Market Report Source

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