Pipeline Insight: Epilepsy - Pipeline drugs struggle to outshine their marketed predecessors
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the epilepsy market - page 5
- Summary - page 6
- CHAPTER 2 PATIENT POTENTIAL - page 21
- Definition of epilepsy - page 22
- Etiology of epilepsy - page 22
- Diagnosis of epilepsy - page 23
- Epidemiology of epilepsy - page 26
- Segmentation of epilepsy - page 28
- Seizures are categorized according to their location of origin - page 28
- Little difference in prevalence of partial and generalized epilepsy - page 30
- Incidence of epilepsy peaks in early and late life - page 33
- Seizures are categorized according to their location of origin - page 28
- Unmet need in epilepsy - page 34
- Unmet need 1: Efficacious treatments for refractory epilepsy - page 36
- Unmet need 2: Reduction in adverse side effects - page 37
- Unmet need 3: Greater treatment options for elderly patients - page 38
- Unmet need 4: Greater treatment options for pediatric epilepsy - page 39
- Unmet need 5: Compliance - page 40
- Unmet need 6: Non-teratogenic treatments for use in pregnancy - page 41
- Unmet need 7: AEDs which do not react with oral contraception - page 42
- Definition of epilepsy - page 22
- CHAPTER 3 R&D APPROACH - page 44
- Classification of pipeline products - page 45
- GABA modulators - page 46
- Ion channel modulators - page 47
- Glutamate modulators - page 48
- Others - page 48
- Clinical trial design in epilepsy - page 50
- 'Add-on' studies are the mainstay in clinical trial design - page 50
- Clinical trial endpoints in epilepsy - page 51
- Post-marketing studies are important for detecting rare adverse events - page 53
- Key difficulties in epilepsy clinical trials - page 54
- Heterogeneity of disease - page 54
- Wide use of patients' self-reporting - page 54
- Applicability of trial results to the elderly population - page 54
- Clinical trial design guidance from the EMEA - page 55
- Current gold standard and comparator therapies - page 56
- Gold standard epilepsy therapy unclear - page 56
- Gold standard for partial epilepsy - page 56
- Gold standard for generalized seizures - page 57
- UCB's Keppra is the comparator drug for new entrants - page 58
- Numerous indication expansions in the last year - page 58
- Comparison of responder rates for key pipeline, the comparator drug (Keppra) and other marketed AEDs in refractory partial epilepsy - page 59
- Classification of pipeline products - page 45
- CHAPTER 4 EPILEPSY PIPELINE ANALYSIS - page 60
- Pipeline overview - page 61
- Drugs in preregistration - page 61
- Pipeline drugs in Phase III - page 62
- Pipeline drugs in Phase II - page 63
- Investigated epilepsy types for each key pipeline drug - page 64
- Key companies involved in the epilepsy pipeline - page 65
- UCB - page 65
- Development of a drug with a novel mode of action and specific focus on epilepsy was a winning strategy for UCB - page 65
- Keppra contributes over half of the revenue gained by UCB's CNS franchise - page 66
- UCB's AED portfolio - page 67
- Will UCB follow the same strategies in the future? - page 67
- Eisai - page 68
- Eisai's CNS strategy is one of inlicensing AEDs - page 68
- Overview of Eisai's CNS franchise - page 68
- Eisai's AED portfolio - page 69
- UCB - page 65
- Strategies for success - page 71
- Reformulations - page 71
- Drug delivery methods - page 71
- Chemical reformulations - page 73
- Indication expansion - page 73
- Drug versatility in the treatment of epilepsy - page 73
- Targeting additional therapeutic indications - page 74
- Bipolar disorder treatment is a lucrative market for anticonvulsants - page 77
- Regulatory approval or off-label prescribing? - page 77
- Reformulations - page 71
- Pipeline overview - page 61
- CHAPTER 5 GABAERGIC MODULATORS: LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 79
- Overview of GABAergic drugs - page 80
- Pipeline summary - page 80
- DP-VPA - page 81
- Profile - page 81
- Drug overview: currently in Phase II for severe forms of epilepsy - page 81
- Clinical data - page 82
- Clinical trial 1: Phase II trials of DP-VPA. - page 82
- Clinical trial 2: Phase I clinical trial data were presented at the Fourth and Fifth Eilat conferences - page 83
- Patient potential - page 83
- Marketing factors - page 84
- Satisfaction of unmet needs - page 84
- Primary benefit would be in an improved side-effect profile - page 84
- Forecasts to 2015 - page 85
- Datamonitor drug assessment summary - page 87
- Profile - page 81
- Overview of GABAergic drugs - page 80
- CHAPTER 6 ION CHANNEL MODULATORS: LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 88
- Overview of Ion channel modulator drugs - page 89
- Pipeline summary - page 89
- Rufinamide - page 90
- Profile - page 90
- Drug overview: currently in preregistration for LGS and adjunctive therapy for partial onset seizures - page 90
- Clinical data - page 91
- Clinical trial 1: The effect of the new antiepileptic drug rufinamide on cognitive functions - page 91
- Clinical trial 2: Efficacy and safety of rufinamide adjunctive therapy in patients with Lennox-Gastaut syndrome. - page 92
- Clinical trial 3: Rufinamide: a double-blind placebo-controlled proof of principle trial in patients with epilepsy - page 93
- Clinical trial 4: Efficacy and safety of rufinamide as adjunctive therapy in adult patients with therapy-resistant partial-onset seizures - page 94
- Preliminary data presented at the 8th Eilat Conference on New Antiepileptic Drugs - page 94
- Patient potential - page 95
- Potential in partial seizures is limited - page 95
- Add-on rather than switching from other therapies - page 95
- High potential for share of the Lennox-Gastaut Syndrome market - page 96
- Marketing factors - page 98
- Expansion outside the domestic market - page 98
- Launch in an under-developed Japanese market - page 98
- Increasing focus of epilepsy treatment - page 99
- Launch of specialized CNS sales force - page 100
- Off-label use following license in Lennox-Gastaut syndrome - page 100
- Satisfaction of unmet needs - page 100
- Additional treatment option for pediatric patients - page 100
- Forecasts to 2015 - page 101
- Datamonitor drug assessment summary - page 103
- Profile - page 90
- Retigabine - page 104
- Profile - page 104
- Drug overview: potassium channel opener currently in Phase III development - page 104
- Clinical data - page 104
- Clinical trial 1: Phase II studies of retigabine in epilepsy. - page 104
- Clinical trial 2: Multiple-dose, linear, dose-proportional pharmacokinetics or retigabine in healthy volunteers. - page 105
- Phase II safety studies - page 106
- Additional pharmacokinetic Phase I trials investigating drug interactions with retigabine - page 106
- Ongoing clinical trials - page 107
- Patient potential - page 107
- Marketing factors - page 107
- Valeant has some CNS sales and marketing experience, but a co-marketing deal will be required to realize retigabines revenue generating potential - page 108
- Satisfaction of unmet needs - page 108
- Adverse side-effects may be a concern - page 108
- Similar efficacy for refractory patients as current drugs - page 109
- Patient compliance may be an issue with a three-times a day treatment - page 109
- No reported interactions with oral contraception - page 110
- Forecasts to 2015 - page 110
- Datamonitor drug assessment summary - page 112
- Profile - page 104
- Lamictal XR - page 113
- Profile - page 113
- Drug overview: extended release formulation of currently available treatment - page 113
- Clinical trial data - page 113
- Ongoing clinical trials - page 114
- NCT00113165: Study evaluating Lamictal extended-release therapy added to current seizure treatments in patients with partial seizures. - page 114
- NCT00104416: Study evaluating Lamictal extended-release therapy added to current seizure treatments in patients with Primary Generalized Tonic-Clonic (PGTC) seizures - page 114
- NCT00355082: Conversion to monotherapy with Lamictal extended-release tablets for treatment of partial epilepsy - page 115
- Patient potential - page 115
- Marketing factors - page 115
- GSK has had varying success with this type of lifecycle management strategy in the past - page 116
- Following initial high uptake, Paxil CR did not significantly help GSK maintain market share with Paxil - page 116
- Successive launches of Wellbutrin reformulations has helped maintain market share following an initial slump - page 116
- Will Lamical follow the Paxil or Wellbutrin model? - page 117
- Satisfaction of unmet needs - page 118
- Theoretically the side-effect profile may be improved over Lamictal IR - page 118
- Patient compliance may not be increased due to once-a-day dosing regime - page 119
- Forecasts to 2015 - page 120
- Datamonitor drug assessment summary - page 121
- Profile - page 113
- Late-stage products recently discontinued - page 122
- Overview of Ion channel modulator drugs - page 89
- CHAPTER 7 GLUTAMATE MODULATORS: LATE-STAGE ANALYSIS AND FORECASTS - page 123
- Overview of glutamate modulator drugs - page 124
- Pipeline summary - page 124
- E-2007 - page 124
- Profile - page 124
- Drug overview: AMPA glutamate receptor antagonist - page 124
- Profile - page 124
- NS-1209 - page 126
- Profile - page 126
- Drug overview: AMPA glutamate receptor and metabotropic glutamate receptor antagonist - page 126
- Profile - page 126
- Ampanel (talampanel) - page 127
- Profile - page 127
- Drug overview: non-competitive AMPA receptor antagonist - page 127
- Clinical data - page 127
- Clinical trial 1: Clinical trial data presented at the seventh Eilat Conference on New Antiepileptic Drugs in Sardinia, Italy (May 2004). - page 127
- Clinical trial 2: A crossover, add-on trial of talampanel in patients with refractory partial seizures. - page 128
- Patient potential - page 129
- Marketing factors - page 129
- Satisfaction of unmet needs - page 130
- No significant efficacy for complex partial seizures - page 130
- Weak side-effect profile in Phase II study - page 130
- Forecasts to 2015 - page 131
- Datamonitor drug assessment summary - page 133
- Profile - page 127
- Late-stage products recently discontinued - page 134
- Overview of glutamate modulator drugs - page 124
- CHAPTER 8 OTHER LATE-STAGE PRODUCTS IN CLINICAL DEVELOPMENT - page 135
- Overview of the other AEDs in late-stage development - page 136
- Pipeline summary - page 136
- Lacosamide - page 136
- Profile - page 136
- Drug overview: unknown mode of action - page 136
- Clinical trial data - page 137
- Clinical trial 1: Phase III trial for lacosamide in epilepsy. - page 137
- Preliminary data from additional Phase III trials - page 138
- Patient potential - page 139
- Marketing factors - page 139
- Co-marketing will increase uptake - page 140
- Schwarz's presence in the CNS market is increasing - page 140
- Satisfaction of unmet needs - page 141
- Reported efficacy in treating refractory partial epilepsy patients is encouraging - page 141
- Unreported side-effect profile - page 142
- Lack of teratogenicity in animal studies - page 142
- Forecasts to 2015 - page 143
- Datamonitor drug assessment summary - page 145
- Profile - page 136
- Brivaracetam - page 146
- Profile - page 146
- Drug overview: orally active ligand of synaptic vesicle protein 2A (SV2A) - page 146
- Clinical trial data - page 147
- Clinical trial 1: Phase II study in Keppra refractory patients - page 147
- Clinical trial 2: Smaller Phase II study investigating a higher dose of brivaracetam - page 148
- Clinical trial 3: Phase IIb head-to-head with levetiracetam (Keppra) - page 148
- Patient potential - page 149
- Marketing potential - page 150
- Commercial value of pursuing Unverricht-Lundborg disease indication - page 150
- Can UCB bring both Keppra follow-on drugs to market at the same time? - page 150
- Long patent life for brivaracetam and seletracetam could keep UCB as a leading company on the AED market for many years - page 151
- UCB's epilepsy franchise strategy - page 151
- Forecasts to 2015 - page 153
- UCB's epilepsy franchise will continue to grow throughout the forecast period if Schwarz's pipeline AED lacosamide is incorporated into UCB's portfolio - page 155
- Datamonitor drug assessment summary - page 156
- Profile - page 146
- Seletracetam - page 157
- Profile - page 157
- Drug overview: high-affinity synaptic vesicle glycoprotein (SV2A) - page 157
- UCB's reformulation strategy differs between seletracetam and brivaracetam - page 158
- Profile - page 157
- YKP-509 - page 158
- Profile - page 158
- Drug overview: unknown mechanism of action - page 158
- Profile - page 158
- Soretolide (D-2916) - page 160
- Profile - page 160
- Drug overview: unknown mechanism of action - page 160
- Profile - page 160
- Valrocemide (TVP-1901) - page 160
- Profile - page 160
- Drug overview: glycine derivative of valproic acid - page 160
- Profile - page 160
- Overview of the other AEDs in late-stage development - page 136
- CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS - page 162
- Key Phase I and preclinical antiepileptic compounds - page 163
- Broad range of physiological targets being investigated in early-stage development - page 163
- CGX-1007 - page 166
- Drug overview - page 166
- Mechanism of action - page 166
- Anticonvulsant potential - page 167
- Alliances and collaborations - page 167
- Datamonitor comment - page 168
- Isovaleramide (NPS-1776) - page 168
- Drug overview - page 168
- Mechanism of action - page 168
- Anticonvulsant potential - page 169
- Alliances and collaborations - page 169
- Datamonitor comment - page 170
- Key research impacts on epilepsy - page 170
- Genomics and proteomics might provide researchers with animal models mimicking refractory epilepsy - page 170
- Key Phase I and preclinical antiepileptic compounds - page 163
- BIBLIOGRAPHY - page 172
- Journal articles and conference abstracts - page 172
- Websites - page 178
- APPENDIX A - page 183
- Forecast revenues - page 183
- Competitive positioning analysis of pipeline epilepsy drugs - page 184
- Contributing experts - page 185
- APPENDIX B - page 186
- Methodology - page 186
- Definition of epilepsy market - page 186
- Datamonitor forecast methodology - page 187
- Product forecasts - page 187
- Sales calculations - page 187
- Definition of a standard unit - page 187
- Japanese market data - page 187
- Additional information - page 188
- About Datamonitor - page 188
- About Datamonitor Healthcare - page 188
- Datamonitor Healthcare's therapy area capabilities - page 189
- About the CNS analysis team - page 190
- Disclaimer - page 191
- Methodology - page 186
- List of Tables
- Table 1: Prevalence of epilepsy across the seven major markets, 2006 - page 27
- Table 2: Different seizure types and their typical characteristics - page 29
- Table 3: KOL estimates of the proportion of partial seizure subtypes - page 32
- Table 4: Factors leading to noncompliance to AED treatment in patients with epilepsy - page 41
- Table 5: Responder rates for key pipeline and comparator drugs in refractory partial epilepsy - page 59
- Table 6: Key pipeline drug in preregistration for the treatment of epilepsy, 2006 - page 61
- Table 7: Key pipeline drugs in Phase III development for the treatment of epilepsy, 2006 - page 62
- Table 8: Key pipeline drugs in Phase II development for the treatment of epilepsy, 2006 - page 63
- Table 9: Investigated epilepsy types for key pipeline AEDs, 2006 - page 64
- Table 10: UCB's AED portfolio, 2006 - page 67
- Table 11: Eisai's AED portfolio, 2006 - page 69
- Table 12: Additional therapeutic indications approved and sought by marketed AEDs, 2006 - page 75
- Table 13: Additional therapeutic indications sought by pipeline drugs, 2006 - page 76
- Table 14: Advantages and disadvantages of off-label prescribing - page 78
- Table 15: Only one key product in late-stage R&D pipeline in the GABAergic modulator drug class, 2006 - page 80
- Table 16: Key events, approvals and launch dates impacting DP-VPA's revenue forecast, 2006-2015 - page 86
- Table 17: Key products in late-stage R&D pipeline of the ion channel modulator drug class, 2006 - page 89
- Table 18: Key approvals and launch dates impacting rufinamide's revenue forecast, 2006-2015 - page 102
- Table 19: Key events and assumptions impacting retigabine's revenue forecast, 2006-2015 - page 111
- Table 20: Key events and assumptions impacting Lamictal's (IR and XR) revenue forecast, 2006-2015 - page 121
- Table 21: Discontinued R&D project, 2006 - page 122
- Table 22: Key products in late-stage R&D pipeline of the glutamate modulator drug class, 2006 - page 124
- Table 23: Key events and assumptions impacting Ampanel's revenue forecast, 2006-2015 - page 132
- Table 24: Discontinued R&D project, 2006 - page 134
- Table 25: Key products in late-stage R&D pipeline of other drug classes, 2006 - page 136
- Table 26: Key events and assumptions impacting lacosamide's revenue forecast, 2006-2015 - page 144
- Table 27: Key events and assumptions impacting the combined revenue forecast of brivaracetam and seletracetam, 2006-2015 - page 154
- Table 28: Key drugs in Phase I development for epilepsy, 2006 - page 163
- Table 29: Key drugs in preclinical development for epilepsy, 2006 - page 164
- Table 30: Datamonitor's forecast epilepsy revenues of pipeline drugs and the total epilepsy market across the seven major markets ($m), 2007-2015 - page 183
- Table 31: Summary of commercial and research/clinical attractiveness of late-stage drugs for epilepsy - page 184
- Table 32: ICD-10 codes used to size the epilepsy market - page 186
- List of Figures
- Figure 1: Datamonitor's epilepsy market summary, 2005-2015 - page 6
- Figure 2: Datamonitor epilepsy drug assessment summary - page 7
- Figure 3: Incidence of epilepsy by seizure type - page 31
- Figure 4: Incidence of epilepsy in different age groups - page 33
- Figure 5: Summary of the major unmet needs in the treatment of epilepsy, 2006 - page 35
- Figure 6: Drug classes in development for the treatment of epilepsy, 2006 - page 46
- Figure 7: Datamonitor's forecast of epilepsy sales for the pipeline AED DP-VPA across the seven major markets ($m), 2006-2015 - page 85
- Figure 8: Datamonitor's competitive positioning analysis for DP-VPA, 2006-2015 - page 87
- Figure 9: Datamonitor's forecast of epilepsy sales for the pipeline AED rufinamide across the seven major markets ($m), 2006-2015 - page 101
- Figure 10: Datamonitor's competitive positioning analysis for rufinamide, 2006-2015 - page 103
- Figure 11: Datamonitor's forecast of epilepsy sales for the pipeline AED retigabine across the seven major markets ($m), 2006-2015 - page 110
- Figure 12: Datamonitor's competitive positioning analysis for retigabine, 2006-2015 - page 112
- Figure 13: Datamonitor's forecast of combined epilepsy sales for Lamictal IR and XR across the seven major markets ($m), 2006-2015 - page 120
- Figure 14: Datamonitor's forecast of epilepsy sales for the pipeline AED Ampanel across the seven major markets ($m), 2006-2015 - page 131
- Figure 15: Datamonitor's competitive positioning analysis for Ampanel, 2006-2015 - page 133
- Figure 16: Datamonitor's forecast of epilepsy sales for the pipeline AED lacosamide across the seven major markets ($m), 2006-2015 - page 143
- Figure 17: Datamonitor's competitive positioning analysis for lacosamide, 2006-2015 - page 145
- Figure 18: Datamonitor's forecast of the combined sales for the pipeline AED brivaracetam and seletracetam in epilepsy across the seven major markets ($m), 2006-2015 - page 153
- Figure 19: UCB's potential epilepsy franchise, 2005-2015 - page 155
- Figure 20: Datamonitor's combined competitive positioning analysis for brivaracetam and seletracetam, 2006-2015 - page 156
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