パーキンソン病：治療の進行に必要な神経防護作用

Abstract

Overview

Introduction

Parkinson' s disease (PD) is a progressive, degenerative condition of the central nervous system that affects the way the brain coordinates body movements, including walking, talking and writing. PD affects less than 1% of the population in the seven major markets (7MM); with patients typically being diagnosed in their early sixties and living for over 18 years after the onset of first symptoms.

Scope

• Overview of epidemiology, presentation, and diagnostic assessment in PD
• Breakdown of first-line treatment regimens for early-, mid-, and advanced-stage disease, with analysis of second-line add-on and switching dynamics
• Influences on neurologists' treatment decisions and their perception of current brands
• Evaluation of treatment outcomes and surgical procedures for PD

Highlights

Neurologists indicated that the DAs Mirapex (pramipexole) and Requip (ropinirole) are generally the initial treatment of choice for younger presenting patients. While levodopa is reserved for patients over 65 years of age, neurologists may prescribe the MAOIs selegiline and rasagiline (Azilect) in young patients with only mild symptoms at onset.

Neurologists indicated that only 36% of advanced-stage PD patients are adequately controlled by pharmacological therapy. Considering the even distribution of patient severities (30% early-stage, 39% mid-stage and 31% advanced-stage), the advanced-stage patient group is particularly poorly served by current therapies.

Neurologists estimated that approximately 9% of all PD patients will eventually require surgery. Deep Brain Stimulation is by far the most common surgical procedure used in the 7MM and neurologists indicated that over 70% of patients receiving it experience both a reduction in PD symptoms and a reduction in the dose of pharmacological medication.

Reasons to Purchase

• Target prescribers more effectively, through an understanding of prescribing behavior and its influences
• Validate new product forecasting based on diagnosis and treatment rates, and the likely rate of uptake for new products
• Benchmark brand awareness and perceptions surrounding product positioning in order to formulate competitive lifecycle management strategies

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the central nervous system pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Datamonitor insight into the Parkinson' s disease market
  • Contributing experts
  • Related reports
• CHAPTER 2 INTRODUCTION AND SCOPE
  • Coverage of the Stakeholder Insight Survey
    • Disease definition and epidemiology
    • Presentation, diagnosis and comorbidities
    • Pharmacological treatment trends
    • Key prescribing influences
    • Treatment outcomes and surgery
  • Future trends
• CHAPTER 3 COUNTRY TREATMENT TREES
  • Introduction to treatment trees
  • First-line treatment trees
    • US
    • Japan
    • France
    • Germany
    • Italy
    • Spain
    • UK
  • Second-line treatment trees
    • US
    • Japan
    • France
    • Germany
    • Italy
    • Spain
    • UK
• CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION
  • Disease definition
    • The etiology of PD is not yet clear
    • Parkinson' s disease is typically classified by the Hoehn and Yahr scale
      • Patient population is generally well spread across the three disease severities
  • Epidemiology of Parkinson' s disease
    • Parkinson' s disease rarely affects adults younger than 50 years of age
    • Prevalence of Parkinson' s disease
      • Over 1.4 million individuals across the US, Japan and 5EU are estimated to suffer from PD
    • European and Japanese epidemiology studies
      • Italy
      • UK
      • Japan
• CHAPTER 5 PRESENTATION, DIAGNOSIS AND COMORBIDITIES
  • Presentation
    • Time to presentation
      • Early symptoms are generally very subtle and often go unnoticed
    • Improving presentation rates
      • Internet and patient advocacy groups are essential awareness drivers
      • Improved education of the public and primary care physicians is needed
    • The four common presentations of PD
      • Tremor
      • Rigidity
      • Akinesia and bradykinesia
      • Postural instability
  • Diagnosis
    • An accurate diagnosis of PD comes from combined neurological, laboratory and imaging evaluations
      • Neurological evaluation of PD
      • Laboratory evaluation of PD
      • Imaging studies for PD
    • Delays in the diagnosis of PD
      • Misdiagnosis is as high as 20-30% in the early stages
      • It takes on average 13 weeks from presentation to a physician to an accurate diagnosis of PD
      • Differential diagnosis to rule out other possible neurological conditions
    • More than half of prevalent early-stage PD patients remain undiagnosed
    • Over 80% of patients are characterized as having either early- or mid-stage PD at diagnosis
  • Comorbidities (non-motor symptoms) of PD
    • Depression is the most common comorbidity at each stage of the disease
      • Depression
      • Dementia
      • Psychosis
      • Sleep disturbances
• CHAPTER 6 TREATMENT OPTIONS AND GUIDELINES
  • Treatment options
    • Non-pharmacological treatment
      • Non-pharmacological only approaches are largely shelved once mid-stage PD is reached
    • Pharmacological treatment
      • Dopaminergics
      • Dopamine agonists
      • Catechol-O-methyltransferase inhibitors
      • Monoamine oxidase inhibitors
      • Other treatments
    • Surgical treatment
      • Surgery becomes an option when PD symptoms cannot be adequately controlled with medication
      • Deep brain stimulation is now the current standard surgical practice for PD
      • Duodopa pump provides continuous dopaminergic stimulation
  • Treatment guidelines
    • The treatment of PD is a highly individualized process
    • US-guidelines based on AAN recommendations
      • New guidelines issued by the AAN in 2006 are more proscriptive than prescriptive
    • UK-National Institute for Health and Clinical Excellence guidelines
      • Recommended pharmacological therapy in early PD
      • Recommended pharmacotherapy in later PD
      • Guidance on surgery for PD
    • Other guidelines by region
• CHAPTER 7 PRESCRIBING TRENDS IN PARKINSON' S DISEASE
  • Pharmacological prescribing trends
    • Caveats-prescribing trends
    • Seven major market overview of prescribing trends
      • A greater proportion of patients progress to second-line therapy as the disease severity advances
    • Physician type responsible for initial prescription of PD therapy
      • Neurologists make the majority of initial treatment decisions for PD in the 7MMs
    • Role of pharmacological treatment in the management of PD
      • UK neurologists report waiting the longest period of time before initiating pharmacological therapy once early-stage PD has been diagnosed
      • Pharmacological therapy is not deemed essential in patients characterized as having early-stage PD
      • Pharmacological and non-pharmacological therapy is combined in more than half of all advanced-stage PD patients in Germany and the UK
    • Prescribing trends in early-stage PD
      • The proposed neuroprotective properties of the MAO-B inhibitors and dopamine agonists are still to be proven
      • Age and symptom severity dictates first-line therapy decisions
      • Boehringer Ingelheim' s pramipexole (Mirapex) leads the way in first-line early-stage PD management
      • Initiation of pharmacological therapy with levodopa remains high
      • First-line selegiline monotherapy is rarely seen
      • Monotherapy largely dominates early-stage PD management
      • Some 40% of early-stage patients progress to second-line therapy within 20 months
      • 60% of early-stage PD patients who progress to second-line therapy have a drug added-on to their first-line regimen
      • Levodopa-carbidopa or levodopa monotherapy are the most commonly added-on products at second-line for early-stage PD
      • Pramipexole and ropinirole are the most common second-line regimens switched to at early-stage
    • Prescribing trends in mid-stage PD
      • Fixed-dose combinations containing levodopa and dopamine agonist therapy make up first-line therapy for mid-stage PD
      • Levodopa-carbidopa therapy is prescribed first-line to a fifth of all mid-stage PD patients in the US
      • Over half of all mid-stage PD patients receive combination therapy
      • 50% of mid-stage patients progress to second-line therapy within 2 years
      • Adding-on accounts for the greater proportion of second-line dynamics for mid-stage PD
      • Entacapone is the most commonly added-on therapy at second-line in mid-stage PD
      • Second-line mid-stage PD sees like-for-like dopamine agonist switching and movement towards more complex fixed-dose combination products
    • Prescribing trends in advanced-stage PD
      • Levodopa-carbidopa fixed-dose combination products dominate first-line therapy for advanced PD
      • Monotherapy is rare in advanced-stage PD
      • Over 70% of UK patients progress to second-line therapy for advanced-stage PD
      • Neurologists continue to add-on therapy in the majority of advanced PD cases
      • Amantadine and rasagiline are highly popular add-ons in second-line for advanced PD
      • Apomorphine adding-on is highest in France and Spain
      • Levodopa-benserazide viewed as a second-line alternative to levodopa-carbidopa
• CHAPTER 8 PRESCRIBING INFLUENCES AND BRAND ASSESSMENT
  • Factors influencing physician decision making
    • Side-effect profile is the number one influential factor
      • Mid- and advanced-stage pharmacotherapy is governed by managing the side effects of levodopa
      • Dopamine agonist side effects are mostly cognitive in nature
    • A drugs ability to reduce OFF periods has a high influence on prescribing decisions
      • The goals of therapy are to reduce OFF periods as much as possible
    • Ability to minimize dyskinesias was rated the most influential attribute in Japan
    • Ability to use as either monotherapy or adjunctive therapy becomes more influential as the disease progresses
    • Ability to delay the use of levodopa therapy influences only initial treatment decisions
    • Ability to enhance the benefit of levodopa therapy has led to the development of a number of products
  • Physician perception of key brands
    • Neurologists in Japan are most satisfied with current therapies
    • Interpreting a brand map
    • Brand comparison shows levodopa remains the "gold standard" symptomatic PD treatment
      • Sinemet (carbidopa-levodopa)
      • Parcopa (carbidopa-levodopa)
      • Madopar (levodopa-benserazide)
      • Stalevo (carbidopa-levodopa-entacapone)
    • The dopamine agonists and now Azilect continue to battle it out for market position
      • Requip (ropinirole)
      • Mirapex (pramipexole)
      • Neupro (rotigotine)
      • Apokyn (apomorphine)
      • Azilect (rasagiline)
      • Comtan (entacapone)
• CHAPTER 9 TREATMENTS OUTCOMES AND SURGERY
  • Treatment outcomes
    • Only 36% of advanced-stage patients are adequately controlled by pharmacological therapy
    • Intolerable side effects are the key reason for discontinuing or switching treatment
      • Although pill burden affects patient quality of life, it has a low influence on discontinuing or switching therapies
  • Surgical treatment of Parkinson' s disease
    • Progression to surgery
      • More than half of the 9% of PD patients who require surgery go on to receive it
      • The invasive nature of surgical techniques limits their use
    • Surgical techniques used
      • Deep Brain Stimulation is by far the most common surgical technique used across the seven major markets
    • Outcome of surgery
      • Over 50% of patients will experience both a reduction in PD symptoms and a reduction in the dose of pharmacological medication with each surgical technique
• BIBLIOGRAPHY
  • Journal papers
  • Websites
• APPENDIX A
  • Physician research methodology
    • Physician sample breakdown
      • US
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
  • Contributing experts
• APPENDIX B
  • The survey questionnaire
    • Physician' s details
    • Screening questions
    • INTRODUCTION
    • Section 1-Patient segmentation and diagnosis of Parkinson' s disease
    • Section 2-Treatment of Parkinson' s disease
      • Early-stage pharmacological treatment
      • Mid-stage pharmacological treatment
      • Advanced-stage pharmacological treatment
    • Section 3-Key prescribing factors
    • Section 4-Treatment outcomes and Surgery
    • Demographics
  • Disclaimer
  • List of Tables
    • Table 1: The five stages of PD according to the Hoehn and Yahr scale
    • Table 2: Prevalence of PD across the seven major markets, 2007
    • Table 3: Unified Parkinson' s Disease Rating Scale-cognition, behavior and mood
    • Table 4: Proportion of prevalent PD population diagnosed at each disease stage across the seven major markets, 2007
    • Table 5: Options for initial pharmacotherapy in early PD as proposed in NICE guidelines, 2006
    • Table 6: Options for adjuvant pharmacotherapy in later PD as proposed in NICE guidelines, 2006
    • Table 7: Percentage of interviewed neurologists selecting each regimen as a first-line therapy for early-stage PD, 2007
    • Table 8: Early-stage PD second-line therapy patient progression details, 2007
    • Table 9: Percentage of drugs added-on at second-line to the dopamine agonists selected for first-line early-stage PD therapy across the seven major markets, 2007
    • Table 10: Most common selected second-line regimens after switching from first-line dopamine agonist monotherapy for early-stage PD across the seven major markets, 2007
    • Table 11: Percentage of interviewed neurologists selecting each regimen as a first-line therapy for mid-stage PD, 2007
    • Table 12: Percentage of patients receiving each drug regimen as first-line for mid-stage PD, 2007
    • Table 13: Mid-stage PD second-line therapy patient progression details, 2007
    • Table 14: Advanced-stage PD second-line therapy patient progression details, 2007
    • Table 15: Factors that influence drug choice for the management of PD, 2007
    • Table 16: Number and percentage of neurologists able to rate each brand
    • Table 17: Overall performance of each Parkinson' s disease drug against six attributes according to interviewed neurologists in the seven major markets, 2007
    • Table 18: The overall performance of each drug against all attributes, and with attribute weightings applied
    • Table 19: Sinemet' s attribute scores, by country
    • Table 20: Comparison of Parcopa' s and Sinemet' s US attribute scores
    • Table 21: Madopar' s attribute scores, by country
    • Table 22: Stalevo' s attribute scores, by country
    • Table 23: Requip' s attribute scores, by country
    • Table 24: Mirapex' s attribute scores, by country
    • Table 25: Neupro' s attribute scores, by country
    • Table 26: Apokyn' s attribute scores, by country
    • Table 27: Treatment-emergent adverse events (incidence ≥10%) and associated rate of discontinuation during open-label long-term use of Apokyn (n=550)
    • Table 28: Azilect' s attribute scores, by country
    • Table 29: Comtan' s attribute scores, by country
    • Table 30: Reasons for patients discontinuing a therapy/switching to an alternative drug therapy on a scale of 1 to 10, where 1=factor of low influence and 10=factor of high influence, 2006
    • Table 31: US-physician sample breakdown, 2007
    • Table 32: Japan-physician sample breakdown, 2007
    • Table 33: France-physician sample breakdown, 2007
    • Table 34: Germany-physician sample breakdown, 2007
    • Table 35: Italy-physician sample breakdown, 2007
    • Table 36: Spain-physician sample breakdown, 2007
    • Table 37: UK-physician sample breakdown, 2007
  • List of Figures
    • Figure 1: Diagrammatic overview of the coverage of the Stakeholder Insight: Parkinson' s Disease survey, 2007
    • Figure 2: Parkinson' s disease treatment tree split by disease severity in the US, 2007
    • Figure 3: Parkinson' s disease treatment tree split by disease severity in Japan, 2007
    • Figure 4: Parkinson' s disease treatment tree split by disease severity in France, 2007
    • Figure 5: Parkinson' s disease treatment tree split by disease severity in Germany, 2007
    • Figure 6: Parkinson' s disease treatment tree split by disease severity in Italy, 2007
    • Figure 7: Parkinson' s disease treatment tree split by disease severity in Spain, 2007
    • Figure 8: Parkinson' s disease treatment tree split by disease severity in the UK, 2007
    • Figure 9: Second-line early-stage Parkinson' s disease treatment dynamics in the US, 2007
    • Figure 10: Second-line mid-stage Parkinson' s disease treatment dynamics in the US, 2007
    • Figure 11: Second-line advanced-stage Parkinson' s disease treatment dynamics in the US, 2007
    • Figure 12: Second-line early-stage Parkinson' s disease treatment dynamics in Japan, 2007
    • Figure 13: Second-line mid-stage Parkinson' s disease treatment dynamics in Japan, 2007
    • Figure 14: Second-line advanced-stage Parkinson' s disease treatment dynamics in Japan, 2007
    • Figure 15: Second-line early-stage Parkinson' s disease treatment dynamics in France, 2007
    • Figure 16: Second-line mid-stage Parkinson' s disease treatment dynamics in France, 2007
    • Figure 17: Second-line advanced-stage Parkinson' s disease treatment dynamics in France, 2007
    • Figure 18: Second-line early-stage Parkinson' s disease treatment dynamics in Germany, 2007
    • Figure 19: Second-line mid-stage Parkinson' s disease treatment dynamics in Germany, 2007
    • Figure 20: Second-line advanced-stage Parkinson' s disease treatment dynamics in Germany, 2007
    • Figure 21: Second-line early-stage Parkinson' s disease treatment dynamics in Italy, 2007
    • Figure 22: Second-line mid-stage Parkinson' s disease treatment dynamics in Italy, 2007
    • Figure 23: Second-line advanced-stage Parkinson' s disease treatment dynamics in Italy, 2007
    • Figure 24: Second-line early-stage Parkinson' s disease treatment dynamics in Spain, 2007
    • Figure 25: Second-line mid-stage Parkinson' s disease treatment dynamics in Spain, 2007
    • Figure 26: Second-line advanced-stage Parkinson' s disease treatment dynamics in Spain, 2007
    • Figure 27: Second-line early-stage Parkinson' s disease treatment dynamics in the UK, 2007
    • Figure 28: Second-line mid-stage Parkinson' s disease treatment dynamics in the UK, 2007
    • Figure 29: Second-line advanced-stage Parkinson' s disease treatment dynamics in the UK, 2007
    • Figure 30: Proportion of diagnosed PD patients suffering from each disease severity, 2007
    • Figure 31: PD progression timeline from onset of early-stage disease to death as indicated by interviewed neurologists, 2007
    • Figure 32: Age at diagnosis for each stage of PD, 2007
    • Figure 33: Average time in months from the onset of symptoms of PD to initial presentation to a physician, 2007
    • Figure 34: Percentage of neurologists using each diagnostic imaging technique to make a diagnosis of PD, 2007
    • Figure 35: The number of weeks between presentation to a physician and an accurate diagnosis of PD, 2007
    • Figure 36: Percentage of prevalent PD population diagnosed vs undiagnosed for each disease stage, 2007
    • Figure 37: Proportion of interviewed neurologists' PD patients characterized as having each stage of the disease, 2007
    • Figure 38: Proportion of interviewed neurologists' PD patients with each severity of the disease at initial diagnosis, 2007
    • Figure 39: Proportion of PD patients suffering with each comorbidity at the three stages of the disease, 2007
    • Figure 40: Mean percentage of pharmacological and non-pharmacological PD therapy across the seven major markets, 2007
    • Figure 41: Mechanism of action of levodopa therapy
    • Figure 42: Mechanism of action of AADC inhibitors (DDIs)
    • Figure 43: Mechanism of action of COMT inhibitor (entacapone)
    • Figure 44: Mechanism of action of MAO-B inhibitors
    • Figure 45: Pharmacological treatment algorithm for PD
    • Figure 46: The dynamics of pharmacological treatment in PD management, 2007
    • Figure 47: Physician type breakdown of the initial treatment decision of PD in the seven major markets, 2007
    • Figure 48: Weeks between diagnosis of PD and the initiation of pharmacological therapy by disease stage, 2007
    • Figure 49: Percentage of patients receiving pharmacological therapy for PD across the seven major markets by stage, 2007
    • Figure 50: Percentage of patients receiving pharmacological and non-pharmacological therapy for PD across the seven major markets by stage, 2007
    • Figure 51: Early-stage second-line management strategies for pramipexole across the seven major markets, 2007
    • Figure 52: First-line treatment regimens for early-stage PD in the seven major markets, 2007
    • Figure 53: Monotherapy vs combination therapy split for early-stage PD management, 2007
    • Figure 54: Patients who progress to second-line early-stage PD therapy and receive add-on or are switched, 2007
    • Figure 55: Second-line drug add-ons for early-stage PD in the seven major markets, 2007
    • Figure 56: Most common drug regimens switched to at second-line for early-stage PD across the seven major markets, 2007
    • Figure 57: Mid-stage second-line management strategies for levodopa-carbidopa (Sinemet, Parcopa) across the seven major markets, 2007
    • Figure 58: First-line treatment regimens for mid-stage PD in the seven major markets, 2007
    • Figure 59: Monotherapy and combination therapy split for mid-stage PD management, 2007
    • Figure 60: Patients who progress to second-line mid-stage PD therapy and receive add-on or switch, 2007
    • Figure 61: Second-line drug add-ons for mid-stage PD in the seven major markets, 2007
    • Figure 62: Most common drug regimens switched to at second-line for mid-stage PD across the seven major markets, 2007
    • Figure 63: Advanced-stage second-line management strategies for levodopa-carbidopa (Sinemet, Parcopa) across the seven major markets, 2007
    • Figure 64: First-line treatment regimens for advanced-stage PD in the seven major markets, 2007
    • Figure 65: Monotherapy and combination therapy split for advanced-stage PD management, 2007
    • Figure 66: Patients who progress to second-line advanced-stage PD therapy and receive add-on or switch, 2007
    • Figure 67: Second-line drug add-ons for advanced-stage PD in the seven major markets, 2007
    • Figure 68: Number of times neurologists added on Apokyn in second-line for advanced-stage PD across the seven major markets, 2007
    • Figure 69: Most common drug regimens switched to at second-line for advanced-stage PD across the seven major markets, 2007
    • Figure 70: Average rating of factors which influence drug choice for the management of PD, 2007
    • Figure 71: Neurologist' s scores of side-effect profile, by brand
    • Figure 72: Importance of a drug' s ability to minimize dyskinesias on prescribing decisions by country, 2007
    • Figure 73: Overview brand map of attributes versus brand perception
    • Figure 74: Physician perception of levodopa-based combination products
    • Figure 75: Levodopa-based combination brand map of attributes versus brand perception
    • Figure 76: PD-specific Sinemet sales, 2003-06
    • Figure 77: Sinemet map, country preference to prescribing attributes
    • Figure 78: PD-specific Madopar sales, 2003-06
    • Figure 79: Madopar' s attribute scores, by country
    • Figure 80: PD-specific Stalevo sales, 2003-06
    • Figure 81: Stalevo' s attribute scores, by country
    • Figure 82: Proportion of patients receiving Stalevo at first-line for each stage of PD, 2007
    • Figure 83: Physician perception of the dopamine agonists, Azilect and Comtan
    • Figure 84: Non-levodopa containing product brand map of attributes versus brand perception
    • Figure 85: PD-specific Requip sales, 2003-06
    • Figure 86: Requip' s overall attribute scores
    • Figure 87: PD-specific Mirapex sales, 2003-06
    • Figure 88: Mirapex and Requip overall attribute scores
    • Figure 89: Diagrammatic representation of Neupro' s mode of action
    • Figure 90: PD-specific quarterly Neupro sales in Germany, Spain and the UK, Q3-2006-Q2-2007
    • Figure 91: Country rating of Neupro, Requip and Mirapex on the ability to use as either monotherapy or adjunctive therapy
    • Figure 92: Proportion of patients receiving Neupro at first-line for each stage of PD, 2007
    • Figure 93: Apokyn' s overall attribute scores
    • Figure 94: PD- specific quarterly US Apokyn sales, Q1 2006-Q2 2007
    • Figure 95: PD- specific Azilect sales, H2 2005-H1 2007
    • Figure 96: Percentage of patients adequately controlled by pharmacological therapy at each stage of the disease as indicated by interviewed neurologists across the seven major markets, 2007
    • Figure 97: Percentage of PD patients requiring and receiving surgery across the seven major markets, 2007
    • Figure 98: Ratings of the reasons why patients do not receive surgery in the seven major markets, 2007
    • Figure 99: Percentage of neurologists with patients who receive surgery utilizing each PD surgical technique, 2007
    • Figure 100: Percentage of patients who undergo surgery and receive each surgical technique, 2007
    • Figure 101: Mean percentage of patients for whom each surgical technique results in a reduction in Parkinson' s disease symptoms and a reduction in the dose of pharmacological medication across the seven major markets, 2007