Abstract
Overview
Introduction
The PD market is set to continue to grow over the next 7 years, reaching over $2.37 billion in 2013, a 39% increase from 2006 levels. Combinations, reformulations, and indication expansions will drive the majority of this growth, with key brands expected to be Novartis/Orion' s Stalevo, GlaxoSmithKline' s (GSK' s) Requip Modutab, and UCB-Schwarz' s Neupro.
Scope
- Analysis of patient potential, unmet needs and clinical trial design in PD
- Overview of key marketed brands, late- and early-stage pipeline drugs, and cell/gene therapies.
- Indication- and country-specific sales volume and value forecasts to 2016 of marketed brands, generics, and key late-stage pipeline drugs.
- Identification of future market events that are expected to affect PD drug revenues.
Highlights
GSK' s Requip Modutab will become the market leading PD brand in 2011. It will be intuitive for prescribers to believe that sustained activation of dopamine receptors with Requip Modutab could have a significant clinical benefit over pulsed agonism with standard drugs.
New pipeline drugs will need to be innovative to compete in an increasingly crowded market. While this is evident in Eisai' s E2007, it is lacking in Merck-Serono/Newron' s safinamide.
Early studies with cell/gene therapies show great promise for significantly slowing the progression of the disease. However, these alternative approaches will not significantly impact the sales of pharmaceuticals over the forecast period 20072016.
Reasons to Purchase
- Benchmark key late-stage PD compounds against current market leading brands.
- Assess country-specific (US, Japan, France, Germany, Italy, Spain and the UK) sales forecasts of key late-stage pipeline drugs and marketed brands.
- Understand unmet needs and opportunities in the PD market based on key opinion leader comments.
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
- Epidemiology of PD
- 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
- PD market has grown over the last four years
- Market and disease definition
- 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
- New product launches
- Data definitions, limitations and assumptions
- Standard Units
- Japanese market data
- Derivation of sales forecasts and pricing trends
- Forecast methodology
- Key events
- 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
- Pipeline summary
- Key Phase I compounds in PD
- Phase I overview
- Cell/gene therapy
- 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
- Report methodology
