Market Report Source

Overview

Introduction

Despite affecting a large number of individuals, there are currently no treatments capable of curing either Parkinson’s disease or Restless Legs Syndrome. Although available treatments are effective, numerous unmet needs prevail. Several compounds are in late-stage development and are forecast to achieve sales of $519m for Parkinson’s disease and $399m for Restless Legs Syndrome in 2015.

Scope

*Analysis of patient potential, unmet needs and clinical trial design in Parkinson’s disease and Restless Legs Syndrome across the US, EU and Japan *Overview of drugs in pre-registration, Phase III, II, I and preclinical development; with analysis of key companies involved in the market *Detailed profiles of key compounds in development for Parkinson’s disease and Restless Legs Syndrome, with forecasts of drug revenues to 2015 *Discussion of innovative early stage products and insight from key industry opinion leaders

Highlights

Dopamine agonists with alternative delivery systems are expected to drive near-term changes in the Parkinson’s disease market. While Schwarz’s rotigotine patch holds several advantages over current oral treatments its success looks set to be eclipsed by GSK’s once-daily tablet, Requip Modutab, which is forecast to reach peak sales of $543m in 2011.

The mid-stage pipeline for Parkinson’s disease is unimpressive, with a host of potential neuroprotectants failing to demonstrate conclusive benefits in slowing disease progression. The most exciting near-term prospects are likely to come from cell and gene therapy products such as Titan/Schering’s Spheramine or Avigen’s AV-201.

The recent approval of the dopamine agonists Requip and Mirapex for Restless Legs Syndrome have provided a viable treatment option. However, unmet needs still exist and treatments, such as XenoPort’s XP13512 which offer alternative mechanisms to dopaminergic stimulation may provide greater symptomatic benefit to current treatments.

Reasons to Purchase

*Understand unmet needs in the Parkinson’s disease and Restless Legs Syndrome market based on key opinion leader comments *Benchmark key late-stage Parkinson’s disease and Restless Legs Syndrome compounds against current market leaders *Assess the global sales forecasts of late-stage pipeline drugs; and examine their clinical and commercial potential

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the CNS pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the Parkinson’s disease and Restless Legs Syndrome market

CHAPTER 2 PATIENT POTENTIAL- PARKINSON’S DISEASE

Definition of Parkinson’s disease

The etiology of PD is not yet clear

Segmentation of Parkinson’s disease

Parkinson’s disease is typically classified by the Hoehn & Yahr scale

Epidemiology of Parkinson’s disease

Demographics provide baseline sales growth

Several comorbid disorders are thought to result from neurodegeneration in PD

Sleep disorders are most common in advanced PD

Depression in PD has both psychological and pathological causes

Dementia in PD becomes more likely as the disease progresses

Psychosis is both a feature of PD and a side effect of treatment

New tools are improving diagnosis

Treatment strategies in Parkinson’s disease

Unmet needs in Parkinson’s disease

Drugs that slow or prevent disease progression

Reduction of motor complications

Motor fluctuations

Dyskinesias

Other motor complications

Smoother levodopa dosage

Lower side effects

Reduce pill burden

Reduce time to levodopa therapy

Lower cost

CHAPTER 3 PARKINSON’S DISEASE R&D APPROACH

Classification of marketed and pipeline products

Market definition for this report

Dopaminergics

Levodopa still considered most effective agent for reducing PD symptoms

Dopamine agonists

Dopamine agonists considered first line therapy

Mirapex (pramipexole) the market leading dopamine agonist

Neupro (rotigotine CDS) offers an alternative delivery method

Apokyn (apomorphine) helps niche patient cohort

Several dopamine agonists with novel delivery systems are in development

Catechol-O-methyltransferase inhibitors

Comtan (entacapone) is the market leading COMT-inhibitor

Stalevo reduces pill burden

Monoamine oxidase inhibitors

Selegiline has an established role in the treatment of early PD

Zelapar (selegiline; orally disintegrating tablets) may offer advantages over conventional selegiline

Azilect (rasagiline) has recently received approval for early and late stage PD

Safinamide is the only MAOI in late stage development

Other marketed therapies

Anticholinergics provide little interest for developers of new treatments

N-methlyl-D-aspartate receptor antagonists may hold further potential

Novel therapies

The potential for adenosine A2a receptor antagonists remains unclear

Neuroprotectants aim to slow or stop the progression of PD

Cell/ gene therapies are designed to make up for the loss of neurons in PD

Clinical trial design in Parkinson’s disease

Neuroprotection clinical trial design continues to present challenges

At risk patients are ideal for studies but are difficult to recruit

Choice of clinical endpoints in neuroprotective studies depends on the population studied

Futility studies help determine which agents to select for further study

Delayed start design aims to separate symptomatic from neuroprotective effect of a study agent

Clinical trial endpoints in Parkinson’s disease

Decreased latency to ON time, increased ON time, and decreased OFF time are key endpoints for EU and US approval

Unified Parkinson’s Disease Rating Scale offers a more comprehensive measure of PD progression

Cognition, behavior and mood- Part I of the UPDRS

Activities of daily living- Part II of the UPDRS

Motor examination- Part III of the UPDRS

Gold standard therapies for Parkinson’s disease

CHAPTER 4 PARKINSON’S DISEASE PIPELINE ANALYSIS

Pipeline overview

Late-stage pipeline overview

Registration overview

Pre-registration overview

Phase III overview

Phase II overview

Key companies involved in the Parkinson’s disease pipeline

Big Pharma need to increase investment into drug discovery projects for disease modifying agents

Pfizer

The symptomatic treatment market provides opportunities for specialty companies

Vernalis

CHAPTER 5 DOPAMINERGICS- LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview of the dopaminergic class

Pipeline summary

V1512 (melevodopa-carbidopa)

Drug overview

Clinical trials

Phase II/III trials conducted by Chiesi

Ongoing Phase III trials

Pharmacokinetic study

Patient potential

Marketing factors

Further Datamonitor comments

Satisfaction of unmet needs

Reduction of dyskinesia or OFF time

Smoother levodopa dosage

Reduce pill burden

Lower cost

Forecasts to 2015

Datamonitor does not expect V1512 to gain significant sales from current treatments

V1512 is at risk of generic entacapone from 2010

CHAPTER 6 DOPAMINE AGONISTS- LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview of the dopamine agonists class

Pipeline summary

Requip Modutab (ropinirole XL 24 hour)

Clinical trials

Ongoing Phase III comparison with immediate release ropinirole

Patient population

Marketing factors

Satisfaction of unmet needs

Reduction of dyskinesia or OFF time

Lower side effects

Reduce pill burden

Reduce time to levodopa therapy

Lower cost

Forecasts to 2015

Datamonitor expects Requip Modutab to limit the success of Neupro

Generic ropinirole is set to limit the success of Requip Modutab

SLV-308

Drug overview

Ongoing Phase III clinical trials

S308.3.001/ S308.3.003- SLV-308 in treatment of patients with early PD

Ascending dose tolerability/ safety study in advanced PD with levodopa

Patient potential

Marketing factors

Datamonitor comments

Forecasts to 2015

The role of SLV308 is not yet clear and forecast sales are low

Other drugs in the dopamine agonist class

Lisuride (TTS/ SubQ)

Lisuride TTS

Lisuride (SubQ)

Datamonitor comments

Rotigotine nasal spray

Apomorphine nasal powder

AMR-101 (apomorphine sublingual)

CHAPTER 7 ADENOSINE A2A RECEPTOR ANTAGONISTS- LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview of the adenosine A2a receptor antagonist class

Pipeline summary

KW-6002 (istradefylline)

Drug overview

Completed Phase III trials

Study 6002-US-018- 10, 20, 40mg/day KW-6002 in combination

Study 6002-US-013- 20mg/day KW-6002 in combination

Study 6002-EU-007- 40mg/day KW-6002 in combination

Completed Phase II trials

Study 6002-US-001- 20, 40mg/day KW-6002 in combination

Ongoing trials

Study 6002-US-051- Phase II monotherapy in early PD

Study 6002-0406- Phase II Japan- 20, 40mg/day KW-6002 in combination

Study 6002-0407- Phase II Japan- early PD

Study 6002-INT-001- long-term safety

Study 6002-US-025- long-term safety

Patient population

Marketing factors

Further Datamonitor comments

Satisfaction of unmet needs

Reduction of dyskinesia or OFF time

Lower side effects

Reduce pill burden

Reduce time to levodopa therapy

Lower cost

Forecasts to 2015

KW-6002 may provide a novel mechanism for treating ‘wearing off’

KW-6002 sales are expected to depend on the success of E2007

Approval in Japan and use in early PD may support sales growth

Other drugs in the adenosine A2a receptor antagonist class

Fipamezole (JP-1730)

Clinical trials

Sch-58261 analog

CHAPTER 8 MAOIS- LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview of the MAOI class

Pipeline summary

Safinamide (NW-1015)

Drug overview

Phase III clinical trials

Adjunctive treatment to dopamine agonists in patients with early-stage PD.

Phase II trials

Safinamide as an adjunct to a dopamine agonist in early PD.

Phase I trials

Patient potential

Marketing factors

Datamonitor comments

Satisfaction of unmet needs

Drugs that slow or prevent disease progression

Reduction of dyskinesia or OFF time

Reduce pill burden

Lower cost

Forecasts to 2015

Safinamide’s benefits over current MAOIs are unclear

The ADAGIO study of Azilect will set the first hurdle for safinamide in neuroprotection

CHAPTER 9 NEUROPROTECTANTS- LATE STAGE DRUG ANALYSIS

Overview of the neuroprotectant class

Pipeline summary

Definition of current comparator therapy

SR57667

Ongoing clinical trials

EFC5287- Phase II study of SR57667 on the progression of PD

ACT5288- Study of SR57667 on 18F-Dopa PET imaging in PD patients

Further Datamonitor comments

PD-02 (creatine)

Phase II clinical trials

Phase II futility study of PD-02 in early PD

Cereact Capsule (ONO-2506PO)

Drug overview

Clinical trials

Phase II study of ONO-2506PO in patients with PD in Japan.

Datamonitor comments

GM1 ganglioside

Drug overview

Clinical trials

Phase II study of GM1 ganglioside in mild to moderate PD

Second Phase II study of GM1 ganglioside in mild to moderate PD

Kinampa (talampanel)

Drug overview

Clinical trials

Phase II study of talampanel on dyskinesias associated with treatment of patients with advanced PD

NINDS sponsored Phase II study of talampanel

FP-0011

Late-stage development compounds recently discontinued

GPI-1485

Phase II study- Guildford Pharmaceuticals/ Amgen

Phase II study- Guildford/ SNDC

Phase II study- NINDS

CHAPTER 10 CELL/GENE THERAPY- LATE STAGE PRODUCT ANALYSIS

Overview of the cell/gene therapy class

Pipeline summary

Definition of current comparator therapy

Spheramine (RPE cell therapy)

Drug overview

Clinical trials

Phase I/II open-label study

The STEPS trial- Phase II double-blind study

Further Datamonitor comments

AV201 (AAV-AADC)

Drug overview

Clinical trials

Phase I/II increasing dose trial

CHAPTER 11 OTHERS- LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview of the others class

Pipeline summary

E2007

Drug overview

Completed Phase II trials

Study 204- Phase IIb proof-of-concept

Ongoing Phase III trials

Study E2007-E044-301- E2007 in levodopa treated PD patients with motor fluctuations

Patient potential

Marketing factors

Further Datamonitor comments

Satisfaction of unmet needs

Reduction of dyskinesia or OFF time

Lower side effects

Lower cost