Pain Therapeutics 2005: Market Dynamics and Outlook

1        Methodology and Executive Summary
1.1          Report Objectives and Scope
1.2          Research Methodology
1.3          Executive Summary

2        Causes, Classifications and Global Impact of Pain
2.1          Causes
2.1.1        Terminal Illness
2.1.2        Pain and Genetics
2.1.3        The Immune System and Pain
2.1.4        The Subjective Nature of Pain
2.1.5        Pain Transmission
2.1.5.1     Nociceptors
2.1.5.2     Pain Receptors
2.2           Classifications
2.2.1        Chronic Pain
2.2.2        Acute Pain
2.3           The Impact of Pain
2.3.1        Demographic Impact
2.3.2        Financial Cost of Pain

3        Treating Pain: Drug Classes and Guidelines
3.1           NSAIDs
3.2           Opioids
3.2.1        Chronic Pain and Opioids
3.3           Antidepressants
3.4           Anticonvulsants

4        Post-Operative Pain Overview and Therapeutic Options
4.1           Impact of Post-Operative Pain
4.2           Pain Intensity in Surgical Sites
4.3           Site-specific Pain Relief
4.4           Postoperative Medications
4.4.1        Naropin
4.4.2        DepoDur, DepoMorphine and Propofol
4.4.3        Other Opioids for Pain Management
4.4.4        NSAIDs for Postoperative Pain

5        Back Pain Overview and Therapeutic Options
5.1           Sciatica
5.2           Facet Joint Problems
5.3           Osteoarthritis
5.4           Diseases and Back Pain
5.5           Low Back Pain
5.6           Pharmaceutical Relief for Back Pain
5.6.1        Transdermal Patches
5.6.2        Injections for Back Pain
5.6.3        Back Pain and Opioids
5.6.4        Tricyclic Antidepressants
5.6.5        Muscle Relaxers
5.6.6        Colchicine
5.6.7        Chronic Low Back Pain and Anticonvulsants

6        Neuropathic Pain Overview and Therapeutic Options
6.1           Nociceptive Versus Neuropathic Pain
6.2           Nociceptive and Neuropathic Mixed Pain
6.3           Neuropathic Pain
6.4           Neuropathic Pain Generation
6.5           Treating Neuropathic Pain
6.5.1        Transdermal Fentanyl
6.5.2        Ketamine and Alfentanil
6.5.3        Neurontin
6.5.4        Lyrica

7        Migraine Overview and Therapeutic Options
7.1           Impact of Migraines
7.2           Pharmacological Treatment of Migraine Pain
7.2.1        Fiorinal and Fioricet
7.2.2        Ergot Alkaloid Derivatives
7.2.3        Triptans
7.2.3.1     Comparing Triptans
7.2.3.2     Imitrex
7.2.3.3     Zomig
7.2.3.4     Maxalt
7.2.3.5     Relpax
7.2.4        Neuroleptics
7.2.5        Beta-blockers
7.3           New and Investigational Drugs for Migraine Pain
7.3.1        Topamax
7.3.2        Alexza
7.3.3        Botox
7.3.4        Trexima
7.4           Alternative Therapies for Migraine

8        Cancer Pain Overview and Therapeutic Options
8.1           Causes of Cancer Pain
8.2           Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and Cancer Pain
8.3           Opioids and Cancer Pain
8.3.1        Reluctance to Prescribe Opioids
8.4           Seizure Drugs for Cancer Pain
8.5           Investigational Drugs
8.5.1        Remoxy
8.5.2        Ziconatide
8.5.3        Chronogesic Pain Therapy System
8.5.4        Xen2174

9        Arthritic Pain Overview and Therapeutic Options
9.1           Impact of Arthritis
9.2           Rheumatoid Arthritis
9.2.1        Causes
9.2.2        RA Demographics
9.2.3        Genetic Susceptibility
9.2.4        Environmental Factors
9.2.5        High Cost of Rheumatoid Arthritis
9.3           Osteoarthritis
9.3.1        Causes
9.3.2        Pharmacological Treatment of Osteoarthritis
9.3.2.1     COX-2 Class
9.3.3        Pharmacological Treatment of Rheumatoid Arthritis
9.4           Antirheumatic Drug Classes
9.4.1        Nonsteroidal Anti-Inflammatory Drugs
9.4.2        Corticosteroids
9.4.3        Disease Modifying Anti-Rheumatic Drugs (DMARDs)
9.4.4        DMARD Competition
9.4.5        Slow-Acting Antirheumatic Drugs (SAARDs)
9.4.6        Biological Response Modifiers (BRMs)
9.4.7        Leading RA Medications
9.4.8        BRMs Versus DMARDs

10        Fibromyalgia Overview and Therapeutic Options
10.1         Manifestations
10.2         Impact of Fibromyalgia
10.3         Natural Treatments for Fibromyalgia
10.4         Prescription Treatments for Fibromyalgia
10.4.1      Treatment with Antidepressants
10.4.2      Muscle Relaxants
10.4.3      Sleep Modifiers
10.4.4      Anxiety Medications
10.4.5      Anticonvulsants
10.4.6      Antibiotics
10.5         Future Therapies for Fibromyalgia

11        Non-Pharmaceutical Pain Treatment
11.1        Acupuncture
11.1.1     Assessing Acupuncture’s Value
11.2        Osteopathic Manipulation
11.2.1     Osteopathic Treatment
11.2.2     Conditions Treated by Osteopaths  
11.3        Physiotherapy
11.4        Reflexology
11.5        Neurostructural Integration Technique
11.6        Herbal medicine
11.7        Neurolytic Block Injections
11.7.1     Examples of Neurolytic Blocks
11.8        Chemical Neurolytic Blocks
11.9        Cryoablation
11.10      Radiofrequency Lesioning
11.11      Neurosurgical Procedures
11.12      Chemical Ablation
11.13      Nerve Blocks
11.14      Neurostimulation and Pain Control
11.15      Electro Thermal Disc Decompression/ Intradiscal Electro Thermocoagulation
11.16      Selective Nerve Root Injections
11.17      Facet Joint Pain Block
11.18      Trigger Spot Injections
11.19      Peripheral Nerve Injections
11.20      Cervical and Lumbar Epidural Blocks

12        NSAID Market Analysis
12.1         Overview
12.2         Over-the-Counter NSAIDs
12.2.1      Ibuprofen
12.2.2      Naproxen
12.2.3      Acetaminophen and Aspirin
12.3         Traditional Prescription NSAIDs
12.3.1      Diclofenac/Cataflam/Voltaren
12.3.2      Arthrotec
12.3.3      Mobic
12.3.3.1   Mobic’s Market Share
12.3.3.2   Mobic Vs Other NSAIDs
12.3.4      DayPro
12.3.4.1   Rheumatoid Arthritis Relief from DayPro
12.3.4.2   Osteoarthritis Relief from DayPro
12.3.5      Relafen
12.3.5.1   Relafen Versus Naproxen and Aspirin
12.3.5.2   Endoscopy Trials
12.4         The Future of the NSAID Market

13        Opioid Use and Market Trends
13.1           Drawbacks of Opioid Therapy
13.2           Treating Chronic Pain
13.3           Key Opioid Products
13.3.1        Morphine
13.3.1.1     Increased Usage of Morphine
13.3.1.2     Cognitive and Psychomotor Effects
13.3.1.3     Extended Release Morphine
13.3.2        Oxycodone
13.3.3        Kadian
13.3.3.1     Key Clinical Trial
13.3.4        Vicodin
13.3.5        Ultracet/Ultram
13.3.6        Duragesic
13.4           Legal Regulation of Opioids
13.5           Side Effects
13.6           Adjuvant Medications
13.7           Market Analysis
13.7.1        OxyContin
13.7.2        Duragesic
13.7.3        Kadian
13.7.4        Ultracet/Ultram
13.7.5        Avinza
13.7.6        Actiq
13.8           Key Opioid Products in Development
13.8.1        Chronogesic
13.8.2        Ionsys
13.8.3        Remoxy
13.9           The Future of the Opioid Market

14        Migraine Therapy Market
14.1           Overview
14.2           Leading Migraine Therapies
14.2.1        Imitrex/Imigran
14.2.2        Zomig
14.2.3        Relpax
14.2.4        Maxalt
14.3           Preventive vs. Abortive Therapy
14.4           The Future of the Migraine Market

15        Anticonvulsant Market
15.1           Overview
15.2           Leading Anticonvulsants
15.2.1        Neurontin
15.2.1.1     Generic Competition
15.2.2        Topamax
15.2.3        Depakote
15.2.4        Lamictal
15.2.5        Trileptal
15.2.6        Tegretol
15.3           The Future of the Anticonvulsant Market

16        Cox-II Inhibitors and the Future
16.1           The Fall of Bextra
16.1.1        Health Risks Alert
16.1.2        Thromboembolic Events
16.1.3        Post-marketing Reports for Bextra
16.1.4        Withdrawal of Bextra
16.2           The Fall of Vioxx
16.2.1        Public Health Advisory
16.2.2        Repercussions from the Vioxx Withdrawal
16.2.3        Fear of COX-2 Inhibitors
16.2.4        Financial Fallout for Merck
16.2.5        Vioxx vs Other Cox-2 Inhibitors
16.3           Celebrex: Surviving the Fallout
16.3.1        FDA Review of Clinical Trials
16.3.2        Black Box Warning
16.4           Future Scrutiny of Cox-2 Class
16.5           COX-2 Pipeline
16.5.1        Prexige
16.5.1.1     TARGET Assessment
16.5.2        Arcoxia
16.5.2.1     Future of Arcoxia
16.5.3        Dynastat
16.6           The Future of the Cox-II Class

17        Promising Areas of Research
17.1           Natural Painkillers
17.1.1        Peptides
17.1.2        Epibatidine
17.1.3        Chili Peppers and Capsaicin
17.1.4        Marijuana
17.1.5        Receptors as Gateways
17.1.6        Chromaffin Cells
17.1.7        Glutamate
17.1.8        Prialt
17.1.9        New Class of Analgesics

18        Company Briefs
Abbott Laboratories
AlgoRx Pharmaceuticals
Altea Therapeutics
Ardent Pharmaceuticals
AstraZeneca
Cephalon
Elan Pharmaceuticals
Endo Pharmacuticals
EpiCept
GlaxoSmithKline
Indevus Pharmaceuticals
Innovative Drug Delivery Systems
Johnson & Johnson
Metaphore Pharmaceuticals
Nastech Pharmaceutical
NeurogesX
Novartis Pharmaceuticals
Pain Therapeutics
Pfizer
Purdue
Renovis
SkyePharma


Tables and Graphs
Table 1.1          Value of the Pain Market, by Therapeutic Class 2004
Graph 1.1         Value of the Pain Market, by Therapeutic Class Market Share 2004
Table 1.2          Top Ten Pain Medications Worldwide in 2004
Graph 1.2         Fastest Growing Pain Medication Classes, by Growth Rate
Table 1.3          Key Patent Expirations for Pain Therapies
Table 2.1          Characteristics and Treatment of Acute vs Chronic Pain
Graph 2.1         Top Causes of Pain
Table 2.2          Incidence of pain conditions in American households
Table 3.1          Key Pain Management Drug Classes and Diseases/Conditions Treated
Table 3.2          NSAID Delivery Routes
Table3.3           Traditional NSAIDs
Table 3.4          The Oxford League Table of Analgesic Efficacy
Table 3.5          Well Known Narcotic Analgesics
Table 3.6          WHO Guidelines for Pain Therapy
Table 4.1          WFSA Analgesic Ladder
Table 6.1          Department of Health and Human Services Assistive Tool for Determining Type of Pain
Table 7.1          Estimated annual costs of migraine for the total population of patients with migraine
Table 7.2          Popular Medicines for the Treatment of Migraines
Table 7.3          Preventive Headache Therapies
Table 7.4          Common Analgesics Prescribed for Migraine Pain
Table 7.5          Ergot Alkaloid Derivatives for Migraine Pain Spray
Table 7.6          NSAIDs and COX-2 Inhibitors
Table 7.7          Triptans for Migraine Pain
Table 7.8          Patent Expirations for Leading Triptans
Table 7.9          Migraine Drugs In Development
Table 8.1          Cancer Pain and Therapeutic Options
Table 8.2          Adjuvants to Opioids for Treating Cancer Pain
Table 9.1          Leading Causes of Disabilities in the US
Table 9.2          Approved DMARDs for Rheumatoid Arthritis
Table 9.3          Profiles of the Leading DMARDs
Table 9.4          Sales of Biologics for Rheumatoid Arthritis, 1999-2004
Graph 9.1         Growth of Biologics for Rheumatoid Arthritis 2000-2004
Table 10.1        Popular Treatments for Fibromyalgia
Table 11.1        Complementary and Alternative Medicine Use by U.S. Adults--2002
Table 11.2        10 Most Common Complementary and Alternative Therapies 2002
Table 11.3        Disease/Condition for Which Complementary/Alternative Medicines are Most 
Frequently Used
Table 12.1        Global Sales of Leading Prescription NSAIDs (Traditional) 2004
Graph 12.1        Prescription NSAID Product Market Share (traditional vs Cox-2 Inhibitors) 2004
Graph 12.2        Prescription NSAID Product Market Share 2004
Table 12.2         Sales of Advil 2002-2004
Table 12.3         Sales of Aleve 2002-2004
Table 12.4         Sales of Excedrin 2002-2004
Table 12.5         Rejuvenation of Mobic Sales 2003-2004
Table 12.6         Adverse Events (%) Occurring in 2% of MOBIC Patients in a 12-Week Osteoarthritis 
Placebo and Active-Controlled Trial
Table 12.7         Traditional NSAIDs and Past Sales (Pre-Cox 2) 1998-1999
Table 13.1         Key Opioid Product Sales 2004
Graph 13.1        Global Market Share of Branded Opioid Products 2004
Table 13.2         Sales Growth in the US Opioids Market 1997-2002
Graph 13.2        Sales Growth in the US Opioids Market 1997-2004
Table 13.3         Consumer cost of analgesics and adjuvants (2000) Medication Size Cost
Table 13.4         Sales of OxyContin 2003-2004
Table 13.5         Sales of Duragesic 2001-2004
Graph 13.3        The Success of Duragesic: Global Sales 2001-2004
Table 13.6         Sales of Kadian 2002-2004
Table 13.7         Sales of Ultracet/Ultram 2001-2003
Table 13.8         Sales of Avinza 2003-2004
Table 13.9         Sales of Actiq 2002-2004
Table 13.10        Financial Forecast of the Global Opioid Market 2004-2009
Table 14.1         Sales of Triptan Drugs 2001-2004
Graph 14.1        Sales of Triptan Drugs 2001-2004
Table 14.2         Sales of Leading Migraine Therapies 2004
Graph 14.2        Leading Migraine Therapies, Market Share 2004
Graph 14.3        Geographic Market Share of Leading Triptan-Based Migraine Therapies 2004
Table 14.3         Global Sales of Imitrex/Imigran 2001-2004
Table 14.4         Global Sales of Zomig 2001-2004
Table 14.5         Global Sales of Relpax 2001-2004
Table 14.6         Global Sales of Maxalt 2001-2004
Table 14.7         Financial Forecast of Triptans 2005-2009
Table 15.1         Leading Anticonvulsants, Global Sales 2004
Graph 15.1        Leading Anticonvulsants, Market Share 2004
Table 15.2         Sales Growth in the Anticonvulsants Market 2001-2004
Graph 15.2        Sales Growth in the Anticonvulsants Market 2001-2004
Table 15.3         Leading Anticonvulsant Indications
Table 15.3         Global Sales of Neurontin 2001-2004
Table 15.4         Global Sales of Topamax 2001-2004
Table 15.5         Global Sales of Depakote 2001-2004
Table 15.6         Global Sales of Lamictal 2001-2004
Table 15.7         Global Sales of Trileptal 2001-2004
Table 15.8         Global Sales of Tegretol 2001-2004
Table 15.9         Financial Forecast of the Anticonvulsant Market 2004-2009
Table 16.1         Leading COX-2 Inhibitors 2004
Table 16.2         Post-Bextra Switching Trends
Table 16.3         Future Sales of Celebrex
Table 18.1         The Value of Pfizer’s Pain Management Portfolio 2004 ($ mn)
Table 18.2         Purdue Pharma’s Prescription Pain Portfolio
Table I              Global Sales of Leading Pain Management Drugs 2004
Table II             Pain Management Pipeline
Table III           Acute Pain Pipeline
Table IV            Chronic Pain Pipeline
Table V             Neuropathic Pain Pipeline
Table VI            Post-operative Pain Pipeline
Table VII           Severe Pain Pipeline
Table  IX           NSAIDs Affected by Newly Required Warning Labels

Appendices
Table I             Global Sales of Leading Pain Management Drugs 2004
Table II            Pain Management Pipeline
Table III           Acute Pain Pipeline
Table IV           Chronic Pain Pipeline
Table V            Neuropathic Pain Pipeline
Table VI           Post-operative Pain Pipeline
Table VII          Severe Pain Pipeline
Table  IX          NSAIDs Affected by Newly Required Warning Labels