不安障害治療薬のパイプライン分析

Abstract

Overview

Introduction

The global anxiety disorders market is set to decline from $4.5 billion in 2006 to $2.6 billion by 2015 (CAGR 2006-15 -6.0%). This will be primarily due to the launch of numerous generic anxiety drugs from 2006 onwards, which will offset the revenue growth derived from existing drugs seeking additional anxiety indications, and the launch of several novel anxiety drugs.

Scope

• Detailed pipeline analysis for key products in development for GAD, SAD, OCD, PTSD, PMDD and panic disorder, plus drug sales forecasts to 2015
• Overview of patient potential segmentation by indication and unmet needs in anxiety disorders across the US, Japan, France, Germany, Italy, Spain & UK
• Benchmarking of key clinical and company attractiveness of late-phase pipeline products
• Detailed clinical trial information and opinions from key thought leaders

Report Highlights

To maximize drug revenues as a final step before generic incursion, a number of existing market players are seeking approvals in additional anxiety indications. However, sales of $1.6 billion in 2006 will decline over the long-term to $1.2 billion in 2015.

Manufacturers with existing branded CNS drugs already approved for indications other than anxiety, are also seeking secondary indications in the anxiety market. Datamonitor forecasts that these drugs will enter the anxiety market from 2007 onwards, and will reach peak anxiety specific revenues of $413m in 2013.

Several novel anxiety drugs will be launched over the forecast period from 2006 onwards, including Predix's PRX-00023 (oral non-azapirone 5-HT1A agonist) in Phase III for GAD, and Schering AG/Berlex's YAZ (low dose drospirenone/ethinyl estradiol) and Wyeth's Librel (low dose levonorgestrel/ethinyl estradiol), both in development for PMDD.

Reasons to Purchase

• Understand unmet needs in the anxiety market based on key opinion leader comments regarding both currently marketed and pipeline products
• Benchmark key late-stage anxiety compounds against current market leaders
• Assess the global sales forecasts of late-stage pipeline drugs for anxiety and examine their clinical and commercial potential

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

• About the CNS pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

• Scope of the analysis
• Datamonitor insight into the anxiety market
• Key metrics

CHAPTER 2 PATIENT POTENTIAL

• Etiology of anxiety disorders
  • Generalized anxiety disorder
  • Panic disorder
  • Social anxiety disorder
  • Obsessive-compulsive disorder
  • Post-traumatic stress disorder
  • Premenstrual dysphoric disorder
  • Agoraphobia
  • Specific phobias
• Classification of anxiety disorders
  • ICD-10 classification
  • DSM-IV classification
  • Diagnosis algorithm
• Epidemiology of anxiety
  • Prevalence of anxiety disorder types
    • Generalized anxiety disorder
    • Panic disorder
    • Social anxiety disorder
    • Obsessive-compulsive disorder
    • Post-traumatic stress disorder
    • Premenstrual dysphoric disorder
    • Agoraphobia
    • Specific phobias
    • Other anxiety disorders
• Key patient segments
  • Acute versus chronic anxiety
  • Gender and age
  • Comorbidities of anxiety disorders
• Unmet needs in anxiety disorders
  • Improving patient compliance is key
    • Improving the perceived therapeutic efficacy throughpatient education
    • Patient education and public awareness
    • Faster onset of action on the horizon
    • Limiting side effects is essential
    • Targeting comorbidity expands the prescribing potential ofa drug

CHAPTER 3 R&D APPROACH

• Classification of marketed and pipeline products
  • Serotonergics
  • Noradrenergics
  • GABAergic drugs
  • Novel therapies
• Clinical trials and drug development
  • Clinical trial endpoints and anxiety rating scales
    • Hamilton Anxiety (HAM-A)
    • Hospital Anxiety and Depression scale (HADS)
    • Liebowitz Social Anxiety Scale (LSAS)
    • Patient Global Impression of Improvement Scale (PGI)
    • Clinical Global Impression Improvement Scale (CGI-I)
    • Social Phobia and Anxiety Inventory (SPAI)
    • Social Phobia Inventory (SPIN)
    • Clinician Administered PTSD Scale (CAPS)
    • Treatment Outcome PTSD Scale
    • Davidson Trauma Scale (DTS)
    • Short PTSD Rating Interview (SPRINT)
    • Brief Social Phobia Scale fear subscale
    • Panic Disorder Severity Scale (PDSS)
    • Panic and Agoraphobia Scale (PAS)
    • Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
    • The National Institute of Mental Health ObsessiveCompulsive Scale (NIMH-OC)
    • Daily Record of Severity of Problems (DRSP)
    • Other scales
  • Clinical trial design guidance
    • Inclusion criteria
    • Exclusion criteria
    • Assessing efficacy
    • Strategy and design of clinical trials
  • Key research recommendations

CHAPTER 4 MARKETED AND PIPELINE ANXIETY DRUG OVERVIEW

• Marketed anxiety drug overview
  • The market value is calculated using IMS diagnosis value
  • Forecast caveats
• Pipeline overview
  • Anxiety drugs in Phase III and above
  • Anxiety drugs in Phase II
  • Anxiety drugs in Phase I
  • Key companies involved in the anxiety pipeline
    • GSK
    • Wyeth
    • Lilly
  • Other key companies involved in the anxiety pipeline
    • Sanofi-Aventis
    • Fabre Kramer
• Methodology of SWOT analysis
  • Gold standard anxiolytic
    • Generalized Anxiety Disorder
    • Obsessive Compulsive Disorder
    • Panic Disorder
    • Social Anxiety Disorder
    • Premenstrual Dysphoric Disorder
    • Post traumatic stress disorder

CHAPTER 5 GAD PIPELINE DRUG OVERVIEW

• Overview of GAD drugs
• Launched drugs
• Pipeline summary
  • Lyrica (pregabalin)
    • Clinical trial data
  • Cymbalta (duloxetine)
    • Clinical trial data
    • Recently completed clinical trials
    • Ongoing clinical trials
  • PRX-00023
    • Clinical trial data
    • Ongoing clinical trials
  • SR-58611
    • Ongoing clinical trials
  • Gabitril (tiagabine)
    • Clinical trial data
    • Ongoing clinical trials
  • Seroquel SR (quetiapine sustained release)
    • Clinical trial data
  • AC-5216
    • Ongoing clinical trials
  • MN-305 (osemozotan / MKC-242)
  • Jazz Pharma
    • Ongoing clinical trials
  • Recently discontinued pipeline drugs

CHAPTER 6 OCD PIPELINE DRUG OVERVIEW

• Overview of OCD drugs
• Launched drugs
• Pipeline summary
  • Lexapro (escitalopram)
    • Clinical trial data
    • Ongoing clinical trials
  • Luvox CR (fluvoxamine controlled release)
    • Clinical trial data

CHAPTER 7 SAD PIPELINE DRUG OVERVIEW

• Overview of SAD drugs
• Launched drugs
• Pipeline summary
  • Luvox CR (fluvoxamine controlled release)
    • Clinical trial data
  • Lexapro (escitalopram)
    • Clinical trial data
  • Cymbalta (duloxetine)
    • Ongoing clinical trials
  • TGWOOAD/AA
  • LY686017
    • Ongoing clinical trials
  • Gabitril (tiagabine)
    • Clinical trial data
    • Completed clinical trials
  • casopitant (GW679769)
    • Ongoing clinical trials

CHAPTER 8 PD PIPELINE DRUG OVERVIEW

• Overview of PD drugs
• Launched drugs
• Pipeline summary
  • Lexapro (escitalopram)
    • Clinical trial data
  • TGAR01P

CHAPTER 9 PTSD PIPELINE DRUG OVERVIEW

• Overview of PTSD drugs
• Launched drugs
• Pipeline summary
  • Risperdal (risperidone)
    • Clinical trial data
    • Ongoing clinical trials
  • Paxil CR (paroxetine controlled release)
    • Ongoing clinical trials
  • Gabitril (tiagabine)
    • Clinical trial data
  • Effexor XR (venlafaxine extended release)
    • Clinical trial data

CHAPTER 10 PMDD PIPELINE DRUG OVERVIEW

• Overview of PMDD drugs
• Launched drugs
• Pipeline summary
  • YAZ (drospirenone and ethinyl estradiol)
    • Clinical trial data
  • Librel (levonorgestrel / ethinyl estradiol)
    • Ongoing clinical trials

CHAPTER 11 NON-SPECIFIED ANXIETY DISORDERS DRUG OVERVIEW

• Non-specified anxiety disorders drug overview
• Launched drugs
• Pipeline summary
  • alprazolam
  • AP-521
  • ELB139
    • Clinical trial data
  • vestipitant (GW597599) + paroxetine
  • Recently suspended pipeline drugs

CHAPTER 12 ANALYSIS AND FORECASTS OF PIPELINE ANXIETYDRUGS

• Analysis and forecasts of pipeline anxiety drugs
  • Lyrica (pregabalin)
    • Lyrica demonstrates a strong safety and efficacy profile,with a fast onset
    • Schedule V may limit patient uptake in the US
    • Lyica will become a first-line treatment for pure GAD
    • Lyricas anxiety revenues will slow the decline ofPfizers anxiety franchise
    • Threat from generic gabapentin?
    • Lyrica will be the next new anxiety drug to reach themarket
  • Cymbalta (duloxetine)
    • Cymbaltas side effects will limit uptake in anxiety
    • Lack of clear differentiation from venlafaxine in anxiety
    • Global partnerships enhance commercial prospects ofCymbalta
    • Cymbaltas revenue growth in the anxiety market will beshort lived
  • PRX-00023
    • Physicians are unconvinced with the therapeutic potentialof PRX-00023
    • PRX-00023 will be used to augment SSRI therapy
    • PRX-00023 is unlikely to compete on the same therapeuticplain as the SSRIs
  • SR-58611
    • Efficacy in severe depression may carry over into anxiety
    • Initial off-label usage will support growth in GAD onceapproved
  • Gabitril (tiagabine)
    • Physicians unimpressed by Gabitrils efficacy in anxiety
    • FDA seizure warning severely threatens Gabitrils patientpotential
    • Treatment of comorbid pain in GAD
    • Gabitrils commercial potential is limited
    • Gabitril is unlikey to receive FDA approval for GAD
  • Seroquel SR (quetiapine sustained release)
    • A strong safety and efficacy profile in schizophrenia andBD bodes well for use in anxiety
    • Seroquel will retain patent protection until 2011,protecting the initial uptake of Seroquel SR
    • Targeting community based psychiatric disorders will favorSeroquel SRs growth
  • AC-5216
    • Physicians are skeptical of the therapeutic potential ofAC-5216
  • MN-305 (Osemozotan / MKC-242)
    • The record for the 5-HT1A partial agonists has beenappallingly bad
    • MediciNova will need to find a marketing partner
  • Jazz Pharma
  • Lexapro (escitalopram)
    • US non-approvals for SAD and PD will limit future revenues
    • Lack of pipeline compounds will limit long-term anxietyrevenues for Lundbeck and Forest
    • Lexapro will retain patent protection until 2011
    • Lexapros anxiety specific revenues will continue to growthrough 2009
  • Luvox CR (fluvoxamine controlled release)
    • Luvox will continue to grow in Japan, despitegenericization
    • Luvox CR is commercial suicide
  • TGWOOAD/AA
    • TGWOOAD/AAs mode of action is not particularly unique
    • Fabre Kramer will need to find a marketing partner
  • TGAR01P
    • Physicians have serious concerns regarding TGAR01P
    • Datamonitor does not expect that TGAR01P will receive FDAapproval
  • LY686017
  • Risperdal (risperidone)
    • Risperdal demonstrates efficacy in reducing the symptomsof PTSD
    • J&J has limited time to gain FDA approval forRisperdal for PTSD before the availability of generic risperidone
  • Paxil CR (paroxetine controlled release)
    • GSK faces several hurdles in terms of establishing PaxilCR as a first-line treatment for PTSD
  • GSKs NK1 antagonists - casopitant (GW679769) andvestipitant (GW597599)
    • Combination of an NK1 antagonist and SSRI shows potential
  • Effexor XR (venlafaxine extended release)
    • Effexor XRs recent approval for PD will certainly boostrevenues
    • US and EU patent expiries lead to erosion of Effexor XRrevenues from 2008 onwards
  • YAZ (drospirenone and ethinyl estradiol)
    • YAZ will provide an alternative treatment to women whofeel that there is a stigma attached to taking an SSRI
    • No PMDD market in the EU limits revenue potential
    • YAZ is expected to continue to grow Schering AG/Berlexsflagship womens health franchise
  • Librel (levonorgestrel / ethinyl estradiol)
    • Librels continuous regimen may provide a competitiveadvantage
    • Librels uptake will be limited by YAZs first to marketstatus
  • NovaDels alprazolam oral spray
    • Improved therapeutic potential remains uncertain despite ahead-to-head trial with alprazolam tablets
    • NovaDel will have difficulty in gaining FDA approval forthe formulation
    • Datamonitor does not expect oral spray alprazolam willreceive FDA approval
  • AP-521
  • ELB139

CHAPTER 13 INNOVATIVE EARLY-STAGE PROJECTS

• Overview of innovative early-stage projects
  • NK receptor antagonists
  • ALXZ-002
  • Synthetic human secretin
    • The subcutaneous formulation is unlikely be received wellby patients
  • CRF antagonists
  • 5-HT agonists
  • Metabotropic glutamate receptor 5 modulators
  • MAO inhibitors
  • CCK antagonists
  • PDE 2 inhibitor
  • Vasopressin
  • Future treatment of anxiety disorder

APPENDIX A

• Forecast revenues
• Anxiety market data
• Competitive positioning analysis of pipeline anxiety drugs
• Bibliography
  • Journal articles and conference abstracts

APPENDIX B

• Report methodology
  • Datamonitor forecast methodology
    • Sales calculations
• About Datamonitor
  • About Datamonitor Healthcare
• Datamonitor Healthcares therapy area capabilities

List of Tables

• Table 1: Forecast revenues ($m) of marketed and pipelineanxiety drugs across the seven major markets, 2006-15
• Table 2: ICD-10 classification codes for anxietydisorders
• Table 3: DSM-IV classification codes for anxietydisorders
• Table 4: Prevalence rate of sub-categories of anxietydisorder in the general population across the seven major markets
• Table 5: Prevalence of GAD
• Table 6: Prevalence of panic disorder
• Table 7: Prevalence of SAD in four of the major markets
• Table 8: Prevalence of OCD
• Table 9: Prevalence of a comorbid psychiatric conditionwith anxiety disorders across the seven major markets
• Table 10: Marketed anxiety drugs approved for specificanxiety disorders, in the US, EU and Japan.
• Table 11: Percentage of total molecule volume (accountedfor by anxiety, diagnosis value, 2005 (MAT Q4 2004 to Q3 2005)
• Table 12: Drugs seeking approval for anxietyindications, 2006
• Table 13: Drugs in Phase III development for anxietydisorders, 2006
• Table 14: Drugs in Phase II development for anxietydisorders, 2006
• Table 15: Drugs in Phase I development for anxietydisorders, 2006
• Table 16: GSKs global CNS franchise, 2005
• Table 17: GSKs marketed and pipeline anxiety drugs,2006
• Table 18: Wyeths global CNS portfolio, 2004-05
• Table 19: Wyeths marketed and pipeline anxiety drugs,2006
• Table 20: Lillys global CNS portfolio, 2005
• Table 21: GSKs marketed and pipeline anxiety drugs,2005
• Table 22: Commercial strength / weakness factors -weightings and scoring definitions
• Table 23: Product specific strength / weakness factors -weightings and scoring definitions
• Table 24: Drugs approved for GAD
• Table 25: Drugs in Phase II development or above for GAD
• Table 26: Pipeline drugs recently discontinued fromdevelopment for GAD
• Table 27: Drugs approved for OCD
• Table 28: Drugs in Phase II development or above for OCD
• Table 29: Drugs approved for SAD
• Table 30: Drugs in Phase II development or above for SAD
• Table 31: Drugs approved for PD
• Table 32: Drugs in Phase II development or above for PD
• Table 33: Drugs approved for PTSD
• Table 34: Drugs in Phase II development or above forPTSD
• Table 35: Drugs approved for PMDD
• Table 36: Drugs in Phase II development or above forPMDD
• Table 37: Drugs approved for non-specified anxietydisorders
• Table 38: Drugs in late-stage development fornon-specified anxiety disorders
• Table 39: Pipeline drugs recently suspended fromdevelopment for non-specified anxiety disorders
• Table 40: Proportion (%) of drug revenues attributed toanxiety disorders for Gabitril and approved anxiety drugs
• Table 41: Estimated patient and revenue potential of YAZin PMDD
• Table 42: Estimated patient and revenue potential ofLibrel in PMDD
• Table 43: Drugs in Phase I clinical development foranxiety disorders, 2006
• Table 44: Forecast revenues ($m) of marketed andpipeline anxiety drugs across the seven major markets, 2006-15
• Table 45: Prozac key facts
• Table 46: Key Prozac events, 2005-2006
• Table 47: Prozac key facts
• Table 48: Paxil key facts
• Table 49: Key Paxil events, 2005-2006
• Table 50: Zoloft: key facts
• Table 51: Key Zoloft events, 2005-2006
• Table 52: Celexa: key facts
• Table 53: Lexapro: key facts
• Table 54: Key Lexapro/Cipralex events, 2005-2006
• Table 55: Luvox: key facts
• Table 56: Key Luvox events, 2005-2006
• Table 57: Effexor: key facts
• Table 58: Key Effexor events, 2005-2006
• Table 59: Xanax: key facts
• Table 60: Buspar: key facts
• Table 61: Cymbalta: key facts
• Table 62: Key Cymbalta events, 2005-2006
• Table 63: Lyrica: key facts
• Table 64: Key Lyrica events, 2005-2006
• Table 65: Gabitril: key facts
• Table 66: Key Gabitril events, 2005-2006
• Table 67: Datamonitors competitive positioning analysisof pipeline anxiety drugs compared to existing market players (1 of 2)
• Table 68: Datamonitors competitive positioning analysisof pipeline anxiety drugs compared to existing market players (2 of 2)
• Table 69: Anxiety disorders market definition by ICD10code

List of Figures

• Figure 1: Datamonitors forecast for anxiety specificrevenues of pipeline and marketed anxiety drugs across the seven majormarkets, 2006-15
• Figure 2: Datamonitors SWOT analysis of pipeline drugs.
• Figure 3: Anxiety disorders diagnostic decision tree(DSM-IV)
• Figure 4: Patient distribution: acute versus chronicanxiety
• Figure 5: Reasons why patients receiving antidepressanttherapy are non-compliant
• Figure 6: Drug classes in development for the treatmentof anxiety disorders.
• Figure 7: NICE measurement of cost-effectiveness of drugtreatment
• Figure 8: Revenues of the Paxil franchise after genericincursion
• Figure 9: US Drugstore Paxil prescriptions for anxietydisorders, 2003-05
• Figure 10: US revenue split of Paxil and Paxil CRbetween anxiety disorders and alternative indications, 2002-05
• Figure 11: Forecast revenues of the Paxil franchiseacross the seven major markets, 2006-15
• Figure 12: US revenue split of the Effexor franchise XRbetween anxiety disorders and alternative indications, 2002-05
• Figure 13: Forecast revenues of the Wyeths anxietyfranchise across the seven major markets, 2006-15
• Figure 14: US revenue split of Prozac between anxietydisorders and alternative indications, 2002-05
• Figure 15: Forecast revenues of Lillys anxietyfranchise across the seven major markets, 2006-15
• Figure 16: Physician rated performance of main drugsused in the treatment of anxiety disorders
• Figure 17: Datamonitors SWOT analysis of GAD pipelinedrugs
• Figure 18: Datamonitors SWOT analysis of OCD pipelinedrugs
• Figure 19: Datamonitors SWOT analysis of SAD pipelinedrugs
• Figure 20: Datamonitors SWOT analysis of PD pipelinedrugs
• Figure 21: Datamonitors SWOT analysis of PTSD pipelinedrugs
• Figure 22: Datamonitors SWOT analysis of PMDD pipelinedrugs
• Figure 23: The pharmacologic profile of Lyrica comparedto paroxetine
• Figure 24: Forecast revenues of Pfizers anxietyfranchise across the seven major markets, 2006-15
• Figure 25: Anxiety specific revenue forecast for Lyricaacross the seven major markets, 2006-15
• Figure 26: The pharmacologic profile of Cymbaltacompared to paroxetine
• Figure 27: Anxiety specific revenue forecast forCymbalta across the seven major markets, 2006-15
• Figure 28: The pharmacologic profile of PRX-00023compared to paroxetine
• Figure 29: Anxiety specific revenue forecast forPRX-00023 across the seven major markets, 2006-15
• Figure 30: The pharmacologic profile of SR5-8611compared to paroxetine
• Figure 31: Quarterly revenues of Gabitril (2004-05)
• Figure 32: The pharmacologic profile of Gabitrilcompared to paroxetine
• Figure 33: US revenue split of Gabitril between anxietydisorders and alternative indications, 2002-05
• Figure 34: The pharmacologic profile of Seroquel SRcompared to paroxetine
• Figure 35: US revenue split of Lexapro between anxietydisorders and alternative indications, 2002-05
• Figure 36: The pharmacologic profile of Lexapro comparedto paroxetine
• Figure 37: US cash market share of Forest/Lundbecksantidepressant franchise from 2002-05
• Figure 38: Anxiety specific revenue forecast for Lexaproacross the seven major markets, 2006-15
• Figure 39: The pharmacologic profile of Luvox CRcompared to paroxetine
• Figure 40: The pharmacologic profile of TGWOOAD/AAcompared to paroxetine
• Figure 41: The pharmacologic profile of Risperdalcompared to paroxetine
• Figure 42: The pharmacologic profile of Paxil CRcompared to paroxetine
• Figure 43: Anxiety specific revenue forecast for PaxilCR across the seven major markets, 2006-15
• Figure 44: The pharmacologic profile of Effexor XRcompared to paroxetine
• Figure 45: Anxiety specific revenue forecast for EffexorXR across the seven major markets, 2006-15
• Figure 46: The pharmacologic profile of YAZ compared toparoxetine
• Figure 47: Anxiety specific revenue forecast for YAZacross the seven major markets, 2006-15
• Figure 48: The pharmacologic profile of Librel comparedto paroxetine
• Figure 49: Anxiety specific revenue forecast for Librelacross the seven major markets, 2006-15