Scrip's Complete Guide to Men's Healthcare
Therapeutic

THIS COMPREHENSIVE PUBLICATION COVERS THE MAIN DISEASES AND DISORDERS AFFECTING MEN, INCLUDING:

In each case, the report provides background disease information, including definition, symptoms and diagnosis; details and market values for current treatments and sales potential of future therapeutic products. Also included are profiles of the main companies involved in the growing, profitable field of men's healthcare products.

The information in this therapeutic study will enable you to assess market prospects for current and forthcoming drugs, identify profitable product niches and evaluate your major competitors.

PUBLISHED: June 2000
REF: BS1065E
PAGES: 200
PRICE: £495/$1,040/¥119,000

CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
GLOSSARY AND ABBREVIATIONS


CHAPTER 1 INTRODUCTION
1.1 Men and their health
1.2 Disorders covered by the report
1.2.1 Benign prostatic hyperplasia
1.2.2 Men's cancers
1.2.2.1 Prostate cancer
1.2.2.2 Testicular cancer
1.2.3 Erectile dysfunction
1.2.3.1 The problem
1.2.3.2 Disease management
1.2.4 Androgen replacement therapy
1.2.5 Alopecia
1.2.6 Fertility control
1.2.6.1 Contraception
1.2.6.2 Infertility
1.3 Men's health issues not covered by the report
1.3.1 Suicides in men
1.3.2 Depression, emotion and heart disease
1.3.3 Osteoporosis
1.4 What the future holds
1.4.1 Clinics in English pubs
1.4.2 Government proposals
1.4.3 Market growth


CHAPTER 2 BENIGN PROSTATIC HYPERPLASIA
2.1 Background
2.1.2 Risk factors
2.2 Symptoms
2.3 Diagnosis
2.4 Disease management
2.4.1 Surgical treatment
2.4.1.1 Transurethral surgery
2.4.1.2 Laser surgery
2.4.1.3 Open surgery
2.4.2 Non-surgical treatment
2.4.2.1 Transurethral microwave procedures
2.4.2.2 Transurethral needle ablation
2.4.2.3 Alcohol treatment
2.4.3 Pharmacological management
2.4.3.1 5(-reductase inhibitors
2.4.3.2 (1-Adrenoreceptor antagonists
2.4.3.3 Other drugs
2.4.3.4 Phytotherapy
2.5 Drugs in development
2.6 Epidemiology
2.6.1 Prevalence in the US
2.6.2 Prevalence in Japan
2.6.3 Prevalence in Europe
2.7 Market value


CHAPTER 3 MEN'S CANCERS
3.1 Prostate cancer
3.1.1 Pathology
3.1.2 Risk factors and prevention
3.1.2.1 Diet
3.1.2.2 Vitamin and mineral supplements
3.1.2.3 Genetic implications
3.1.2.4 Vasectomy and risk
3.1.3 Detection and diagnosis
3.1.3.1 Tests
3.1.3.2 Tests in development
3.1.4 Grading
3.1.5 Staging
3.1.6 Treatment
3.1.6.1 Radiotherapy
3.1.6.2 Other treatments
3.1.6.3 Hormonal preparations
3.1.6.4 Hormonal preparations in development
3.1.7 Clinical trials
3.1.7.1 The Prostate Cancer Prevention Trial
3.1.7.2 Adjuvant therapy for non-locally advanced prostate cancer
3.1.7.3 Adjuvant therapy for locally advanced prostate cancer
3.1.7.4 The Early Prostate Cancer Programme
3.1.8 Future therapies
3.1.8.1 Gene therapy
3.1.8.2 Vaccines
3.1.8.3 Other novel therapies in development
3.1.9 Prognosis
3.1.10 Epidemiology
3.1.11 Market value
3.2 Testicular cancer
3.2.1 Risk factors
3.2.2 Types of testicular cancer
3.2.3 Detection and diagnosis
3.2.4 Tumour markers
3.2.5 Staging
3.2.6 Treatment
3.2.6.1 Surgery
3.2.6.2 Radiotherapy
3.2.6.3 Chemotherapy
3.2.6.4 Stem cell transplantation
3.2.7 Management
3.2.7.1 Etoposide
3.2.8 Products in development
3.2.8.1 Testisin
3.2.8.2 MKK4
3.2.8.3 Cisplatin plus Extra technology
3.2.9 Prognosis
3.2.10 Epidemiology
3.2.10.1 EU
3.2.10.2 US
3.2.11 Market value


CHAPTER 4 ERECTILE DYSFUNCTION
4.1 Background
4.1.1 Vascular disorders
4.1.2 Neurological disorders
4.1.3 Endocrine disorders
4.1.4 Diabetes
4.1.5 Drug-related erectile dysfunction
4.2 Risk factors
4.3 Diagnosis
4.4 Treatment
4.4.1 Oral preparations
4.4.1.1 Dose
4.4.1.2 Safety issues
4.4.1.3 Viagra as a lifestyle drug
4.4.1.4 Postmarketing adverse effects of Viagra
4.4.1.5 Who pays?
4.4.2 Intracavernosal injection preparations
4.4.3 Transurethral preparations
4.4.4 Vacuum constriction devices
4.4.5 Penile prosthesis
4.4.6 Testosterone therapy
4.5 Drugs in development
4.5.1 Topical preparations
4.5.1.1 Alprox-TD
4.5.1.2 Topiglan
4.5.1.3 Med 900
4.5.2 Transurethral preparations
4.5.2.1 Alibra
4.5.2.2 Harvard Scientific's liquid formulation of alprostadil
4.5.3 Injection systems
4.5.3.1 Medi-Ject needle-free injection system
4.5.3.2 PowderJect needle-free injection system
4.5.3.3 Invicorp
4.5.4 New oral preparations
4.5.4.1 Vasomax
4.5.4.2 Uprima
4.5.4.3 IC351
4.5.5 Intranasal products
4.5.6 Chinese herbal medicine
4.6 Epidemiology
4.7 Market value


CHAPTER 5 ANDROGEN REPLACEMENT THERAPY
5.1 The importance of testosterone
5.2 Hypogonadism
5.3 Treatment of hypogonadism
5.3.1 Oral preparations
5.3.2 Intramuscular preparations
5.3.3 Testosterone implants
5.3.4 Transdermal preparations
5.3.5 Topical gels
5.3.5.1 Andractim
5.3.5.2 AndroGel
5.4 Patient monitoring in hypogonadism
5.5 Testosterone replacement and the ageing male
5.6 Market value


CHAPTER 6 ALOPECIA
6.1 Background
6.2 Pathology
6.3 Diagnosis
6.4 Treatment
6.4.1 Minoxidil
6.4.2 Finasteride
6.4.2.1 Clinical studies with finasteride
6.4.3 Non-medical procedures
6.4.3.1 Hair transplants
6.4.3.2 Hair implants
6.5 Drugs in development
6.6 Gene therapy
6.7 AGA and coronary heart disease
6.8 Prognosis
6.9 Epidemiology
6.10 Market value


CHAPTER 7 THE REGULATION OF FERTILITY
7.1 Introduction
7.2 Contraception
7.2.1 Hormonal methods
7.2.1.1 Testosterone
7.2.1.2 Androgen-progestogen combinations
7.2.1.3 GnRH analogues
7.2.1.4 Androgen-antiprolactin combinations
7.2.1.5 Androgens in combination with other suppressive agents
7.2.1.6 Novel androgens
7.2.2 Non-hormonal agents
7.2.2.1 Vaccines in development
7.2.2.2 Other developments
7.2.3 Calcium antagonists as potential male contraceptives
7.3 Infertility
7.3.1 Aetiology
7.3.2 Diagnosis
7.3.3 Treatment options
7.3.3.1 Human chorionic gonadotrophin
7.3.3.2 Humegon
7.3.3.3 Gonal-F
7.3.3.4 Intra-Cytoplasmic Sperm Injection
7.3.3.5 Treatment of idiopathic infertility
7.3.4 Products in development
7.3.5 New developments
7.3.5.1 Germ cell transplantation
7.3.5.2 Two-step in vitro fertilisation
7.3.5.3 Sperm capacitation


CHAPTER 8 COMPANY PROFILES
8.1 Abbott Laboratories
8.1.1 Financial highlights
8.1.2 Products marketed for men's healthcare
8.1.3 Products in development for men's healthcare
8.2 Akzo Nobel
8.2.1 Financial highlights
8.2.2 Products marketed for men's healthcare
8.2.3 Research into men's healthcare
8.3 ALZA Corporation
8.3.1 Financial highlights
8.3.2 Products marketed for men's healthcare
8.3.3 Products in development for men's healthcare
8.4 Ares-Serono International SA
8.4.1 Financial highlights
8.4.2 Products marketed for men's healthcare
8.5 AstraZeneca
8.5.1 Financial highlights
8.5.2 Products marketed for men's healthcare
8.5.3 Products in development for men's healthcare
8.6 Calydon Inc
8.7 Immucon
8.7.1 Products in development for men's healthcare
8.8 Merck & Co Inc
8.8.1 Financial highlights
8.8.2 Products marketed for men's healthcare
8.9 Novogen
8.9.1 Financial highlights
8.10 Pfizer Inc
8.10.1 Financial highlights
8.10.2 Products marketed for men's healthcare
8.10.3 Products in development for men's healthcare
8.10.4 Pfizer-Warner-Lambert merger
8.11 Pharmacia Corporation
8.11.1 Financial highlights
8.11.2 Products marketed for men's healthcare
8.11.3 Products in development for men's healthcare
8.12 Takeda Chemical Industries Ltd
8.12.1 Financial highlights
8.12.2 Products marketed for men's healthcare
8.13 TAP Pharmaceuticals
8.13.1 Financial highlights
8.14 Yamanouchi Pharmaceutical Co Ltd
8.14.1 Financial highlights
8.14.2 Products marketed for men's healthcare
8.14.3 Products in development for men's healthcare
8.15 Zonagen Inc
8.15.1 Financial highlights
REFERENCES


LIST OF TABLES
Table 1.1 Deaths in men and women under 75 years in the UK, 1998

Table 2.1 (1-Adrenoreceptor antagonists launched for the treatment of BPH
Table 2.2 Drugs in clinical development for the treatment of BPH
Table 2.3 Drugs in preclinical development for the treatment of BPH
Table 2.4 Population estimates by age range US males (million), 2000-2025
Table 2.5 Estimated number of men who meet the criteria for treatment of BPH in the US by age range (million), 2000-2025
Table 2.6 Estimated number of men who meet the criteria for treatment of BPH in the US, using Bruskewitz's data (million), 2000-2025
Table 2.7 Estimated number of men aged 55+ years suffering from BPH in Japan (million), 2000-2010
Table 2.8 Population estimates of men aged 60 years and over in Europe (million), 2000-2010
Table 2.9 Estimated prevalence of symptomatic BPH in Western Europe in men aged 60 years and over (million), 2000-2010
Table 2.10 Percentage market share of medical therapies for BPH by region, 1998
Table 2.11 Sales and forecast sales of BPH drugs by company ($ million), 1997-2002
Table 2.12 Sales and forecast sales of BPH drugs by company ($ million), 1997-2002
Table 2.13 Sales and forecast sales of Cardura and Hytrin ($ million), 1997-2002

Table 3.1 TNM staging system for prostate cancer
Table 3.2 Stage groupings for prostate cancer
Table 3.3 Drugs launched for the treatment of prostate cancer
Table 3.4 Hormonal therapies in development for the treatment of prostate cancer
Table 3.5 Gene therapy products in development for the treatment of prostate cancer
Table 3.6 Vaccines in development for the treatment of prostate cancer
Table 3.7 Other drugs in development for the treatment of prostate cancer
Table 3.8 Incidence and mortality of prostate cancer by region, 1998
Table 3.9 Age-specific incidence of prostate cancer by region, 1998
Table 3.10 Age-specific prevalence of prostate cancer by regions (thousand), 1998
Table 3.11 Prevalence rates of prostate cancer in the EU at one, three and five years from diagnosis by region (45-75+ years). Estimated and recorded data, 1995
Table 3.12 Survival chances for prostate cancer by region: percentage of patients alive after five years
Table 3.13 Mortality from prostate cancer in the UK, 1950-1997
Table 3.14 Sales and forecast sales of prostate cancer drugs by company ($ million), 1997-2002
Table 3.15 Sales and forecast sales of prostate cancer drugs by company ($ million), 1997-2002
Table 3.16 Staging system for testicular cancer
Table 3.17 Incidence and mortality of testicular cancer in the EU by region (all ages), 1995
Table 3.18 Crude incidence and mortality rates (per 100,000 population) for testicular cancer by region (all ages)
Table 3.19 Prevalence rates of testicular cancer at one, three and five years from diagnosis by region (15-75+ age group). Estimated and recorded data, 1995
Table 3.20 Incidence and mortality of testicular cancer in the US (all ages), 1997-1999

Table 4.1 Advantages and disadvantages of treatment options for erectile dysfunction
Table 4.2 Drugs launched for the treatment of erectile dysfunction
Table 4.3 Drugs in clinical development for the treatment of erectile dysfunction
Table 4.4 Attempts resulting in erection firm enough for intercourse (per patient)
Table 4.5 Number of men aged 40-70 years by region (million), 2000-2010
Table 4.6 Number of men aged 40-70 years estimated to be suffering from erectile dysfunction, by region (million), 2000-2010
Table 4.7 The number of men aged 20 years by region (million), 2000-2010
Table 4.8 Estimated number of men aged 20 years with erectile dysfunction by region (million), 2000-2010
Table 4.9 Estimated1 number of men with erectile dysfunction by region
Table 4.10 Sales and forecast sales of erectile dysfunction drugs by company ($ million), 1997-2002
Table 4.11 Sales of drugs to treat erectile dysfunction by company, 1997-2002 ($ million)

Table 5.1 Effects of androgens and consequences of androgen deficiency in men
Table 5.2 Products launched and in development for male hypogonadism
Table 5.3 Criteria for monitoring testosterone substitution therapy
Table 5.4 Number of men estimated to be suffering from hypogonadism by region (million), 2000-2010
Table 5.5 Sales and forecast sales of testosterone patches in the US ($ million), 1997-2002

Table 6.1 Drugs in development for the treatment of alopecia
Table 6.2 Other compounds in development for alopacia
Table 6.3 Sales and forecast sales of Merck & Co's Propecia ($ million), 1998-2002
Table 6.4 Male population, by region, and estimated number with AGA, according to age (million), 2000-2010
Table 6.5 Total number of men estimated to have AGA by region (million), 2000-2010
Table 6.6 Men aged 30-60 years estimated to have AGA who could be eligible for treatment by region (million), 2000-2010

Table 7.1 Products in development for the treatment of male infertility

Table 8.1 Abbott's financial highlights ($ million), 1996-1999
Table 8.2 Akzo Nobel's financial highlights ($ million), 1996-1999
Table 8.3 Akzo Nobel's sales distribution by region, 1999
Table 8.4 ALZA's financial highlights ($ million), 1996-1999
Table 8.5 Ares-Serono's financial highlights ($ million), 1996-1999
Table 8.6 Ares-Serono sales by area ($ million), 1998 and 1999
Table 8.7 Astra Zeneca's financial highlights ($ million), 1998-1999
Table 8.8 AstraZeneca's sales distribution by region ($ million), 1998-1999
Table 8.9 Sales of AstraZeneca's Zoladex and Casodex ($ million), 1998-1999
Table 8.10 Merck & Co's financial highlights ($ million), 1996-1999
Table 8.11 Pfizer's financial highlights ($ million), 1996-1999
Table 8.12 Pfizer's sales distribution by region ($ million), 1998
Table 8.13 Pharmacia & Upjohn's financial highlights ($ million), 1996-1999
Table 8.14 Pharmacia & Upjohn's sales distribution by region ($ million), 1997-1999
Table 8.15 Takeda's financial highlights ($ million), 1996-1999
Table 8.16 TAP Pharmaceutical's net sales, 1995-1998
Table 8.17 Yamanouchi's financial highlights ($ million), 1996-1999
Table 8.18 Yamanouchi's sales distribution by region, 1999
Table 8.19 Yamanouchi's pharmaceutical sales by category, 1999
Table 8.20 Zonagen's financial highlights ($ thousand), 1996-1999
Table 8.21 Zonagen's products in clinical trials


LIST OF FIGURES
Figure 1.1 Population data for men aged over 50 years by region, 2000-2025

Figure 2.1 Estimated number of suffers of BPH in Japan, 1991-1998

Figure 3.1 Sites of anticancer drug action in the prostate cell
Figure 3.2 The incidence of prostate cancer in the US, 1994-1999
Figure 3.3 The age-related incidence of prostate cancer in the EU
Figure 3.4 The incidence of testicular cancer in the EU (per 100,000 population)
Figure 3.5 The age-related incidence of testicular cancer in the EU (per 100,000 population)
Figure 3.6 Sales and forecast sales of etoposide, 1997-2002

Figure 4.1 Cross section of the penis
Figure 4.2 The biochemical mechanism of erection

Figure 6.1 Cycle of scalp hair growth
Figure 6.2 Miniaturisation of hair follicle growth during the balding process and its reversal by therapy

Figure 7.1 A schematic representation of the endocrine mechanism controlling testicular function
Figure 7.2a The principle of hormone contraception using testosterone
Figure 7.2b The principle of hormone contraception using testosterone plus GnRH antagonists


EXECUTIVE SUMMARY
Men die on average five years earlier than women, partly because they have less healthy lifestyles which leads to a higher incidence of disease but also because they risk a late diagnosis and treatment by not going to a doctor immediately problems arise. Although the gap between men and women of higher socioeconomic class is now narrowing, this is not the case for those of less affluent backgrounds. However, the situation is beginning to change and men's health is now receiving greater public and medical recognition. Dedicated healthcare professionals are finding new strategies for encouraging men to take more responsibility for their own health and in the UK and elsewhere, governments are beginning to take note of the problem too.

The market for drugs to treat men's health problems has been growing steadily since the mid-1980s and is expected to do so well into the next decade. Growth is due in part to the increased public and medical awareness of men's health issues. However, it is also due to demographic shifts which mean that more men are now over 50 years of age and the numbers of older men will continue to grow in the future. The pharmaceutical industry has recognised the potential of the men's health market and is developing many new products which are described in the report.

A very common disorder in elderly men is benign prostatic hyperplasia (BPH), an androgen-dependent enlargement of the prostate gland which affects as many as 50% of men over the age of 60. It is responsible for a complex of lower urinary tract symptoms which include increased frequency of urination, nocturia (night time urination), difficulty in urinating, urgency, leakage and pain in the lower back, pelvis or upper thighs. If the condition is mild, it is managed by 'watchful waiting' but more serious cases require surgical or medical intervention. Pharmacological intervention is preferred for moderate cases and offers two classes of drugs, 5(-reductase inhibitors (eg finasteride) and (-adrenoreceptor antagonists (eg doxazozin, tamsulosin). The former inhibit the synthesis of the biologically active androgen, dihydrotestosterone, and bring about tumour regression while the latter relax smooth muscle and improve urine flow by blocking (-adrenoreceptors in the prostate gland and the bladder neck. (-Adrenoreceptor antagonists are the preferred medical treatment because they are fast acting, well tolerated and unlike finasteride, do not affect sexual function.

It is important that men seek treatment for BPH early on because the symptoms are similar to those of prostate cancer, especially in the early stages. Prostate cancer has a serious mortality rate and is second only to lung cancer regarding cancer-related death in men. All too often it is not diagnosed until it has reached an advanced stage by which time the prognosis is poor. It is a disease of older men with only 15% of cases occurring in patients under the age of 65. Treatment for localised disease includes surgery or radiotherapy. For advanced disease (over 40% of cases) hormonal therapy is indicated. The options include, androgen withdrawal (with luteinising hormone-releasing hormone (LHRH) agonists eg goserelin or leuprorelin), androgen blockade (with an antiandrogen, eg bicalutamide, in combination with an LHRH agonist) or inhibition of androgen synthesis (with a 5(-reductase inhibitor eg finasteride). New LHRH analogues are in development, as are new formulations of existing drugs. Gene therapies, vaccines and numerous other agents are under investigation.

Testicular cancer, unlike prostate cancer it is one of the rarest forms of cancer (1% of all male cancers) but it is the most common malignancy in the 15-34 year age group. Testicular neoplasms are particularly sensitive to chemotherapy and are highly curable if treated at an early stage but men are dying unnecessarily because they fail to self-check or leave it too late to seek advice. Treatment involves surgery, radiotherapy, chemotherapy (for more advanced disease) and stem cell transplantation.

A milestone in the growth of the men's health sector was the launch of the erectile dysfunction drug Viagra (sildenafil). The intense demand for the drug suggests that the incidence of erectile dysfunction has been grossly underestimated. The perception of Viagra as a 'lifestyle' drug has fuelled debate about how it should be prescribed and who should pay but whatever the outcome, a vast market has been uncovered with more than 100 million men worldwide estimated to be suffering from the condition. The most common cause of erectile dysfunction is vascular disease but it is also due to co-existing conditions such as diabetes, hypogonadism and neurological disorders. Until the launch of Viagra, treatment involved intracavernosal injection of alprostadil (Caverject), transurethral therapy with alprostadil (MUSE), vacuum constriction devices and penile prostheses. In development are topical preparations, two-drug combination transurethral therapy, more patient-friendly injection systems, an oral formulation of the (-adrenoreceptor antagonist, phentolamine mesylate (Vasomax) and a sublingual preparation of apomorphine (Uprima).

Androgen replacement therapy is currently used for the treatment of hypogonadism, which is an irreversible condition characterised by impaired testosterone production in which the characteristics of male maturity do not develop. It is treated with testosterone replacement therapy but the challenge has been to find a way to replace testosterone in suitably physiological concentrations. Current research is focused on developing the transdermal route although intramuscular injections are still used by the majority of patients. ALZA's trans-scrotal patch, Testoderm and SmithKline Beecham's non-scrotal patch, Andropatch, are the two currently available products. Future alternatives could be topical gels and more biopotent androgens. Testosterone levels decline as part of the ageing process and there is increasing interest in using the technology as hormone replacement therapy for elderly men. The advantages of replacement therapy for this indication would be increased lean body mass, increased libido, osteoporosis prevention and an imbued feeling of well being for the patient.
Male-pattern hair loss (androgenetic alopecia) is another androgen-related condition that is linked with ageing; 50% of men over the age of 50 are affected to some extent and many men would welcome the opportunity of reversing the condition. Although (with the exception of a hair transplant) this is not an option, improved understanding of the balding process has led to the development of two drugs which can help, namely, finasteride (Propecia, 1mg, Merck & Co) and minoxidil (Rogaine, Pharmacia & Upjohn). These drugs have enjoyed considerable success in terms of sales and analysts predict that this trend will continue.

Researchers have been in pursuit of a male hormonal contraceptive for some years now but at last a realistic option is in sight. The most promising candidate is an androgen-progestogen combination which is administered as a transdermal testosterone patch and a progestogen pill. Vaccines offer an alternative approach to the challenge.

Male factor infertility (the cause of the problem in about 40% of infertile couples) is a growing concern fuelled by evidence of a 50% decline in sperm count over the last 50 years. Some disturbances of fertility can be explained and treated but for around 40% of infertile men there is no explanation and no treatment. Possible causes and current and potential treatments are discussed.
The report profiles a cross section of companies marketing and/or developing products for men's health. It includes information on the background and financial highlights of the companies and lists products marketed and in development.

© PJB Publications Ltd. 2000
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