Pipeline Insight: Depression

Summary

Introduction

Datamonitor believes that companies developing pipeline drugs for the depression market should concentrate resources on targeting third-line depression patients, a market with significant sales volume and few viable treatment options. GSK's gepirone ER is likely to be the first pipeline drug to enter the market and exploit this opportunity, with forecast sales of $615m in 2016.

Scope

• Analysis of patient potential, unmet needs and clinical trial design in depression
• Overview of drugs in late- and early-stage clinical development; with analysis of key companies involved in the market
• Detailed profiles of key compounds in development for use in depression, with forecasts of drug revenues to 2016
• Discussion of GSK's and Sanofi-Aventis' strategies, and insight from key industry opinion leaders

Highlights

Of the novel pipeline drugs in late-stage development for depression, Datamonitor believes gepirone ER has the most revenue potential over the forecast period. This will be the first pipeline drug to enter the market and compete for market share with current third-line therapies, and has the considerable marketing support of GSK.

Wyeth's lifecycle management strategy of developing the Effexor reformulation Pristiq, will not successfully maintain revenues for its depression franchise following generic incursion of Effexor XR in 2010.

Agomelatine, a melatonin agonist and serotonin receptor ligand, will be a valuable treatment option for mild/moderate MDD patients with prominent sleep disorder co-morbidity or an add-on therapy for more severe MDD sufferers.

Reasons to Purchase

• Understand unmet needs in the depression market based on key opinion leader comments
• Benchmark key late-stage depression compounds against current market leaders
• Assess the global (US, Japan, five major EU) sales forecasts of key late-stage pipeline drugs; and examine their clinical and commercial potential

Contents

• 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)