[Report] Pipeline Insight: Depression - Novel drugs to grow third-line market TOC

CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the depression market
  - Summary
- Key metrics
- Datamonitor Pipeline Assessment Summary
CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS
- Pipeline overview
  - Pipeline drugs in pre-registration and registration
  - Pipeline drugs in Phase III clinical development
  - Pipeline drugs in Phase II clinical development
  - Discontinued and suspended projects
    - CP-316311 and CP-122721
    - Aprepitant and L-759274
    - Dilopetine
    - MN-305
    - OPC-14523
    - Radafaxine
- Key companies involved in the depression pipeline
  - GSK
    - Paxil
    - Wellbutrin
    - GSK will hope that pipeline drugs fill the gap left by Paxil' s decline
  - Sanofi-Aventis
- Key R&D company strategies
  - Reformulation strategies
    - Drug delivery reformulations
    - Chemical reformulation
  - Secondary indications
- Datamonitor' s gold standard MDD drug
  - Paxil chosen due to its frequent incorporation into clinical trial designs
CHAPTER 3 DEPRESSION - MARKET POTENTIAL
- Definition of depression
  - DSM-IV
  - ICD-10
- Segmentation of MDD
  - Elderly MDD
  - Child and adolescent MDD
- Epidemiology of depression
  - MDD prevalence in the major markets
    - 12-month prevalence rate of 6.6% in the US
    - 12-month prevalence rate of 6.7% across Europe
    - Substantially lower prevalence rate in Japan than in the US or Europe
    - Age group variance in MDD prevalence rate
  - Diagnosis and treatment
  - Current classes used in depression treatment
    - MAOIs and TCAs-effective but side effects and safety are a concern
    - SSRIs retain the efficacy of MAOIs and TCAs but with more favorable side-effect and safety profiles
    - SNRIs have added to the treatment options, but are generally not used first-line
    - Treatment algorithms for MDD
  - Co-morbid disorders
    - More than half of MDD sufferers also suffer from anxiety
- Unmet needs in depression
  - Faster onset of action
  - Side effects
  - Patient compliance
  - Efficacy
    - Efficacy may be low for first monotherapy, but improves at second-line
    - Efficacy similar between currently available antidepressants
  - Better combinations
CHAPTER 4 R&D APPROACH
- Classification of pipeline products
  - Datamonitor' s classification of pipeline products
    - SNRIs
    - Triple reuptake inhibitors
    - NK receptor antagonists
    - Serotonin receptor ligands
    - Other therapies
- Clinical trial design in depression
  - Patient population
  - Placebo effect
- Clinical trial endpoints in depression
  - Hamilton Rating Scale for Depression
  - Hamilton Rating Scale for Anxiety
  - Montgomery-Asberg Depression Rating Scale
  - Clinical Global Impression Scale
  - The Beck Depression Rating Scale
  - The Zung Self-Rating Depression Scale
  - Brief Psychiatric Rating Scale
CHAPTER 5 SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview for SNRIs
  - Pipeline summary
  - Definition of current comparator therapy
    - Effexor XR (venlafaxine extended release)
- Desvenlafaxine (Pristiq)
  - Profile
    - Drug overview: metabolite of the blockbuster Effexor
  - Clinical trial data
    - Efficacy and safety of Pristiq in the treatment of MDD
    - Randomized, double-blind, placebo-controlled study of desvenlafaxine succinate in MDD
    - Adverse events in the two desvenlafaxine Phase III studies
    - Double-blind, placebo- and moxifloxacin-controlled crossover study of the effects of desvenlafaxine succinate on QT interval in healthy adult female subjects
  - Ongoing clinical trials investigating the efficacy of desvenlafaxine as a treatment of MDD
  - Preclinical
  - Patient potential
  - Marketing factors
  - Satisfaction of unmet needs
  - Forecasts to 2016
    - Generic Effexor XR launch
    - Switching from Effexor XR to Pristiq in the estimated two years before the launch of generics
  - Datamonitor drug assessment summary
CHAPTER 6 TRIPLE REUPTAKE INHIBITORS (SEROTONIN/NOREPINEPHRINE/DOPAMINE) LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview for triple reuptake inhibitors
  - Pipeline summary
  - Triple reuptake inhibitors are designed to inhibit the reuptake of serotonin, norepinephrine and dopamine
    - Studies investigating triple reuptake inhibition with two separate compounds
  - Definition of current comparator therapy
    - Effexor XR
- DOV-216 303
  - Profile
    - Drug overview : DOV-216,303 has a complicated licensing history
  - Clinical trial data
    - Phase II clinical trial
    - Phase 1b clinical trial
    - Phase 1a clinical trial
  - Preclinical studies
  - Datamonitor comments
- NS-2359 (GSK372475)
  - Profile
    - Drug overview: triple reuptake inhibitor under development by GSK
  - Ongoing clinical trials
  - Datamonitor comments
CHAPTER 7 NK RECEPTOR ANTAGONISTS LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview for NK receptor antagonists
  - Pipeline summary
  - Lack of efficacy of the NK1 receptor antagonist aprepitant in the treatment of MDD
  - Definition of current comparator therapy
- Saredutant
  - Profile
    - Drug overview: NK2 receptor antagonist
  - Clinical trials data
    - Phase IIb clinical trial data
  - Preclinical data
  - Ongoing clinical trial program for saredutant in MDD
  - Patient potential
    - Room for an alternative mode of action in the depression market
    - Possible indication expansion into anxiety and pain
  - Marketing factors
    - Sanofi-Aventis has a broad experience of marketing drugs to psychiatrists
  - Satisfaction of unmet needs
    - Speed of onset of action
    - Side effects
    - Patient compliance
    - Better combinations
  - Forecasts to 2016
    - Saredutant could gain market share from current third-line therapies
  - Datamonitor drug assessment summary
- Other NK receptor modulators in development
  - Casopitant
  - Vestipitant + paroxetine
CHAPTER 8 SEROTONIN RECEPTOR LIGANDS LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview for serotonin receptor ligands
  - Pipeline summary
  - Definition of current comparator therapy
- Gepirone ER
  - Profile
    - Drug overview: resubmission likely six years following original submission
    - Regulatory submissions
  - Clinical trial data
    - Relapse prevention with gepirone ER in outpatients with MDD
    - Retrospective subgroup analysis in patients with MDD
    - Sustained efficacy of gepirone-IR in MDD: a double-blind placebo substitution trial
    - Relapse prevention with gepirone ER in outpatients with MDD
    - Effect of gepirone ER on sexual function in patients with MDD
    - Gepirone ER in patients with anxious depression
    - Effects of gepirone ER on depression with anxiety symptoms: a double-blind, placebo-controlled study
    - Gepirone ER: new evidence for efficacy in the treatment of MDD
    - Phase II relapse prevention during long-term gepirone IR therapy for MDD: a double-blind substitution trial
  - Patient potential
  - Marketing factors
  - Satisfaction of unmet needs
    - Faster onset of action
    - Side effects
    - Patient compliance
    - Efficacy
    - Better combinations
  - Forecasts to 2016
  - Gepirone ER will gain market share from third-line therapies in the US and EU
  - Datamonitor drug assessment summary
- Quetiapine (Seroquel SR)
  - Profile
    - Drug overview: atypical antipsychotic
  - Clinical trial data
    - BOLDER I-A randomized, double-blind, placebo-controlled trial of Seroquel (quetiapine) in the treatment of bipolar I or II depression.
    - BOLDER II-Efficacy of Seroquel (quetiapine) monotherapy in bipolar depression: A confirmatory double-blind, placebo-controlled study
  - Ongoing clinical trial program for Seroquel SR in MDD
  - Current state of development
- Vilazodone
  - Profile
    - Drug overview: targeting niche sub-population of MDD sufferers
    - Genetically guided antidepressant
  - Clinical trial data
    - Phase III program
  - Preclinical
  - Ongoing clinical trial program
  - Current state of development
- Other Serotonin receptor ligands
  - Elzasonan
  - F-2695
CHAPTER 9 OTHER THERAPIES LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview for other therapies
  - Pipeline summary
  - Definition of current comparator therapy
- Agomelatine
  - Profile
    - Drug overview: the first melatonergic antidepressant
    - Failed European submission by Servier
    - US filing by Novartis
  - Clinical trial data
    - Placebo-controlled trial of agomelatine in the treatment of MDD presented at the 13th Congress of the Association of European Psychiatrists (April 2005).
    - Placebo-controlled trial of agomelatine in the treatment of MDD
    - Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with Paxil: a randomized, double-blind, placebo-controlled discontinuation study.
    - Double-blind pilot study comparing the therapeutic effect of two doses of agomelatine in the treatment of MDD
    - Determination of the dose of agomelatine, a melatonergic agonist and selective 5-HT2C antagonist, in the treatment of MDD: a placebo-controlled dose range study.
    - Melatonin and agomelatine increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis.
  - Ongoing clinical trials
  - Patient potential
  - Marketing factors
  - Satisfaction of unmet needs
    - Faster onset of action
    - Side effects
    - Patient compliance
    - Efficacy
    - Better combinations
  - Forecasts to 2016
    - Significant market share gained from hypnotics currently prescribed for depression
  - Datamonitor drug assessment summary
- Nemifitide
  - Profile
  - Clinical trial data
    - Double-blind, placebo-controlled study of nemifitide in the treatment of outpatients with MDD
    - Phase IIc open-label extension study
    - Phase IIa - A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of nemifitide, a novel antidepressant peptide, in the treatment of major depression
    - Clinical pharmacokinetic studies with INN 00835 (nemifitide), a novel pentapeptide antidepressant
  - Preclinical
  - Patient potential
  - Marketing factors
  - Satisfaction of unmet needs
    - Faster onset of action
    - Side effects
    - Patients compliance
    - Efficacy
    - Better combinations
  - Forecasts to 2016
    - Uptake is slow and market share gain limited due to route of administration
  - Datamonitor drug assessment summary
- Corlux (mifepristone)
  - Profile
    - Drug overview: specifically targeting psychotic depression
  - Clinical trial data
    - Corcept 09
    - Corcept 07
    - Corcept 03 - Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression
    - Corcept 02 - Clinical and biological effects of mifepristone treatment for psychotic depression
    - An eight-week open-label trial of a six-day course of mifepristone for the treatment of psychotic depression
    - An open-label trial of C-1073 (mifepristone) for psychotic major depression
    - Rapid reversal of psychotic depression using mifepristone
  - Ongoing clinical trial program for mifepristone in MDD
- Amibegron
  - Profile
    - Drug overview: beta-3 adrenergic receptor agonist
  - Clinical trial data
    - Phase III European study in patients with a recurrent major depressive episode (EFC 5374)
    - EFC 5379 - Non-conclusive result from North American study
  - Ongoing clinical trial program for amibegron in MDD
- Other novel therapies in clinical development
  - Miraxion (LAX-101)
  - BMS-562086
  - TRIDMAC
    - Clinical trial data
  - Org 24448
  - Org 34517
    - Ongoing clinical trials
  - SSR149415
    - Ongoing clinical trials
  - YKP10A
    - Phase II study
    - Phase I
CHAPTER 10 INNOVATIVE EARLY-STAGE PROJECTS
- Key Phase I and preclinical compounds in MDD
- Key Phase I compounds in depression
  - TC-2216
    - How are NNRs and depression linked?
    - Preclinical and clinical development of TC-2216
  - SEP-225289
BIBLIOGRAPHY
- Journals
- Websites
APPENDIX A
- Methodology
  - Datamonitor forecast methodology
    - ICD-10 codes used to define current depression market
    - Estimated 2006 sales revenue
    - MDD specific sales calculations
    - Product forecasts
    - Definition of a standard unit
    - Japanese market data
  - Datamonitor drug assessment summary
- Report methodology
APPENDIX B
- About Datamonitor
  - About Datamonitor Healthcare
- Datamonitor Healthcare' s therapy area capabilities
  - Disclaimer
- List of Tables
  - Table 1: Datamonitor' s forecast MDD revenues of key pipeline drugs and the total MDD market across the seven major markets ($m), 2008-2016
  - Table 2: Key pipeline drugs in registration and pre-registration for MDD in the seven major markets, 2007
  - Table 3: Key pipeline drugs in Phase III development for MDD in the seven major markets, 2007
  - Table 4: Key pipeline drugs in Phase II development for MDD, 2007
  - Table 5: Prevalence rate and population size for MDD across the seven major markets, 2007
  - Figure 6: Non-cost related unmet needs in MDD, 2007
  - Table 6: Key SNRI class drugs in the late-stage MDD R&D pipeline, 2007
  - Table 7: Estimated key events, approvals and launch dates impacting Pristiq' s revenue forecast, 2006-2016
  - Table 8: Key triple reuptake inhibitor class drugs in the late-stage MDD R&D pipeline, 2007
  - Table 9: Key NK receptor antagonist class drugs in the late-stage MDD R&D pipeline, 2007
  - Table 10: Estimated key events, approvals and launch dates impacting saredutant' s revenue forecast, 2006-2016
  - Table 11: Key serotonin receptor ligands class drugs in the late-stage MDD R&D pipeline, 2007
  - Table 12: Estimated key events, approvals and launch dates impacting gepirone ER' s revenue forecast, 2006-2016
  - Table 13: Key other therapies class drugs in the late-stage MDD R&D pipeline, 2007
  - Table 14: Estimated key events, approvals and launch dates impacting agomelatine' s revenue forecast, 2006-2016
  - Table 15: Estimated key events, approvals and launch dates impacting nemifitide' s revenue forecast, 2006-2016
  - Table 16: Key pipeline drugs in Phase I development for MDD, 2007
  - Table 17: Key pipeline drugs in preclinical development for MDD, 2007
  - Table 18: Possible roles of neuronal nicotinic receptors
  - Table 19: ICD-10 and DSM-IV codes for MDD
- List of Figures
  - Figure 1: Datamonitor' s MDD drug assessment summary
  - Figure 2: Drugs in development at each stage of development for MDD, 2007
  - Figure 3: $1.8 billion decrease in GSK' s global depression portfolio between 2003 and 2006.
  - Figure 4: Company reported, all-indication global sales revenue for Prozac, 2000-05
  - Figure 5: STAR*D treatment algorithm for depression
  - Figure 7: Effexor (venlafaxine) versus SSRIs
  - Figure 8: Datamonitor' s forecast of MDD specific sales for Pristiq across the seven major markets ($m), 2006-2016
  - Figure 9: Datamonitor' s competitive positioning analysis for Pristiq in MDD
  - Figure 10: Datamonitor' s forecast of MDD specific sales for saredutant across the seven major markets ($m), 2006-2016
  - Figure 11: Datamonitor' s competitive positioning analysis for saredutant in MDD
  - Figure 12: Datamonitor' s forecast of MDD specific sales for gepirone ER across the seven major markets ($m), 2006-2016
  - Figure 13: Datamonitor' s competitive positioning analysis for gepirone in MDD
  - Figure 14: Dose adjustment of Seroquel for different indications.
  - Figure 15: Datamonitor' s forecast of MDD specific sales for agomelatine across the seven major markets ($m), 2006-2016
  - Figure 16: Datamonitor' s competitive positioning analysis for agomelatine in MDD
  - Figure 17: Datamonitor' s forecast of MDD specific sales for nemifitide across the seven major markets ($m), 2006-2016
  - Figure 18: Datamonitor' s competitive positioning analysis for nemifitide in MDD
  - Figure 19: Clinical trial path for amibegron MDD trial (EFC5374)

Pipeline Insight: Depression - Novel drugs to grow third-line market

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