てんかん治療薬のパイプライン分析

Abstract

Overview

Introduction

Slow generic uptake, reformulations, follow-on products and new market entrants will ensure steady long-term growth of the epilepsy market despite several high profile patent expiries. UCB has emerged as the number one epilepsy company, and is set to strengthen their epilepsy pipeline if the proposed acquisition of Schwarz is confirmed.

Scope

• Analysis of patient potential, unmet needs and clinical trial design in epilepsy
• Overview of drugs in pre-registration, Phase III, II and I; with analysis of key companies involved in the market
• Detailed profiles of key compounds in development for use in epilepsy, with forecasts of drug revenues to 2015
• Discussion of UCB, Eisai, and GSK' s strategies and insight from key industry opinion leaders

Highlights

Following on from Keppra' s commercial success, UCB is the current epilepsy market leader. UCB' s existing relationship with neurologists will bode well for the potent follow-on compounds, brivaracetam and seletracetam.

UCB' s proposed acquisition of Schwarz will further boost its epilepsy pipeline and CNS marketing/sales capabilities. If the acquisition is completed, Datamonitor believes that UCB will continue to develop Schwarz' s Phase III pipeline product lacosamide.

Generic incursion in the epilepsy market is less profound than in other CNS sectors. Nevertheless, lifecycle management strategies will be necessary to maintain market share following patent expiries. For example, development of sustained release/extended release formulations such as GSK' s Lamictal XR can slow generic incursion.

Reasons to Purchase

• Understand unmet needs in the epilepsy market based on key opinion leader comments
• Benchmark key late-stage epilepsy 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 epilepsy market
    • Summary
• CHAPTER 2 PATIENT POTENTIAL
  • Definition of epilepsy
    • Etiology of epilepsy
    • Diagnosis of epilepsy
  • Epidemiology of epilepsy
  • Segmentation of epilepsy
    • Seizures are categorized according to their location of origin
      • Little difference in prevalence of partial and generalized epilepsy
      • Incidence of epilepsy peaks in early and late life
  • Unmet need in epilepsy
    • Unmet need 1: Efficacious treatments for refractory epilepsy
    • Unmet need 2: Reduction in adverse side effects
    • Unmet need 3: Greater treatment options for elderly patients
    • Unmet need 4: Greater treatment options for pediatric epilepsy
    • Unmet need 5: Compliance
    • Unmet need 6: Non-teratogenic treatments for use in pregnancy
    • Unmet need 7: AEDs which do not react with oral contraception
• CHAPTER 3 R&D APPROACH
  • Classification of pipeline products
    • GABA modulators
    • Ion channel modulators
    • Glutamate modulators
    • Others
  • Clinical trial design in epilepsy
    • ' Add-on' studies are the mainstay in clinical trial design
    • Clinical trial endpoints in epilepsy
    • Post-marketing studies are important for detecting rare adverse events
    • Key difficulties in epilepsy clinical trials
      • Heterogeneity of disease
      • Wide use of patients' self-reporting
      • Applicability of trial results to the elderly population
    • Clinical trial design guidance from the EMEA
  • Current gold standard and comparator therapies
    • Gold standard epilepsy therapy unclear
    • Gold standard for partial epilepsy
    • Gold standard for generalized seizures
      • UCB' s Keppra is the comparator drug for new entrants
      • Numerous indication expansions in the last year
      • Comparison of responder rates for key pipeline, the comparator drug (Keppra) and other marketed AEDs in refractory partial epilepsy
• CHAPTER 4 EPILEPSY PIPELINE ANALYSIS
  • Pipeline overview
    • Drugs in preregistration
    • Pipeline drugs in Phase III
    • Pipeline drugs in Phase II
    • Investigated epilepsy types for each key pipeline drug
  • Key companies involved in the epilepsy pipeline
    • UCB
      • Development of a drug with a novel mode of action and specific focus on epilepsy was a winning strategy for UCB
      • Keppra contributes over half of the revenue gained by UCB' s CNS franchise
      • UCB' s AED portfolio
      • Will UCB follow the same strategies in the future?
    • Eisai
      • Eisai' s CNS strategy is one of inlicensing AEDs
      • Overview of Eisai' s CNS franchise
      • Eisai' s AED portfolio
  • Strategies for success
    • Reformulations
      • Drug delivery methods
      • Chemical reformulations
    • Indication expansion
      • Drug versatility in the treatment of epilepsy
      • Targeting additional therapeutic indications
      • Bipolar disorder treatment is a lucrative market for anticonvulsants
      • Regulatory approval or off-label prescribing?
• CHAPTER 5 GABAERGIC MODULATORS: LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Overview of GABAergic drugs
    • Pipeline summary
  • DP-VPA
    • Profile
      • Drug overview: currently in Phase II for severe forms of epilepsy
    • Clinical data
      • Clinical trial 1: Phase II trials of DP-VPA.
      • Clinical trial 2: Phase I clinical trial data were presented at the Fourth and Fifth Eilat conferences
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
      • Primary benefit would be in an improved side-effect profile
    • Forecasts to 2015
    • Datamonitor drug assessment summary
• CHAPTER 6 ION CHANNEL MODULATORS: LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Overview of Ion channel modulator drugs
    • Pipeline summary
  • Rufinamide
    • Profile
      • Drug overview: currently in preregistration for LGS and adjunctive therapy for partial onset seizures
    • Clinical data
      • Clinical trial 1: The effect of the new antiepileptic drug rufinamide on cognitive functions
      • Clinical trial 2: Efficacy and safety of rufinamide adjunctive therapy in patients with Lennox-Gastaut syndrome.
      • Clinical trial 3: Rufinamide: a double-blind placebo-controlled proof of principle trial in patients with epilepsy
      • Clinical trial 4: Efficacy and safety of rufinamide as adjunctive therapy in adult patients with therapy-resistant partial-onset seizures
      • Preliminary data presented at the 8th Eilat Conference on New Antiepileptic Drugs
    • Patient potential
      • Potential in partial seizures is limited
      • Add-on rather than switching from other therapies
      • High potential for share of the Lennox-Gastaut Syndrome market
    • Marketing factors
      • Expansion outside the domestic market
      • Launch in an under-developed Japanese market
      • Increasing focus of epilepsy treatment
      • Launch of specialized CNS sales force
      • Off-label use following license in Lennox-Gastaut syndrome
    • Satisfaction of unmet needs
      • Additional treatment option for pediatric patients
    • Forecasts to 2015
    • Datamonitor drug assessment summary
  • Retigabine
    • Profile
      • Drug overview: potassium channel opener currently in Phase III development
    • Clinical data
      • Clinical trial 1: Phase II studies of retigabine in epilepsy.
      • Clinical trial 2: Multiple-dose, linear, dose-proportional pharmacokinetics or retigabine in healthy volunteers.
      • Phase II safety studies
      • Additional pharmacokinetic Phase I trials investigating drug interactions with retigabine
    • Ongoing clinical trials
    • Patient potential
    • Marketing factors
      • Valeant has some CNS sales and marketing experience, but a co-marketing deal will be required to realize retigabines revenue generating potential
    • Satisfaction of unmet needs
      • Adverse side-effects may be a concern
      • Similar efficacy for refractory patients as current drugs
      • Patient compliance may be an issue with a three-times a day treatment
      • No reported interactions with oral contraception
    • Forecasts to 2015
    • Datamonitor drug assessment summary
  • Lamictal XR
    • Profile
      • Drug overview: extended release formulation of currently available treatment
    • Clinical trial data
    • Ongoing clinical trials
      • NCT00113165: Study evaluating Lamictal extended-release therapy added to current seizure treatments in patients with partial seizures.
      • NCT00104416: Study evaluating Lamictal extended-release therapy added to current seizure treatments in patients with Primary Generalized Tonic-Clonic (PGTC) seizures
      • NCT00355082: Conversion to monotherapy with Lamictal extended-release tablets for treatment of partial epilepsy
    • Patient potential
    • Marketing factors
      • GSK has had varying success with this type of lifecycle management strategy in the past
      • Following initial high uptake, Paxil CR did not significantly help GSK maintain market share with Paxil
      • Successive launches of Wellbutrin reformulations has helped maintain market share following an initial slump
      • Will Lamical follow the Paxil or Wellbutrin model?
    • Satisfaction of unmet needs
      • Theoretically the side-effect profile may be improved over Lamictal IR
      • Patient compliance may not be increased due to once-a-day dosing regime
    • Forecasts to 2015
    • Datamonitor drug assessment summary
  • Late-stage products recently discontinued
• CHAPTER 7 GLUTAMATE MODULATORS: LATE-STAGE ANALYSIS AND FORECASTS
  • Overview of glutamate modulator drugs
    • Pipeline summary
  • E-2007
    • Profile
      • Drug overview: AMPA glutamate receptor antagonist
  • NS-1209
    • Profile
      • Drug overview: AMPA glutamate receptor and metabotropic glutamate receptor antagonist
  • Ampanel (talampanel)
    • Profile
      • Drug overview: non-competitive AMPA receptor antagonist
    • Clinical data
      • Clinical trial 1: Clinical trial data presented at the seventh Eilat Conference on New Antiepileptic Drugs in Sardinia, Italy (May 2004).
      • Clinical trial 2: A crossover, add-on trial of talampanel in patients with refractory partial seizures.
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
      • No significant efficacy for complex partial seizures
      • Weak side-effect profile in Phase II study
    • Forecasts to 2015
    • Datamonitor drug assessment summary
  • Late-stage products recently discontinued
• CHAPTER 8 OTHER LATE-STAGE PRODUCTS IN CLINICAL DEVELOPMENT
  • Overview of the other AEDs in late-stage development
    • Pipeline summary
  • Lacosamide
    • Profile
      • Drug overview: unknown mode of action
    • Clinical trial data
      • Clinical trial 1: Phase III trial for lacosamide in epilepsy.
      • Preliminary data from additional Phase III trials
    • Patient potential
    • Marketing factors
      • Co-marketing will increase uptake
      • Schwarz' s presence in the CNS market is increasing
    • Satisfaction of unmet needs
      • Reported efficacy in treating refractory partial epilepsy patients is encouraging
      • Unreported side-effect profile
      • Lack of teratogenicity in animal studies
    • Forecasts to 2015
    • Datamonitor drug assessment summary
  • Brivaracetam
    • Profile
      • Drug overview: orally active ligand of synaptic vesicle protein 2A (SV2A)
    • Clinical trial data
      • Clinical trial 1: Phase II study in Keppra refractory patients
      • Clinical trial 2: Smaller Phase II study investigating a higher dose of brivaracetam
      • Clinical trial 3: Phase IIb head-to-head with levetiracetam (Keppra)
    • Patient potential
    • Marketing potential
      • Commercial value of pursuing Unverricht-Lundborg disease indication
      • Can UCB bring both Keppra follow-on drugs to market at the same time?
      • Long patent life for brivaracetam and seletracetam could keep UCB as a leading company on the AED market for many years
      • UCB' s epilepsy franchise strategy
    • Forecasts to 2015
      • UCB' s epilepsy franchise will continue to grow throughout the forecast period if Schwarz' s pipeline AED lacosamide is incorporated into UCB' s portfolio
    • Datamonitor drug assessment summary
  • Seletracetam
    • Profile
      • Drug overview: high-affinity synaptic vesicle glycoprotein (SV2A)
      • UCB' s reformulation strategy differs between seletracetam and brivaracetam
  • YKP-509
    • Profile
      • Drug overview: unknown mechanism of action
  • Soretolide (D-2916)
    • Profile
      • Drug overview: unknown mechanism of action
  • Valrocemide (TVP-1901)
    • Profile
      • Drug overview: glycine derivative of valproic acid
• CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS
  • Key Phase I and preclinical antiepileptic compounds
    • Broad range of physiological targets being investigated in early-stage development
    • CGX-1007
      • Drug overview
      • Mechanism of action
      • Anticonvulsant potential
      • Alliances and collaborations
      • Datamonitor comment
    • Isovaleramide (NPS-1776)
      • Drug overview
      • Mechanism of action
      • Anticonvulsant potential
      • Alliances and collaborations
      • Datamonitor comment
  • Key research impacts on epilepsy
    • Genomics and proteomics might provide researchers with animal models mimicking refractory epilepsy
• BIBLIOGRAPHY
  • Journal articles and conference abstracts
  • Websites
• APPENDIX A
  • Forecast revenues
  • Competitive positioning analysis of pipeline epilepsy drugs
  • Contributing experts
• APPENDIX B
  • Methodology
    • Definition of epilepsy market
    • Datamonitor forecast methodology
      • Product forecasts
      • Sales calculations
      • Definition of a standard unit
      • Japanese market data
    • Additional information
  • About Datamonitor
    • About Datamonitor Healthcare
    • Datamonitor Healthcare' s therapy area capabilities
    • About the CNS analysis team
  • Disclaimer
  • List of Tables
    • Table 1: Prevalence of epilepsy across the seven major markets, 2006
    • Table 2: Different seizure types and their typical characteristics
    • Table 3: KOL estimates of the proportion of partial seizure subtypes
    • Table 4: Factors leading to noncompliance to AED treatment in patients with epilepsy
    • Table 5: Responder rates for key pipeline and comparator drugs in refractory partial epilepsy
    • Table 6: Key pipeline drug in preregistration for the treatment of epilepsy, 2006
    • Table 7: Key pipeline drugs in Phase III development for the treatment of epilepsy, 2006
    • Table 8: Key pipeline drugs in Phase II development for the treatment of epilepsy, 2006
    • Table 9: Investigated epilepsy types for key pipeline AEDs, 2006
    • Table 10: UCB' s AED portfolio, 2006
    • Table 11: Eisai' s AED portfolio, 2006
    • Table 12: Additional therapeutic indications approved and sought by marketed AEDs, 2006
    • Table 13: Additional therapeutic indications sought by pipeline drugs, 2006
    • Table 14: Advantages and disadvantages of off-label prescribing
    • Table 15: Only one key product in late-stage R&D pipeline in the GABAergic modulator drug class, 2006
    • Table 16: Key events, approvals and launch dates impacting DP-VPA' s revenue forecast, 2006-2015
    • Table 17: Key products in late-stage R&D pipeline of the ion channel modulator drug class, 2006
    • Table 18: Key approvals and launch dates impacting rufinamide' s revenue forecast, 2006-2015
    • Table 19: Key events and assumptions impacting retigabine' s revenue forecast, 2006-2015
    • Table 20: Key events and assumptions impacting Lamictal' s (IR and XR) revenue forecast, 2006-2015
    • Table 21: Discontinued R&D project, 2006
    • Table 22: Key products in late-stage R&D pipeline of the glutamate modulator drug class, 2006
    • Table 23: Key events and assumptions impacting Ampanel' s revenue forecast, 2006-2015
    • Table 24: Discontinued R&D project, 2006
    • Table 25: Key products in late-stage R&D pipeline of other drug classes, 2006
    • Table 26: Key events and assumptions impacting lacosamide' s revenue forecast, 2006-2015
    • Table 27: Key events and assumptions impacting the combined revenue forecast of brivaracetam and seletracetam, 2006-2015
    • Table 28: Key drugs in Phase I development for epilepsy, 2006
    • Table 29: Key drugs in preclinical development for epilepsy, 2006
    • Table 30: Datamonitor' s forecast epilepsy revenues of pipeline drugs and the total epilepsy market across the seven major markets ($m), 2007-2015
    • Table 31: Summary of commercial and research/clinical attractiveness of late-stage drugs for epilepsy
    • Table 32: ICD-10 codes used to size the epilepsy market
  • List of Figures
    • Figure 1: Datamonitor' s epilepsy market summary, 2005-2015
    • Figure 2: Datamonitor epilepsy drug assessment summary
    • Figure 3: Incidence of epilepsy by seizure type
    • Figure 4: Incidence of epilepsy in different age groups
    • Figure 5: Summary of the major unmet needs in the treatment of epilepsy, 2006
    • Figure 6: Drug classes in development for the treatment of epilepsy, 2006
    • Figure 7: Datamonitor' s forecast of epilepsy sales for the pipeline AED DP-VPA across the seven major markets ($m), 2006-2015
    • Figure 8: Datamonitor' s competitive positioning analysis for DP-VPA, 2006-2015
    • Figure 9: Datamonitor' s forecast of epilepsy sales for the pipeline AED rufinamide across the seven major markets ($m), 2006-2015
    • Figure 10: Datamonitor' s competitive positioning analysis for rufinamide, 2006-2015
    • Figure 11: Datamonitor' s forecast of epilepsy sales for the pipeline AED retigabine across the seven major markets ($m), 2006-2015
    • Figure 12: Datamonitor' s competitive positioning analysis for retigabine, 2006-2015
    • Figure 13: Datamonitor' s forecast of combined epilepsy sales for Lamictal IR and XR across the seven major markets ($m), 2006-2015
    • Figure 14: Datamonitor' s forecast of epilepsy sales for the pipeline AED Ampanel across the seven major markets ($m), 2006-2015
    • Figure 15: Datamonitor' s competitive positioning analysis for Ampanel, 2006-2015
    • Figure 16: Datamonitor' s forecast of epilepsy sales for the pipeline AED lacosamide across the seven major markets ($m), 2006-2015
    • Figure 17: Datamonitor' s competitive positioning analysis for lacosamide, 2006-2015
    • Figure 18: Datamonitor' s forecast of the combined sales for the pipeline AED brivaracetam and seletracetam in epilepsy across the seven major markets ($m), 2006-2015
    • Figure 19: UCB' s potential epilepsy franchise, 2005-2015
    • Figure 20: Datamonitor' s combined competitive positioning analysis for brivaracetam and seletracetam, 2006-2015