamics
2.2.2.3 Imaging techniques
2.2.2.4 Cytoscopy
2.3 Treatment
2.3.1 Non-surgical treatments
2.3.1.1 Behavioural options
2.3.2 Surgical treatment
2.3.2.1 Colposuspension
2.3.2.2 Pubovaginal sling
2.3.2.3 Tension-free vaginal tape
2.3.2.4 Bladder neck injections
2.3.3 Devices
2.3.3.1 Pelvic organ support device
2.3.3.2 Urinary control inserts
2.3.3.3 Artificial urinary sphincter
2.3.3.4 Incontinence clamp
2.3.3.5 Sacral nerve stimulation
2.3.3.6 Magnetic stimulation
2.3.3.7 Catheters
2.3.3.8 Absorbent products
2.3.4 Pharmacological treatment
2.3.4.1 Antimuscarinic/anticholinergic drugs
2.3.4.2 Tricyclic antidepressants
2.3.4.3 Desmopressin
2.3.5 Management recommendations from the International Consultation on Incontinence
2.3.5.1 Children
2.3.5.2 Men
2.3.5.3 Women
2.3.5.4 Neurogenic incontinence
2.3.5.5 The frail and elderly

CHAPTER 3 NEW AND EMERGING STRATEGIES FOR MANAGING URINARY INCONTINENCE
3.1 Introduction
3.2 Recently launched drugs
3.2.1 Ditropan XL
3.2.1.1 Clinical trials with Ditropan XL
3.2.1.2 Marketing of Ditropan XL
3.2.1.3 Sales potential
3.2.1.4 Incontinence pad cost savings with Ditropan XL
3.2.1.5 The OBJECT Trial
3.2.1.6 Improving oxybutynin tolerability
3.2.2 Tolterodine
3.2.2.1 Clinical trials
3.2.2.2 Side effects
3.2.2.3 Tolterodine treatment and elderly patients
3.2.2.4 The National Overactive Bladder Evaluation Study
3.2.2.5 Sales potential
3.2.2.6 Detrol XL
3.3 Drugs in late clinical development
3.3.1 Duloxetine
3.3.2 Darifenacin
3.3.3 (S)-oxybutynin
3.3.4 Oxybutynin transdermal patch
3.3.5 Temiverine hydrochloride
3.4 Targets for new drug development
3.4.1 Centrally acting drugs
3.4.2 Peripheral targets
3.4.2.1 Calcium channel antagonists
3.4.2.2 Potassium channel openers
3.4.2.3 a-Adrenergic antagonists
3.4.2.4 b-Adrenergic agonists
3.4.2.5 Prostaglandin synthesis inhibitors
3.4.2.6 Phosphodiesterase inhibitors
3.4.2.7 Tachykinins
3.5 Drugs in early clinical development
3.5.1 HCT-1026
3.5.2 YM-905
3.5.3 NS-49
3.5.4 ESR-150
3.5.5 TAK-637
3.5.6 SB-223412
3.5.7 LY-353433
3.5.8 ZD-0947
3.5.9 Resiniferatoxin
3.5.10 Oxybutynin topical patch
3.6 Drugs in preclinical development
3.6.1 AH-9700
3.6.2 SPM-007
3.6.3 NS-8
3.6.4 KW-7158
3.6.5 Ion channel-modulating-drugs
3.6.6 GS-332
3.6.7 Controlled-release formulation of oxybutynin
3.6.8 Gene therapy with insulin-like growth factor
3.6.9 Gene therapy using nerve growth factor
3.7 Intravesical therapy
3.8 Conclusion

CHAPTER 4 URINARY INCONTINENCE DRUG TREATMENT MARKET: EPIDEMIOLOGY AND MARKET VALUE
4.1 Introduction
4.2 Prevalence of urinary incontinence
4.3 Epidemiological studies
4.4 The size of the market
4.4.1 Size of the market in the US
4.4.2 Size and structure of the market in Europe
4.4.2.1 Size and structure of the market in the UK
4.4.2.2 Other European studies
4.4.3 The size of the market in Japan
4.5 The market for drugs to treat urinary incontinence
4.6 Pharmacia & Upjohn's marketing strategy for tolterodine
4.6.1 Direct-to-consumer advertising in the UK

CHAPTER 5 COMPANY PROFILES
5.1 Afferon Corporation
5.1.1 The company
5.2 Alza Corporation
5.2.1 The company
5.2.2 Agreements regarding urinary incontinence products
5.2.3 Financial highlights
5.2.4 Drugs marketed for urinary incontinence
5.3 Interneuron Pharmaceuticals Inc
5.3.1 The company
5.3.2 Financial highlights
5.3.3 Drugs in development for urinary incontinence
5.4 NicOx SA
5.4.1 The company
5.4.2 Financial highlights
5.4.3 Drugs in development for urinary incontinence
5.5 Nippon Shinyaku Co Ltd
5.5.1 The company
5.5.2 Financial highlights
5.5.3 Drugs in development for urinary incontinence
5.6 Pfizer Inc
5.6.1 The company
5.6.2 Financial highlights
5.6.3 Drugs in development for urinary incontinence
5.6.4 Pfizer�Warner-Lambert merger
5.7 Pharmacia & Upjohn Inc
5.7.1 The company
5.7.2 Financial highlights
5.7.3 Drugs for marketed urinary incontinence
5.8 Sanofi-Synth�labo
5.8.1 The company
5.8.2 Financial highlights
5.8.3 Drugs in development for urinary incontinence
5.9 Schwarz Pharma AG
5.9.1 The company
5.9.2 Financial highlights
5.9.3 Drugs in development for urinary incontinence
5.10 Sepracor Inc
5.10.1 The company
5.10.2 Financial highlights
5.10.3 Drugs in development for urinary incontinence
5.11 Yamanouchi Pharmaceutical Co Ltd
5.11.1 The company
5.11.2 Financial highlights
5.11.3 Drugs in development for urinary incontinence

REFERENCES

LIST OF TABLES

Table 1.1 Types of urinary incontinence
Table 2.1 Drugs launched for the treatment of urinary incontinence
Table 2.2 Drugs available in the UK for the treatment of urinary incontinence
Table 3.1 Tolterodine: Phase III clinical trials summary
Table 3.2 Drugs in or about to enter late clinical development
Table 3.3 Drugs categories with potential for the treatment of bladder overactivity and urinary urge incontinence
Table 3.4 Drugs in early clinical development
Table 3.5 Incontinence drugs in preclinical development
Table 4.1 Estimated and projected prevalence of overactive bladder in the US 40+ population, 2000�2010
Table 4.2 Prevalence of urinary incontinence in six European countries in people aged 40+
Table 4.3 Percentage prevalence of overactive bladder by country and age group
Table 4.4 Percentage prevalence of overactive bladder in people aged 40+ by country and gender
Table 4.5 Population and projected population data by country, 2000�2010
Table 4.6 Prevalence of overactive bladder by country, projected from 2000 to 2010
Table 4.7 Prevalence and projected prevalence of overactive bladder in men and women aged 40+ by country
Table 4.8 Prevalence of urinary incontinence in the UK in people aged 40+
Table 4.9 Prevalence of urinary incontinence in a sample of women from an urban Swedish population
Table 4.10 Percentage distribution of incontinence by type, and according to age
Table 4.11 Prevalence of incontinence by type and age group, as a percentage of the whole population sample
Table 4.12 Prevalence of incontinence by age
Table 4.13 Prevalence of urinary incontinence in men and women by age
Table 4.14 Prevalence of urinary incontinence in a Spanish population sample aged 60+
Table 4.15 Prevalence of urinary incontinence: an Austrian study
Table 4.16 Age distribution of study sample
Table 4.17 Urinary incontinence in Japanese men
Table 4.18 Urinary incontinence in Japanese women
Table 4.19 Population data for Japanese men and women aged 40�70+ years, 2000�2010
Table 4.20 Estimated prevalence of urge, stress or mixed incontinence in men aged 40�70+ years, projected to 2010
Table 4.21 Estimated prevalence of urge, stress or mixed incontinence in women aged 40�70+ years, projected to 2010
Table 4.22 Estimated prevalence of urge incontinence (urge + mixed) in men and women aged 40�70+ years, projected to 2010
Table 4.23 Estimated and projected market size for drugs to treat urge incontinence in Japan
Table 4.24 Prevalence and types of urinary incontinence in a sample of Japanese women attending a gynaecology outpatient clinic
Table 4.25 Sales and projected sales of drugs to treat urinary incontinence ($ million) 1998�2002 and peak sales projections to 2008
Table 4.26 Drugs in development for the treatment of urinary incontinence, and market projections
Table 5.1 Alza's Financial highlights ($ million), 1996�1999
Table 5.2 Alza's geographic distribution of sales ($ million), 1997�1999
Table 5.3 Alza's urology business unit products
Table 5.4 Interneuron Pharmaceutical's Financial highlights ($ thousand), 1996�1999
Table 5.5 Selected financial data for NicOx SA ($ thousand), 1996�1999
Table 5.6 Nippon Shinyaku's financial highlights ($ million), 1996�1999
Table 5.7 Nippon Shinyaku's pharmaceutical sales by product ($ million), 1998�1999
Table 5.8 Drugs in development by Nippon Shinyaku for urinary incontinence
Table 5.9 Pfizer's financial highlights ($ million), 1996�1999
Table 5.10 Pfizer's sales by geographical area ($ million), 1996�1999
Table 5.11 Pharmacia & Upjohn's financial highlights ($ million), 1996�1999
Table 5.12 Pharmacia & Upjohn's sales by region($ million), 1997�1999
Table 5.13 Sanofi-Synth�labo's sales by therapeutic area, 1999
Table 5.14 Sanofi-Synth�labo's sales by geographic area, 1999
Table 5.15 Schwarz Pharma's financial highlights ($ million), 1996�1999
Table 5.16 Schwarz Pharma's sales by markets ($ million), 1997�1999
Table 5.17 Sepracor's financial highlights ($ million), 1996�2000
Table 5.18 Yamanouchi's financial highlights ($ million), 1996�2000
Table 5.19 Yamanouchi's sales by region ($ million), 1999�2000

LIST OF FIGURES

Figure 1.1 The Bladder
Figure 2.1 Muscarinic receptors and ß-adrenoceptors regulate bladder tone and contraction in overactive bladder.
Figure 2.2 Pharmacotherapy for overactive bladder
Figure 2.3 Initial management of urinary incontinence in children
Figure 2.4 Initial management of urinary incontinence in men
Figure 2.5 Initial management of urinary incontinence in women
Figure 2.6 Initial management of neurogenic urinary incontinence
Figure 2.7 Initial management of urinary incontinence in frail disabled elderly people
Figure 3.3 Sales of Ditropan, Ditropan XL, Detrol & other brands, 1999�2000
Figure 4.1 Prevalence of overactive bladder in Europe by age group
Figure 4.2 Sales and projected sales of Ditropan XL and Detrol worldwide 1998�2002, and estimated peak sales

EXECUTIVE SUMMARY

The World Health Organisation (WHO) estimates that the direct and indirect costs of urinary incontinence exceed $16 billion annually. However, demographic changes resulting in greater numbers of elderly people at risk from the condition could increase this figure to around $30 billion annually within the next 10 years.

Urinary incontinence has not, until now, been regarded as an important pharmaceutical market, mainly because only a small proportion of the 200 million sufferers worldwide currently receive drug treatment. The products available have, until recently, tended to be off-patent, and their high profile of undesirable side effects has meant that many users are unable to tolerate them. However, the situation is changing, and urinary incontinence is now seen by drug companies as a vast, although largely unexplored, market, and a major opportunity for drug development. The recent introduction of new and improved antimuscarinic drugs, the implementation of patient awareness campaigns, and the direct-to-consumer advertising push launched by two leading companies, is expected to encourage patients to seek medical help. Moreover, although urinary incontinence is not necessarily age-related, elderly people tend to be more susceptible to it, and as a result, an ageing population will lead to an increase in the prevalence of the condition, and a greater demand for treatment.

Urinary incontinence is defined by the International Continence Society as a condition in which the involuntary loss of urine can be demonstrated objectively, and which causes a social or hygiene problem. It is surprisingly common, and although not life-threatening, it can be very distressing and seriously impact on an individual's emotional, psychological and social well-being, thereby compromising his or her quality of life. Furthermore, where elderly people are involved, it is a burden for family and community care workers, and is one of the main reasons why ageing relatives are put into nursing homes.

In 1998, the WHO raised the profile of urinary incontinence and reclassified it as a disease rather than a condition. As such, it is more likely to be taken seriously, and this is expected to raise awareness of its symptoms, treatment and prevention. Many people with urinary incontinence suffer in silence because they are embarrassed, and many do not seek help because they do not know that it can be treated. When the problem is discussed, patients are often told, incorrectly, that it is a normal consequence of ageing and they should learn to live with it. As people become aware of opportunities for treatment, however, so they will become more demanding. Within the next decade, there is expected to be a marked alteration in attitudes towards urinary incontinence, and a significant increase in the number of individuals seeking help. This will have a major impact on the market.

There are several types of urinary incontinence, the two most common ones being stress incontinence, which affects mainly women, and urge incontinence, which affects both men and women more or less equally. A third type of incontinence, known as overflow incontinence, usually affects men, and is frequently associated with an enlarged prostate gland. Both stress incontinence and overflow incontinence can co-exist with urge incontinence. Urge incontinence is part of a complex of lower urinary tract symptoms known as unstable, or unstable bladder, which include symptoms of frequency and/or urgency with or without urge incontinence. It can be treated with drugs, whereas stress and overflow incontinence, if not rectified by behavioural therapy, are usually treated surgically or managed with the aid of a suitable device.

The interest of the pharmaceutical industry is focused on the treatment of overactive bladder with or without urge incontinence. However, treatment of stress incontinence with a-adrenergic stimulants is now being considered, as is treatment of overflow incontinence using a-adrenergic blockers eg Prazosin (Invicta) and Alfuzosin hydrochloride (Sanofi-Synth�labo).

A significant breakthrough in the pharmacological treatment of urinary incontinence came with the launch of two new products. Pharmacia & Upjohn's new anticholinergic drug tolterodine (Detrusitol/Detrol) is now taking over from generic preparations of oxybutynin in the US, mainly because it has a lower side effect profile. In addition, older drugs have been revamped to try and circumvent the annoying side effects caused by the non-specific nature of the drugs. Alza has introduced a once-daily sustained-release version of oxybutynin (Ditropan XL) which is claimed to have a 50% lower incidence of severe dry mouth, one of the major side effects of anticholinergic drugs. It is expected to not only replace generic oxybutynin, but also to compete with tolterodine for a share of the market.

Considerable R&D is under way to develop effective drugs with superior efficacy and fewer adverse events. Products in development include Pfizer's specific muscarinic antagonist, darifenacin (a single-isomer version of the oxybutynin racemate), a transdermal oxybutynin patch, neurokinin antagonists and nitric oxide modulators. Companies are also looking at alternative routes of delivery for existing drugs.

Less than 20% of people with urge or mixed incontinence receive drug treatment, and the total worldwide market, currently estimated at around $500 million for drugs, contrasts markedly with the $1.5 billion spent on incontinence pads in the US alone in 1999. Lehman Brothers predict drug sales of $700 million in 2000 rising to $1.1 billion in 2002. Thus the market is wide open and there is plenty of room for growth.

© PJB Publications Ltd. 2001
All rights reserved.