Report: Pipeline Insight: Epilepsy - Pipeline drugs struggle to outshine their marketed predecessors TOC

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

Pipeline Insight: Epilepsy - Pipeline drugs struggle to outshine their marketed predecessors

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