Market Report Source

Overview

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

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

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