Pipeline and Commercial Insight: Parkinson's Disease - Market to grow as first round of lifecycle management strategies succeed

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Central Nervous System pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Contributing experts
  • Datamonitor insight into the Parkinson' s disease market
  • Related reports
  • Upcoming related reports
• CHAPTER 2 MARKET OVERVIEW AND POTENTIAL
  • Market and disease definition
    • Parkinson' s disease overview
    • Definition of Parkinson' s disease market
  • Market potential
    • Epidemiology of PD
      • Prevalence of PD
      • Aging population provides baseline growth potential for PD
    • Unmet need in PD
      • Disease modifying treatments
      • Reduction of motor complications
      • Reduction in side effects
      • Reduced pill burden
      • Extended time to levodopa therapy
  • Current treatment classes and mechanisms
    • Treatment algorithm
    • Dopaminergics
      • Carbidopa adjunctive therapy
    • Dopamine agonists
      • Dopamine agonists move from adjunctive add-on to first-line therapy
    • Catechol-O-methyltransferase inhibitors
    • Monoamine oxidase inhibitors
    • Other treatments
      • Anticholinergics
      • NMDA receptor antagonist - amantadine
  • Market overview
    • PD market has grown over the last four years
      • The 5EU region generated more revenue from PD therapies than the US
    • PD market is set to grow throughout the forecast period
• CHAPTER 3 BRAND DYNAMICS AND LEADING COMPARATOR THERAPIES
  • Marketed brands overview
  • Mirapex (pramipexole)
    • Drug overview-market-leading dopamine agonist
    • Forecast
    • Clinical trial data
      • Pramipexole provides benefits over placebo in the treatment of early PD
      • Pramipexole also provides benefits over placebo as an adjunct to levodopa therapy in advanced PD
  • Neupro (rotigotine CDS)
    • Drug overview-moderate uptake of patch formulation dopamine agonist in the 5EU
    • Forecast
    • Clinical trial data
      • Dose-finding study SP 506 shows clear dose-dependent effect
      • Early PD-study SP512 and SP513
      • Phase III trials in advanced PD patients showed rotigotine to be safe and effective as adjunct to levodopa
  • Comtan (entacapone)
    • Drug overview-adjunctive therapy to levodopa
    • Forecast
    • Clinical trial data
      • Study 1-North America study (SEESAW) of entacapone in patients taking levodopa-carbidopa
      • Study 2-Nordic study (NOMECOMT) of entacapone in patients taking levodopa-carbidopa
      • Study 3-German-Austrian study of entacapone in patients taking levodopa-carbidopa
  • Stalevo
    • Drug overview - combination of entacapone, carbidopa and levodopa
    • Forecast
  • Selegiline and its many reformulations
    • Drug overview-highly genericized molecule
  • Azilect (rasagiline)
    • Drug overview-has recently received approval for early- and late-stage PD
    • Forecast
    • Clinical trial data
      • TEMPO study-rasagiline as a monotherapy in early PD
      • TEMPO study-12 months open-label follow-up
      • LARGO study-rasagiline as an adjunctive treatment in moderate-to-advanced PD
      • PRESTO study-adjunctive treatment in moderate-to-advanced PD patients with motor complications
    • Ongoing trial-ADAGIO disease progression
• CHAPTER 4 FORECAST ANALYSIS
  • Key events
    • New product launches
      • Requip Modutab extended release
      • Istradefylline (KW-6002)
      • E2007
      • SLV-308
      • Safinamide
      • V1512
      • Pimavanserin (ACP-103)
    • Product launches in Japan
      • Comtan (entacapone)
      • Neupro (rotigotine)
      • Istradefylline (KW-6002)
    • Additional indications
      • Neupro indication for late-stage PD
    • Patent expiries
      • Requip (ropinirole)
      • Mirapex (pramipexole)
      • Comtan (entacapone)
      • Azilect
  • Data definitions, limitations and assumptions
    • Standard Units
    • Japanese market data
    • Derivation of sales forecasts and pricing trends
  • Forecast methodology
• CHAPTER 5 PIPELINE OVERVIEW - R&D DYNAMICS AND APPROACH
  • Pipeline overview
  • Classification of pipeline products
    • Dopaminergics
    • Dopamine agonists
    • Catechol-O-methyltransferase inhibitors
    • Monoamine oxidase inhibitors
    • A2a receptor antagonists
    • Drugs with neuroprotective potential
      • Modulation of the glutaminergic pathway is a promising neuroprotective strategy
      • Other neuroprotective strategies in the current pipeline
    • Other drug classes in the current pipeline
  • Clinical trial design in PD
  • Clinical trial endpoints in PD
    • Decreased cumulative OFF time is the key to approval
    • Unified PD Rating Scale
      • 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
    • The Hoehn and Yahr staging is widely used in clinical trials
• CHAPTER 6 LATE-STAGE DRUG ANALYSIS & FORECASTS
  • Late-stage pipeline overview
  • Dopaminergic class pipeline drugs
    • Pipeline summary
    • V1512 (melevodopa-carbidopa)
      • Drug overview: Levodopa methyl ester and carbidopa
      • Forecasts to 2016
      • Marketing factors
      • Patient potential
      • Satisfaction of unmet needs
      • Clinical trials
  • Dopamine agonist class pipeline drugs
    • Pipeline summary
    • Requip Modutab/XL 24-hour
      • Drug overview: extended release version of Requip
      • Forecasts to 2016
      • Marketing factors
      • Patient potential
      • Satisfaction of unmet needs
      • Clinical trial data
      • Ongoing clinical trials
    • SLV-308
      • Drug overview
      • Forecasts to 2016
      • Marketing factors
      • Patient potential
      • Satisfaction of unmet needs
      • Clinical trial data
      • Ongoing trials
    • Other drugs in the dopamine agonist class
      • Lisuride (TTS/Sub Q)
      • Rotigotine nasal spray
      • Apomorphine nasal powder
      • Apomorphine Aspirair inhaler
  • Catechol-O-methyltransferase inhibitors
    • Pipeline summary
    • BIA-3-202
  • MAOI class pipeline drugs
    • Pipeline summary
    • Safinamide (NW-1015)
      • Drug overview
      • Forecasts to 2016
      • Marketing factors
      • Patient potential
      • Satisfaction of unmet needs
      • Clinical trials data
  • Adenosine A2A receptor antagonist class pipeline drugs
    • Pipeline summary
    • Istradefylline (KW-6002)
      • Drug overview-novel mechanism of action
      • Forecasts to 2016
      • Marketing factors
      • Patient potential
      • Satisfaction of unmet needs
      • Clinical trial data
      • Further studies
    • Other drugs in the adenosine A2a receptor antagonist class
      • Fipamezole (JP-1730)
      • SCH-420814 analog
      • BIIB-014/V2006
  • Drugs with neuroprotective potential
    • Pipeline summary
    • E2007
      • Drug overview
      • Forecasts to 2016
      • Marketing factors
      • Patient potential
      • Satisfaction of unmet needs
      • Clinical trial data
      • Ongoing Phase III trials
    • PD-02 (creatine)
      • Phase II clinical trials
    • Paliroden (SR-57667)
      • Ongoing clinical trials
      • Datamonitor comments
    • GM1 ganglioside
      • Drug overview
      • Clinical trials
      • Phase II study of GM1 ganglioside in mild to moderate PD
      • NCT00037830-Phase II study of GM1 ganglioside in mild to moderate PD
    • Kinampa (talampanel)
      • Drug overview
      • Clinical trials
    • FP-0011
      • Drug overview
      • Clinical trials
    • Cereact Capsule (ONO-2506PO)
  • Others drug classes in the current pipeline
    • Pipeline summary
    • Pimavanserin (ACP-103)
      • Forecasts to 2016
      • Marking factors
      • Patient potential
      • Satisfaction of unmet needs
      • Clinical trials
      • Ongoing clinical trials
    • Zonegran (zonisamide)
      • Drug overview
      • Clinical trials
    • Keppra (levetiracetam)
      • Clinical trials
      • Ongoing studies
      • Patient potential and marketing factors
• CHAPTER 7 CELL/GENE THERAPIES AND EARLY-STAGE PROJECTS
  • Cell/gene therapy
    • Pipeline summary
      • The role of cell and gene therapies in Parkinson' s disease
    • Spheramine (RPE cell therapy)
      • Overview
      • Clinical trials
      • Ongoing trials-STEPS Phase II double-blind study
    • AV-201
      • Overview
      • Clinical trials
    • CERE-120
      • Overview
      • Preclinical animal studies
      • Phase I trial-proof of concept in humans
      • Ongoing Phase II clinical trial
    • ProSavin
      • Overview-only in preclinical development but a promising candidate
      • Trials due to start in Q4 2007
  • Key Phase I compounds in PD
    • Phase I overview
• BIBLIOGRAPHY
  • Journal papers
  • Websites
• APPENDIX
  • Report methodology
    • Contributing experts
  • About Datamonitor
    • About Datamonitor Healthcare
    • About the CNS analysis team
    • Disclaimer
  • List of Tables
    • Table 1: Prevalence of PD across the seven major markets, 2007
    • Table 2: Mirapex patent expiry dates, US and 5EU
    • Table 3: Study design-assessment of pramipexole in early PD
    • Table 4: Study design for the assessment of pramipexole in early PD
    • Table 5: Adverse events occurring in >5% of early PD patients on pramipexole as a monotherapy
    • Table 6: Study design for pramipexole in advanced PD with levodopa
    • Table 7: Key results from study of pramipexole versus placebo in advanced PD with levodopa
    • Table 8: Adverse events occurring in >5% of advanced PD patients treated with pramipexole in addition to levodopa
    • Table 9: Number of adverse events occurring with Neupro and placebo
    • Table 10: Study design in the assessment of rotigotine CDS in early PD
    • Table 11: Key results from large-scale studies of rotigotine CDS in treating patients with early PD
    • Table 12: Commonly occurring adverse events that were more frequent in those treated with rotigotine than placebo
    • Table 13: Results from the North American study (SEESAW) of entacapone in patients experiencing ON and OFF periods despite optimized levodopa therapy
    • Table 14: Results from the Nordic study (NOMECOMT) of entacapone in patients experiencing ON and OFF periods despite optimized levodopa therapy
    • Table 15: Results from the German-Austrian study of entacapone in patients taking levodopa-DDI and experiencing "wearing off"
    • Table 16: Adverse events occurring in ≥5% of entacapone patients
    • Table 17: Forecast launch dates in the US and 5EU
    • Table 18: Forecast launch dates in Japan
    • Table 19: Pivotal patent expires for key marketed drugs in the US and 5EU
    • Table 20: Unified PD Rating Scale-cognition, behavior and mood
    • Table 21: The five stages of PD according to the Hoehn and Yahr scale
    • Table 22: Key pipeline drugs in late-stage development for PD, 2007
    • Table 23: Late-stage development pipeline, dopaminergic class, 2006
    • Table 24: Key factors impacting sales of V1512, 2007-16
    • Table 25: Phase II studies of V1512 conducted by Chiesi
    • Table 26: Phase III studies of V1512 conducted by Chiesi
    • Table 27: Late-stage development pipeline, dopamine agonist class, 2007
    • Table 28: Key factors impacting sales of Requip Modutab, 2007-16
    • Table 29: Key factors impacting sales of SLV-308, 2007-16
    • Table 30: Late-stage development pipeline, COMT class, 2007
    • Table 31: Late-stage development pipeline, MAOI class, 2007
    • Table 32: Key factors impacting the sales of safinamide, 2007-16
    • Table 33: Late-stage development pipeline, adenosine A2a receptor antagonist class, 2007
    • Table 34: Factors impacting sales of istradefylline, 2007-16
    • Table 35: Late-stage development pipeline, neuroprotective potential class, 2007
    • Table 36: Factors impacting on the sales of E2007, 2007-16
    • Table 37: Change in UPDRS score from baseline to 12 months or the need for symptomatic therapy (whichever first)
    • Table 38: Late-stage development pipeline, others class, 2007
    • Table 39: Factors impacting sales of pimavanserin, 2007-16
    • Table 40: Phase II trial results for pimavanserin
    • Table 41: Key cell/gene therapies in development for PD, 2007
    • Table 42: Projects in Phase I development for PD, 2006
    • Table 43: Datamonitor drug assessment parameters
  • List of Figures
    • Figure 1: Drug assessment summary overview of key marketed and pipeline Parkinson' s disease drugs, 2007
    • Figure 2: Historical (2003-06) and forecast (2007-16) PD sales revenue for key marketed and pipeline drugs across the 7MM
    • Figure 3: Aging population across the seven major markets (%), 2000-2050
    • Figure 4: Key unmet needs in PD, 2007
    • Figure 5: Levodopa dose required to relieve symptoms compared to dose required to induce dyskinesias
    • Figure 6: Pharmacological treatment algorithm for PD
    • Figure 7: Mechanism of action of levodopa therapy
    • Figure 8: Mechanism of action of AADC inhibitors (DDIs)
    • Figure 9: Mechanism of action of COMT inhibitor (entacapone)
    • Figure 10: Mechanism of action of MAO-B inhibitors
    • Figure 11: PD-specific sales revenue, 7MM, 2003-06
    • Figure 12: PD-specific IMS standard unit volume, 7MM, 2003-06
    • Figure 13: PD-specific sales revenue by region and country, 2006
    • Figure 14: PD total market value in the US, Japan and 5EU, 2003-16
    • Figure 15: Current marketed drugs-clinical and commercial assessment
    • Figure 16: Sales (2006) and sales growth (2005-06) for key PD products
    • Figure 17: Mirapex SWOT analysis, 2007
    • Figure 18: Branded Mirapex PD sales revenue, 7MM, 2003-16
    • Figure 19: Key results from six month trial of pramipexole monotherapy versus placebo in treating patients with early PD
    • Figure 20: Key results from mixed-dose study of pramipexole monotherapy versus placebo in treating patients with early PD
    • Figure 21: Neupro SWOT analysis, 2007
    • Figure 22: Neupro PD-specific sales revenue, 7MM, 2003-16
    • Figure 23: Sales revenue generated by Neupro, Q1 2006-Q1 2007.
    • Figure 24: Diagrammatic representation of Neupro' s mode of action
    • Figure 25: Change in UPDRS-II-III scores compared to placebo for groups taking 2-8mg/24hr of rotigotine
    • Figure 26: UPDRS part II and III scores with Neupro versus placebo
    • Figure 27: Study SP512 results-comparison of rotigotine versus placebo in early PD over 24 weeks maintenance
    • Figure 28: Study SP513 results-comparison of rotigotine versus ropinirole and placebo in early PD over 24-week maintenance period
    • Figure 29: Comtan SWOT analysis, 2007
    • Figure 30: Branded Comtan PD sales revenue, 7MM, 2003-16
    • Figure 31: Key results from the North American study (SEESAW) of entacapone in patients experiencing ON and OFF periods despite optimized levodopa therapy
    • Figure 32: Key results from the Nordic study (NOMECOMT) of entacapone in patients experiencing ON and OFF periods despite optimized levodopa therapy
    • Figure 33: Stalevo SWOT analysis, 2007
    • Figure 34: Stalevo PD sales revenue, 7MM, 2003-16
    • Figure 35: Selegiline formulations sales revenue, 7MM, 2003-06
    • Figure 36: Total selegiline PD sales, 7MM, 2003-16
    • Figure 37: Azilect SWOT analysis, 2007
    • Figure 38: Azilect PD sales revenue, 7MM, 2003-16
    • Figure 39: TEMPO study-change in UPDRS score with 1mg/day rasagiline versus placebo over six months
    • Figure 40: TEMPO study-change in UPDRS score with rasagiline versus placebo over 12 months
    • Figure 41: Change over 18 weeks in the LARGO study of rasagiline as an adjunct to treatment in patients with moderate-to-advanced PD
    • Figure 42: Change in daily ON time without troublesome dyskinesia over 18 weeks in the LARGO study of rasagiline as an adjunct to treatment in patients with moderate-to-advanced PD
    • Figure 43: Change in daily ON time with troublesome dyskinesia over 18 weeks in the LARGO study of rasagiline as an adjunct to treatment in patients with moderate-to-advanced PD
    • Figure 44: Change in daily OFF time over 26 weeks in the PRESTO study of rasagiline as an adjunct to treatment in moderate-to-advanced PD patients with motor complications
    • Figure 45: Impact of each key event on the PD market across the seven major markets, 2007-2016
    • Figure 46: Late-stage pipeline overview, 2007
    • Figure 47: PD-specific sales revenue of melevodopa formulations in Italy, 2003-06
    • Figure 48: Forecast PD sales for V1512, 7MM, 2007-16
    • Figure 49: Drug assessment summary for V1512, 2007
    • Figure 50: Vernalis' s potential PD portfolio
    • Figure 51: Forecast PD sales for Requip Modutab across the seven major markets, 2007-16
    • Figure 52: Drug assessment summary for Requip Modutab, 2007
    • Figure 53: Forecast PD sales for SLV-308, 7MM, 2007-16
    • Figure 54: Drug assessment summary for SLV-308, 2007
    • Figure 55: SLV-308 Phase II data
    • Figure 56: Forecast PD sales for safinamide, 7MM, 20-2016
    • Figure 57: Drug assessment summary for safinamide, 2007
    • Figure 58: Forecast PD sales for istradefylline, 7MM, 2007-16
    • Figure 59: Drug assessment summary for istradefylline, 2007
    • Figure 60: Forecast PD sales for E2007, 7MM, 2007-16
    • Figure 61: Drug assessment summary for E2007, 2007
    • Figure 62: E2007 proof-of-concept Phase IIb trial results
    • Figure 63: Forecast PD sales for pimavanserin, 7MM, 2007-16
    • Figure 64: Drug assessment summary for pimavanserin, 2007
    • Figure 65: AADC involvement in the metabolism of levodopa
    • Figure 66: Diagrammatic representation of the proposed mode of action of CERE-120 treatment
    • Figure 67: Increased expression of the neurotrophic factor neurturin in rats following CERE-120 treatment
    • Figure 68: 18F-Dopa PET scans of treated and untreated hemispheres of monkey brains
    • Figure 69: PD symptom improvement in MPTP lesioned monkeys
    • Figure 70: Diagrammatic representation of the mode of action of ProSavin
    • Figure 71: Results showing the effects of ProSavin in MPTP-treated primates