Pipeline Insight: Epilepsy - Past successes hard to emulate in highly genericized market

Pipeline Insight: Epilepsy - Past successes hard to emulate in highly genericized market published by Datamonitor in May, 2010. This report consists of Pages: 166 and the price starts from US $ 11400.

Introduction

Abstract

Introduction

Sales of antiepileptic drugs totaled $3.5 billion in 2009 across the seven major markets (US, Japan, France, Germany, Italy, Spain and the UK). Datamonitor anticipates the combination of continuing strong historical growth dynamics and the uptake of the late-stage pipeline drugs to result in the market value peaking at $5.1 billion in 2017, after which a new wave of patent expiries hits the US.

Scope

• Analysis of current epilepsy treatments, unmet market needs and the impact of generics.
• Review of the late-stage epilepsy pipeline, including analysis of key R&D company strategies.
• In depth analysis of historic (2005-2009) and future (2010-2019) seven major market sales value dynamics.
• Commercial and clinical assessment of key late-stage pipeline drugs, with key opinion leader comment and region-specific sales forecasts to 2019.

Highlights

With more convenient dosing and a purported improved safety profile over Trileptal and Tegretol, Stedesa (eslicarbazepine, Sepracor/Eisai) is forecast to become the best-selling pipeline antiepileptic drug. Factoring monotherapy approval and first-line use, epilepsy-specific sales are forecast to top $400m across the seven major markets by 2019.

Rikelta (brivaracetam, UCB) is forecast to generate almost $375m by 2019. With to UCB' s already extensive epilepsy portfolio, Datamonitor expects careful positioning will negate significant sales cannibalization. Use will be chiefly among refractory patients with partial seizures, with monotherapy approval important to commercial success.

Three products are in late-stage development for the at-home management of acute seizures, a market dominated by Diastat (diazepam rectal gel, Valeant). With all seeking to provide an improved administration method, Ikano' s intranasal midazolam (ITI-111) is set to become the new market leader with approximately $30m in sales by 2019.

Reasons to Purchase

• Analyze competitive environment at time of product launch.
• Validate internal forecasts and market potential for pipeline products.
• Identify licensing opportunities based on company portfolio and market needs.

Table of Contents

Overview

• Catalyst
• Summary
• About Datamonitor Healthcare
• About the central nervous system pharmaceutical analysis team
• Executive Summary
• Strategic scoping and focus
• Datamonitor insight into the epilepsy market
• Related reports
• Upcoming related reports
• Table of Contents

1. Pipeline Overview and Dynamics

• Key findings
• Pipeline overview
• Epilepsy pipeline shows moderate innovation
• Classification of pipeline products
• GABA enhancers and ion channel modulators account for two-thirds of the late-stage epilepsy pipeline
• Investigated epilepsy types for each key pipeline drug
• Adjunctive therapy for refractory partial seizures is typically the initial indication
• Comparative forecasts
• Pipeline compounds from traditional classes to boost market sales
• Late-stage compounds in development set to achieve significant market share
• Datamonitor' s pipeline assessment summary
• Keppra remains the drug to beat, even 10 years after initial approval
• Key companies involved in the epilepsy pipeline
• UCB
• A novel mode of action and specific focus on epilepsy was a winning strategy for UCB
• UCB' s market leader status in epilepsy will be maintained by reformulations and successors to Keppra
• Eisai
• Eisai follows a strategy of in-licensing antiepileptic drugs
• Key R&D company strategies
• Reformulations
• Extended-release formulations have dominated historical drug delivery advancements
• Minor chemical alterations are employed to improve efficacy or reduce side effect issues
• Indication expansion
• Monotherapy approval remains ultimate goal but niche pediatric indications represent additional opportunities
• Targeting additional central nervous system therapeutic indications is a common strategy
• Bipolar disorder and neuropathic pain markets prove lucrative for antiepileptic drugs

2. Disease Overview - Market Potential

• Key findings
• Definition
• Etiology of epilepsy
• Diagnosis of epilepsy
• Patient segmentation
• Seizures are categorized according to their location of origin
• Incidence of epilepsy
• There is little difference in the prevalence of partial and generalized epilepsy
• Incidence of epilepsy peaks in early and later years of life
• Epidemiology
• Seven major markets
• Almost 5 million individuals are estimated to suffer from epilepsy in the seven major markets
• Rest of the world
• China and India both have sizable epileptic populations each in excess of 6 billion
• Current treatment options
• A plethora of antiepileptic drugs are available but no true broad spectrum agent exists
• Impact of generic erosion
• The switching of stable epilepsy patients to a generic alternative remains controversial
• Switching between multiple generic formulations poses a danger
• Generic antiepileptic drugs-when used correctly-offer a benefit
• Current gold standard and comparator therapies
• Keppra shows broad spectrum activity and a strong safety profile
• Current market overview
• Epilepsy market struck by US patent expiry of key brands
• Total market volume increases despite drop in value
• Antiepileptic drugs fall broadly into two classes based on growth rate
• Unmet needs in epilepsy
  • Unmet need 1: efficacious treatments for refractory epilepsy
  • Unmet need 2: reduction in adverse side effects
  • Unmet need 3: greater understanding of pediatric epilepsy
  • Unmet need 4: greater treatment options for elderly patients
  • Unmet need 5: compliance
• Target product profile versus current level of attainment

3. R&D Approach

• Key findings
• Clinical trial design in epilepsy
• ' Add-on' studies are the mainstay of clinical trial design
• Clinical trial endpoints in epilepsy
• Other measures focus on wider aspects of life quality
• 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
• Japanese clinical trials
• Changing clinical trials methods contribute to a chasm between Japanese and Western epilepsy markets
• Clinical trial design guidance from the EMA
• The typical Phase III clinical trial

4. Pipeline Analysis & Forecasts: Ion channel modulators

• Key findings
• Overview for ion channel modulators
• Pipeline summary
• Comparative forecasts
• Stedesa/Zebinix (eslicarbazepine acetate, Sepracor/Eisai/Bial Group)
• Drug overview
• US approval expected to follow 2009 EU approval
• Drug profile
• Clinical trial data
• Stedesa has demonstrated impressive efficacy in reducing partial-onset seizures in refractory patients
• SWOT analysis
• Datamonitor' s drug assessment scorecard for Stedesa
• Clinical and commercial attractiveness
• Despite strong trial results, Stedesa may suffer from heavy competition and the lack of distinction from the other dibenzazepines
• Satisfaction of unmet needs
• Stedesa will offer clear benefit should trial results transpire in practice
• Forecasts to 2019
• Stedesa set to achieve significant commercial success, dependent on monotherapy approval
• Retigabine (D-23129, Valeant Pharmaceuticals/GlaxoSmithKline)
• Drug overview
• First-in-class ion channel modulator retigabine is pending approval in US and Europe
• Drug profile
• Clinical trial data
• Despite high discontinuation rate, retigabine responded "almost ideally" in Phase III clinical trials
• SWOT analysis
• Datamonitor' s drug assessment scorecard for retigabine
• Clinical and commercial attractiveness
• High incidence of minor side effects and three-times daily dosing offsets promising efficacy
• Satisfaction of unmet needs
• Retigabine offers benefit for treatment-refractory patients
• Forecasts to 2019
• Sizable market share for retigabine despite use being limited to adjunctive therapy
• Epliga (controlled-release oxcarbazepine, Supernus Pharmaceuticals)
• Drug overview
• Supernus claims alleviation of side effects and more convenient dosing for Epliga over Trileptal
• Drug profile
• Clinical trial data
• Lack of publicly available clinical data for Epliga
• SWOT analysis
• Datamonitor' s drug assessment scorecard for Epliga
• Clinical and commercial attractiveness
• Epliga' s appeal is heavily affected by lack of novelty and strong competition
• Satisfaction of unmet needs
• Epliga provides little breakthrough in the current treatment paradigm
• Forecasts to 2019
• Epliga to occupy small niche in market
• Other drugs in ion channel modulation
• Captisol-enabled fosphenytoin (CyDex Pharmaceuticals)
• Late-stage development compounds recently discontinued
• Comfyde (carisbamate, Johnson & Johnson)
• Key early-stage compounds in ion channel modulation
• ICA-105665 (Icagen)
• Retigabine MR (Valeant Pharmaceuticals)
• Elpetrigine (JZP-4, Jazz Pharmaceuticals)

5. Pipeline Analysis & Forecasts: Glutamate modulators

• Key findings
• Overview for glutamate receptor modulators
• Pipeline summary
• Comparative forecast
• Perampanel (E2007, Eisai)
• Drug overview
• Global development of novel AMPA receptor antagonist perampanel in full swing
• Drug profile
• Clinical trial data
• Strong efficacy data but safety results conspicuous by their absence
• SWOT analysis
• Datamonitor' s drug assessment scorecard for perampanel
• Clinical and commercial attractiveness
• Perampanel is commercially appealing but the spotlight remains on its safety
• Satisfaction of unmet needs
• Perampanel seeks to address efficacy among refractory patients
• Forecasts to 2019
• Steady uptake of perampanel helped by geographical expansion
• Other drugs in glutamate modulation
• Topiramate reformulations
• Late-stage development compounds recently discontinued
• Talampanel (Eli Lilly, Teva Pharmaceuticals)
• Key early-stage compounds in glutamate modulation
• BGG492 (Novartis)

6. Pipeline Analysis & Forecasts: GABA modulators

• Key findings
• Overview for GABA receptor modulation
• Pipeline summary
• Comparative forecast
• Ganaxolone (Marinus Pharmaceuticals)
• Drug overview
• Innovative neurosteroid has potential broad-spectrum efficacy in epilepsy
• Drug profile
• Clinical trial data
• Synthetic neurosteroid ganaxolone is well tolerated
• SWOT analysis
• Datamonitor' s drug assessment scorecard for ganaxolone
• Clinical and commercial attractiveness
• Novelty should entice potential partners
• Satisfaction of unmet needs
• Ganaxolone shows a strong safety profile and may hold promise for refractory patients
• Forecasts to 2019
• Secondary indication to boost ganaxolone uptake
• Late-stage development compounds recently discontinued
• DP-VPA
• Key early-stage compounds in GABA modulation
• T2007 (sodium diphenyl barbiturate, Taro Pharmaceuticals)

7. Pipeline Analysis & Forecasts: Other antiepileptic drugs

• Key findings
• Overview for other antiepileptic drugs
• Pipeline summary
• Comparative forecast
• Rikelta (brivaracetam, UCB)
• Drug overview
• Rikelta is a second-generation SV2A ligand
• Drug profile
• Clinical trial data
• Rikelta' s progress slowed by mixed Phase III trial results
• SWOT analysis
• Datamonitor' s drug assessment scorecard for Rikelta
• Clinical and commercial attractiveness
• Rikelta will benefit from the positive image of UCB among neurologists, but needs to differentiate from Keppra
• Satisfaction of unmet needs
• Further clinical trials will expose Rikelta' s potential in refractory patients
• Forecasts to 2019
• Strong sales but Rikelta' s potential not fully realized
• Late-stage development compounds recently discontinued
• Seletracetam (UCB)
• Key other early-stage compounds
• VX-765 (Vertex Pharmaceuticals)
• JNJ-26489112 (Johnson & Johnson)
• YKP3089 (SK Life Science)

8. Pipeline Analysis & Forecasts: Acute epilepsy treatments

• Key findings
• Overview of acute epilepsy management
• Acute seizures are a serious medical crisis
• Gold standard for acute epilepsy management
• Diastat (diazepam rectal gel, Valeant)
• Unmet need in acute treatment of epilepsy
• Undesirable delivery of diazepam represents an unmet need in the acute setting
• Alternative methods for drug delivery
• Intranasal delivery is convenient, easy-to-use, effective and fast-acting
• Auto-injectors provide a reliable intramuscular route
• Pipeline summary
• Comparative forecast
• ITI-111 (midazolam intranasal, Ikano Therapeutics)
• Drug overview
• Datamonitor drug assessment scorecard for ITI-111
• Forecasts to 2019
• First-to-market ITI-111 to experience strong uptake
• JZP-8 (clonazepam intranasal, Jazz Pharmaceuticals)
• Drug overview
• Datamonitor drug assessment scorecard for JZP-8
• Forecasts to 2019
• Second-best for alternative intranasal treatment
• Vanquix (diazepam auto-injection, King Pharmaceuticals)
• Drug overview
• Datamonitor' s drug assessment scorecard for Vanquix
• Forecasts to 2019
• Success of Vanquix dependent on caregiver appeal of intramuscular injection

9. Innovative Early-Stage Approaches

• Key findings
• Medical devices in epilepsy
• Vagus nerve stimulation
• Cyberonics has produced the pioneering medical device in epilepsy
• Deep brain stimulation of thalamus
• Medtronic' s device is nearing FDA approval
• Responsive neurostimulation
• Innovative new system responds only to abnormal electric activity in addition to providing diagnostic information
• Intracranial drug delivery
• Targeted drug delivery could reduce broad side-effects associated with current drug therapies
• Future direction of epilepsy pharmacotherapy
• Metabolic regulation provides novel mode of action for small molecules
• 2-deoxy-D-glucose (NeuroGenomeX)
• Gene therapy can capitalize on endogenous seizure control systems
• Galanin (Asklepios BioPharmaceutical)
• Neuropeptide Y (Neurologix)
• Neuropeptides can be modified to improve pharmacokinetic profile
• NAX-5055 (NeuroAdjuvants)
• Adenosine-releasing implants
• Localized delivery avoids systemic side effects
• Bibliography
• Journal articles and conference abstracts
• Websites
• Datamonitor reports

APPENDIX

• Methodology
• Epidemiology estimate
• Definition of epilepsy market
• Product forecasts
• Sales calculations
• Definition of a standard unit
• Datamonitor' s drug assessment scorecard
• Contributing experts
• About Datamonitor
• About Datamonitor Healthcare
• About the Disease analysis team
• Datamonitor consulting
• Disclaimer

List of Tables

• Table 1: Key late-stage pipeline products in development for epilepsy, 2010
• Table 2: Investigated epilepsy types for key pipeline antiepileptic drugs, 2010
• Table 3: Sales forecasts for pipeline products in epilepsy in the seven major markets ($m), 2010-19
• Table 4: UCB' s antiepileptic drug portfolio, 2010
• Table 5: Eisai' s antiepileptic drug portfolio, 2010
• Table 6: Different seizure types and their typical characteristics
• Table 7: Prevalence of active epilepsy in the seven major markets (000s), 2010
• Table 8: Prevalence of epilepsy in the BRIC nations, Turkey and Canada (000s), 2010
• Table 9: Leading treatment options for epilepsy, 2010
• Table 10: Total healthcare costs of topiramate users, 2009
• Table 11: Keppra (levetiracetam) - drug profile, 2010
• Table 12: Ability of current class comparator to meet unmet needs in epilepsy, 2010
• Table 13: Typical Phase III clinical trial design in epilepsy
• Table 14: Ion channel modulator drugs in late-stage development for epilepsy, 2010
• Table 15: Sales forecasts for ion channel modulators in development for epilepsy in the seven major markets ($m), 2010-19
• Table 16: Stedesa - drug profile, 2010
• Table 17: Phase III clinical trials for eslicarbazepine acetate, 2008
• Table 18: Datamonitor' s drug assessment scorecard for Stedesa in epilepsy, 2010
• Table 19: Sales forecasts for Stedesa in the seven major markets ($m), 2010-19
• Table 20: Impacting factors on the revenue of Stedesa, 2010-19
• Table 21: Retigabine - drug profile, 2010
• Table 22: Phase III trial data for retigabine, 2008
• Table 23: Datamonitor' s drug assessment scorecard for retigabine in epilepsy, 2010
• Table 24: Sales forecasts for retigabine in the seven major markets ($m), 2010-19
• Table 25: Impacting factors on the revenue of retigabine, 2010-19
• Table 26: Epliga - drug profile, 2010
• Table 27: Key facts: Phase III trial of Epliga, 2010
• Table 28: Datamonitor' s drug assessment scorecard for Epliga in epilepsy, 2010
• Table 29: Sales forecasts for Epliga in the seven major markets ($m), 2010-19
• Table 30: Impacting factors on the revenue of Epliga, 2010-19
• Table 31: Glutamate modulator drugs in late-stage development for epilepsy, 2010
• Table 32: Sales forecasts for glutamate modulators in development for epilepsy in the seven major markets ($m), 2010-19
• Table 33: Perampanel - drug profile, 2010
• Table 34: Key facts: Phase III trial of perampanel, 2010
• Table 35: Datamonitor' s drug assessment scorecard for perampanel in epilepsy, 2010
• Table 36: Sales forecasts for perampanel in the seven major markets ($m), 2010-19
• Table 37: Impacting factors on the revenue of perampanel, 2010-19
• Table 38: GABA modulator drug in late-stage development for epilepsy, 2010
• Table 39: Sales forecasts for GABA modulators in development for epilepsy in the seven major markets ($m), 2010-19
• Table 40: Ganaxolone - drug profile, 2010
• Table 41: Key facts: Phase II trial of ganaxolone, 2010
• Table 42: Datamonitor' s drug assessment scorecard for ganaxolone in epilepsy, 2010
• Table 43: Sales forecasts for ganaxolone in the seven major markets ($m), 2010-19
• Table 44: Impacting factors on the revenue of ganaxolone, 2010-19
• Table 45: Other drugs in late-stage development for epilepsy, 2010
• Table 46: Sales forecasts for other drugs in development for epilepsy in the seven major markets ($m), 2010-19
• Table 47: Rikelta - drug profile, 2010
• Table 48: Phase II clinical trials for Rikelta, 2006
• Table 49: Datamonitor' s drug assessment scorecard for Rikelta in epilepsy, 2010
• Table 50: Sales forecasts for Rikelta in the seven major markets ($m), 2010-192010-19
• Table 51: Impacting factors on the revenue of Rikelta, 2010-19
• Table 52: Diastat (diazepam rectal gel) - drug profile, 2010
• Table 53: Treatments in late-stage development for acute epilepsy management, 2010
• Table 54: Sales forecasts for pipeline products in epilepsy in the US ($m), 2010-19
• Table 55: Datamonitor' s drug assessment scorecard for ITI-111 in acute epilepsy, 2010
• Table 56: Sales forecasts for ITI-111 in the seven major markets ($m), 2010-19
• Table 57: Impacting factors on the revenue of ITI-111, 2010-19
• Table 58: Datamonitor' s drug assessment scorecard for JZP-8 in acute epilepsy, 2010
• Table 59: Sales forecasts for JZP-8 in the seven major markets ($m), 2010-19
• Table 60: Impacting factors on the revenue of JZP-8, 2010-19
• Table 61: Datamonitor' s drug assessment scorecard for Vanquix in acute epilepsy, 2010
• Table 62: Sales forecasts for Vanquix in the seven major markets ($m), 2010-19
• Table 63: Impacting factors on the revenue of Vanquix, 2010-19
• Table 64: ICD-10 codes used to define the epilepsy market
• Table 65: Datamonitor' s drug assessment parameters for key late-stage epilepsy pipeline therapies
• Table 66: Datamonitor' s drug assessment parameters for key late-stage acute epilepsy pipeline therapies

List of Figures

• Figure 1: Late-stage epilepsy pipeline products by mode of action, 2010
• Figure 2: Typical modes of action in epilepsy pharmacotherapy
• Figure 3: Epilepsy-specific sales, historical and forecast to 2019, across the seven major markets
• Figure 4: Datamonitor' s pipeline assessment summary for epilepsy, 2010
• Figure 5: Additional indications of key approved and pipeline antiepileptic drugs, 2010
• Figure 6: Incidence of epilepsy by seizure type
• Figure 7: Incidence of epilepsy in different age groups
• Figure 8: Epilepsy population in Brazil, India, China and the US, 2010
• Figure 9: Epilepsy-specific sales value ($ billion) in the seven major markets by region, 2005-2009
• Figure 10: Epilepsy-specific sales volume (billion SUs) in the seven major markets by region, 2005-2009
• Figure 11: Epilepsy market mean prices split by region in the seven major markets, 2005-2009
• Figure 12: Performance of the top 10 brands in the seven major markets ($m), 2005-09
• Figure 13: Key unmet needs for epilepsy, 2010
• Figure 14: Ion channel modulators as antiepileptic drugs
• Figure 15: Datamonitor' s pipeline assessment summary for ion channel modulators in epilepsy, 2010
• Figure 16: Stedesa - SWOT analysis, 2010
• Figure 17: Datamonitor' s drug assessment summary for Stedesa in epilepsy, 2010
• Figure 18: Retigabine - SWOT analysis, 2010
• Figure 19: Datamonitor' s drug assessment summary for retigabine in epilepsy, 2010
• Figure 20: Epliga - SWOT analysis, 2010
• Figure 21: Datamonitor' s drug assessment summary for Epliga in epilepsy, 2010
• Figure 22: Glutamate receptor modulators as antiepileptic drugs
• Figure 23: Datamonitor' s drug assessment summary for glutamate modulators in epilepsy, 2010
• Figure 24: Perampanel - SWOT analysis, 2010
• Figure 25: Datamonitor' s drug assessment summary for perampanel in epilepsy, 2010
• Figure 26: GABA receptor modulators as antiepileptic drugs
• Figure 27: Datamonitor' s drug assessment summary for ganaxolone in epilepsy, 2010
• Figure 28: Ganaxolone - SWOT analysis, 2010
• Figure 29: Datamonitor' s drug assessment summary for ganaxolone in epilepsy, 2010
• Figure 30: Datamonitor' s drug assessment summary for other drugs in development for epilepsy, 2010
• Figure 31: Rikelta - SWOT analysis, 2010
• Figure 32: Datamonitor' s drug assessment summary for Rikelta in epilepsy, 2010
• Figure 33: Datamonitor' s pipeline assessment summary for acute antiepileptic therapies in epilepsy, 2010
• Figure 34: Possible inhibition of kindling progression by 2-deoxy-D-glucose in epilepsy
• Figure 35: Design of adenosine-releasing implants

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