parkinson's disease therapeutics market to 2019 · parkinson's disease therapeutics...

Parkinson's Disease Therapeutics Market to 2019 Pipeline Shows Shift Towards Long Term Disease Management

GBI Research Report Guidance

© GBI Research. This is a licensed product and is not to be photocopied GBIHC313MR / Published DEC 2013

GBI Research Report Guidance

The report begins with an executive summary detailing the key points that are driving the PD market.

Chapter two provides an introduction to PD, detailing the etiology, epidemiology, diagnostic techniques, disease staging and typical prognoses for patients. An analysis of current treatment algorithms and options is also included.

Chapter three offers detailed analysis of the 18 drugs currently marketed for this indication. Detailing the key characteristics of these drugs, including: safety and efficacy, clinical trial outcomes, tolerability, dosing, administration, historical sales, prices and overall competitive strength. These products are also compared in a comprehensive heat map.

Chapter four provides detailed analysis of the pipeline for PD, by stage of development, molecule type, program type, mechanism of action and molecular target. It also analyses recent clinical trials in this indication by enrollment, duration and failure rate. Finally, promising late-stage pipeline molecules are analyzed and assessed in terms of their potential competitive strength.

Chapter five supplies market forecasts for the PD market, including: epidemiology, treatment usage patterns, pricing and market size for the 2012–2019 period. Eight major markets (the US, Canada, Germany, the UK, France, Italy, Spain and Japan) are covered and data is presented on a country-by-country level, with further analysis of key market drivers and barriers.

Chapter six describes the major deals that have taken place in the global PD market in recent years. This coverage analyzes licensing and co-development agreements, segmented by stage of development, year, molecule type, mechanism of action and value. Network graphs for these deals are also included, organized by location of company headquarters.


Executive Summary

Executive Summary

Impact of Patent Expiration Unlikely to Be Diminished by New Market Entrants

Due to upcoming patent expirations for four high-profile drugs, the global Parkinson’s Disease (PD) market is expected to decline over the forecast period from $XX billion in 2012 to $XX billion in 2019. However, due to the time delay in drug submission in Canada and Japan, the impact of patent expirations will not be as immediate as in the US and European Union (EU). These patent expirations include Azilect (rasagiline mesylate), Stalevo (levodopa, carbidopa, entacapone) and Comtan (entacapone). Generic alternatives for these drugs have already been approved, which will result in future generic competition over the forecast period. In addition, the impact of the patent expiration of Mirapex (pramipexole dihydrochloride) and Exelon (rivastigmine tartrate) in 2010 and 2012 will continue to halt the market growth over the forecast period.

Although the approval of a few market entrants is anticipated over the forecast period, this is not expected to be significant enough to diminish the impact of generic erosion. As new entrants will be competing against cheaper generic products, they are not expected to demand a premium price. An example is Rytary (carbidopa, levodopa) which was developed by Impax Laboratories. The extended-release formulation of levodopa/carbidopa will face intense competition against generic alternatives to Sinemet if approved.

Shifting Focus of Pipeline to Long-Term Management of Parkinson’s Disease

One of the limitations of existing dopaminergic therapies is the motor complications that arise after several years of treatment. Levodopa-associated motor complications such as the wearing-off phenomenon and dyskinesia can profoundly affect the quality of life in patients with PD. Around XX% of patients develop motor complications after five years of levodopa treatment (Lang and Lozano, 1998). However, current treatment options for these complications remain very limited.

As reflected in the pipeline, treatments focusing on improving levodopa-associated complications have received a considerable amount of attention in recent years. Key pipeline candidates have been under investigation for treating wearing-off and Levodopa-Induced Dyskinesia (LID). They include tozadenant, mavoglurant and dipraglurant, which are developed by Biotie Therapies, Novartis and Addex Therapeutics, respectively. In particular, mavoglurant and dipraglurant have demonstrated promising antidyskinesia effects in Phase II. These new developments may potentially bring changes in the future treatment algorithm as side effects of dopaminergic therapies become more manageable.

High Number of Neuroprotective Targets in Early Pipeline

With existing products focusing on symptomatic relief, a disease-modifying treatment remains an urgent unmet need in PD. The current PD pipeline is made up of XX% neuroprotective targets. The majority, XX%, are currently in discovery and Preclinical development, while the remaining molecules are distributed in Phase I and II. These targets represent innovation in the pipeline and could become an effective disease-modifying treatment in the future.

However, that development of such treatment remains challenging, with several obstacles yet to be overcome. The absence of neuroprotective candidates in the late pipeline has been a recurring issue. Of all the challenges, the most urgent is the need for a reliable biomarker for PD that can accelerate the development of treatment.


Table of Contents

1 Table of Contents

1 Table of Contents ................................................................................................................................. 4 1.1 List of Tables ............................................................................................................................. 6 1.2 List of Figures............................................................................................................................ 6

2 Introduction......................................................................................................................................... 8 2.1 Overview .................................................................................................................................. 8 2.2 Epidemiology ............................................................................................................................ 9 2.3 Etiology .................................................................................................................................... 9

2.3.1 Loss of Dopaminergic Neurons ........................................................................................... 9 2.3.2 Genetic Factors ................................................................................................................. 9 2.3.3 Exposure to Environmental Toxins ....................................................................................10

2.4 Pathophysiology ......................................................................................................................10 2.4.1 Pathophysiological Changes in Basal Ganglia in Parkinson’s Disease..................................12 2.4.2 Pathophysiological Changes Involved in the Rise of Motor Complications in Parkinson’s

Disease ............................................................................................................................12 2.5 Symptoms ...............................................................................................................................13 2.6 Co-morbidities and Complications ............................................................................................14 2.7 Diagnosis .................................................................................................................................14

2.7.1 Classification ....................................................................................................................15 2.8 Prognosis and Disease Staging ..................................................................................................19 2.9 Treatment Options ..................................................................................................................20

2.9.1 Pharmacological Treatment .............................................................................................20 2.9.2 Non-pharmacological Treatments.....................................................................................22 2.9.3 Treatment Algorithm........................................................................................................23

3 Marketed Products .............................................................................................................................27 3.1 Therapeutic Landscape ............................................................................................................28

3.1.1 Dopamine Replacement Therapies ....................................................................................28 3.1.2 MAO-B inhibitors .............................................................................................................32 3.1.3 Dopamine Agonists ..........................................................................................................34 3.1.4 COMT Inhibitors ...............................................................................................................44 3.1.5 Nouriast (istradefylline) – Kyowa Hakko Kirin ....................................................................46 3.1.6 Exelon (rivastigmine tartrate) – Novartis AG .....................................................................46 3.1.7 Symmetrel (amantadine hydrochloride) – Alliance Pharma Plc...........................................48 3.1.8 Other drugs targeting non-motor symptoms of PD ............................................................49

3.2 Comparative Efficacy and Safety...............................................................................................50 3.3 Unmet Need ............................................................................................................................54

4 Pipeline for Parkinson’s Disease ..........................................................................................................55 4.1 Overall Pipeline........................................................................................................................55 4.2 Molecular Targets in Parkinson’s Disease Pipeline ....................................................................57 4.3 Clinical Trials ............................................................................................................................60

4.3.1 Failure Rate of Developmental Pipeline .............................................................................60 4.3.2 Clinical Trial Sizes .............................................................................................................63 4.3.3 Clinical Trial Duration .......................................................................................................64 4.3.4 Summary of Clinical Trial Cost and Risk Analyses ...............................................................66

4.4 Promising Candidates in Pipeline ..............................................................................................67 4.4.1 Rytary (carbidopa, levodopa) – Impax Laboratories, Inc.....................................................67 4.4.2 Safinamide – Newron Pharmaceuticals S.p.A ....................................................................67 4.4.3 Pimavanserin – Acadia Pharmaceuticals Inc. .....................................................................68 4.4.4 Tozadenant – Biotie Therapies ..........................................................................................69 4.4.5 Mavoglurant – Novartis AG ..............................................................................................69 4.4.6 Dipraglurant – Addex Therapeutics ...................................................................................70


Table of Contents

4.5 Heat Map of Safety and Efficacy for Parkinson’s Disease Pipeline and Marketed Products .........71 5 Market Forecast to 2019 .....................................................................................................................75

5.1 Geographical Markets ..............................................................................................................75 5.1.1 Global Market ..................................................................................................................76 5.1.2 North America .................................................................................................................78 5.1.3 Top Five Countries of Europe ............................................................................................81 5.1.4 Japan ...............................................................................................................................85

5.2 Drivers and Barriers .................................................................................................................87 5.2.1 Drivers .............................................................................................................................87 5.2.2 Barriers ............................................................................................................................88

6 Deals and Strategic Consolidations ......................................................................................................90 6.1 Major Co-development Deals ...................................................................................................90

6.1.1 Newron Pharmaceuticals S.p.A. Enter Agreement with Zambon Company S.p.A. ................92 6.1.2 QR Pharma, Inc. Enter Research Agreement with Massachusetts General Hospital.............93 6.1.3 Ceregene, Inc. Enter Agreement with Genzyme Corporation ..............................................93

6.2 Major Licensing Deals ..............................................................................................................93 6.2.1 Biotie Therapies Corp. Enter Worldwide Agreement with UCB Group .................................96 6.2.2 Ono Pharmaceutical Co., Ltd. Enter Agreement with Bial - Portela & Ca, S.A ......................96 6.2.3 Domain Therapeutics S.A. Enter Agreement with Prexton Therapeutics .............................97 6.2.4 Newron Pharmaceuticals S.p.A. Enter Agreement with Zambon Company S.p.A. ................97 6.2.5 Oncodesign SA Enter Agreement with Ipsen S.A. ...............................................................97 6.2.6 Cephalon, Inc. Enter Licensing Agreement with Mesoblast Limited.....................................97 6.2.7 Shire Pharmaceutical Group Plc Enter Agreement with Heptares Therapeutics Ltd. ............98

7 Appendix ............................................................................................................................................99 7.1 All Pipeline Products, by Phase .................................................................................................99 7.2 Sources.................................................................................................................................. 109 7.3 Market Definition .................................................................................................................. 119 7.4 Abbreviations ........................................................................................................................ 119 7.5 Research Methodology .......................................................................................................... 120

7.5.1 Coverage ....................................................................................................................... 120 7.5.2 Secondary Research ....................................................................................................... 121

7.6 Therapeutic Landscape .......................................................................................................... 121 7.7 Epidemiology-Based Forecasting ............................................................................................ 121 7.8 Market Size by Geography ..................................................................................................... 122 7.9 Geographical Landscape ........................................................................................................ 123 7.10 Pipeline Analysis .................................................................................................................... 124 7.11 Competitive Landscape .......................................................................................................... 124

7.11.1 Expert Panel Validation .................................................................................................. 124 7.12 Contact Us ............................................................................................................................. 124 7.13 Disclaimer.............................................................................................................................. 124


Table of Contents

1.1 List of Tables

Table 1: Definition of the Stages of Disability in Hoehn and Yahr Scale ..................................................15 Table 2: Evaluation of Disability by UPDRS ............................................................................................17 Table 3: Definition of the Stages of Disability in Hoehn and Yahr Scale ..................................................99 Table 4: Evaluation of Disability by UPDRS ............................................................................................99 Table 5: All Pipeline Products by Phase, Discovery .............................................................................. 100 Table 6: All Pipeline Products by Phase, Preclinical .............................................................................. 101 Table 7: All Pipeline Products by Phase, IND/CTA Filed and Phase I ...................................................... 104 Table 8: All Pipeline Products by Phase, Phase II ................................................................................. 104 Table 9: All Pipeline Products by Phase, Phase III and Pre-registration ................................................. 105 Table 10: Parkinson’s Disease, Global, Market Forecast, 2012-2019 ...................................................... 105 Table 11: Parkinson’s Disease, US, Market Forecast, 2012-2019 ............................................................ 105 Table 12: Parkinson’s Disease, Canada, Market Forecast, 2012-2019 ..................................................... 106 Table 13: Parkinson’s Disease, UK, Market Forecast, 2012-2019 ............................................................ 106 Table 14: Parkinson’s Disease, France, Market Forecast, 2012-2019 ...................................................... 106 Table 15: Parkinson’s Disease, Germany, Market Forecast, 2012-2019 .................................................. 107 Table 16: Parkinson’s Disease, Italy, Market Forecast, 2012-201 ........................................................... 107 Table 17: Parkinson’s Disease, Spain, Market Forecast, 2012-2019 ........................................................ 107 Table 18: Parkinson’s Disease, Japan, Market Forecast, 2012-2019 ....................................................... 108

1.2 List of Figures

Figure 1: Indirect and Direct Pathway in Basal Ganglia ...........................................................................11 Figure 2: Treatment Algorithm of Parkinson’s Disease ............................................................................24 Figure 3: Treatment Algorithm of Advanced Parkinson’s Disease ............................................................25 Figure 4: Parkinson’s Disease Market, Global, Annual Sales of Madopar ($m), 2008–2012 ......................29 Figure 5: Parkinson’s Disease Market, Global, Annual Sales of Stalevo and Comtan ($m), 2005–2012 ......30 Figure 6: Parkinson’s Disease Market, Global, Annual Sales of Azilect ($m), 2006–2012 ..........................33 Figure 7: Parkinson’s Disease Market, Global, Annual Sales of Requip ($m), 2001–2012 ..........................35 Figure 8: Parkinson’s Disease Market, Global, Annual Sales of Mirapex ($m), 2005–2010 ........................37 Figure 9: Parkinson’s Disease Market, Global, Annual Sales of Neupro ($m), 2007–2012 .........................39 Figure 10: Parkinson’s Disease Market, Global, Annual Sales of Apokyn ($m), 2006–2011 .........................41 Figure 11: Parkinson’s Disease Market, Global, Annual Sales of Permax ($m), 2009–2012 .........................42 Figure 12: Parkinson’s Disease Market, Global, Annual Sales of Exelon ($m), 2002–2012 ..........................47 Figure 13: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products, 2012–2019......51 Figure 14: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products, 2012–2019......52 Figure 15: Pipeline for Parkinson’s Disease, Global, 2012 .........................................................................56 Figure 16: Pipeline for Parkinson’s Disease, Global, 2012 .........................................................................57 Figure 17: Pipeline for Parkinson’s Disease, Global, Clinical Trial Failure Rates (%), 2006–2012..................61 Figure 18: Pipeline for Parkinson’s Disease, Global, Clinical Trial Sizes (Participants), 2006–2012 ..............63 Figure 19: Pipeline for Parkinson’s Disease, Global, Clinical Trial Duration (Months), 2006–2012...............65 Figure 20: Pipeline for Parkinson’s Disease, Global, Mean Number of Clinical Trials Per Pipeline Drug, 2006–

2012 .......................................................................................................................................66 Figure 21: Parkinson’s Disease Market, Global, Efficacy Heat Map for Pipeline Products, 2012–2019 ........72 Figure 22: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products, 2012–2019......73 Figure 23: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products, 2012–2019......74 Figure 24: Parkinson’s Disease Market, Global, Annual Sales ($bn), 2012–2019 ........................................76 Figure 25: Parkinson’s Disease Market, North America, Treatment Patterns, 2012–2019 ..........................78 Figure 26: Parkinson’s Disease Market, North America, Annual Cost of Therapy ($), 2012–2019 ...............79 Figure 27: Parkinson’s Disease Market, North America, Market Size ($m), 2012–2019 ..............................80 Figure 28: Parkinson’s Disease Market, Top Five EU Countries, Treatment Patterns, 2012–2019 ...............82 Figure 29: Parkinson’s Disease Market, Top Five EU Countries, Annual Cost of Therapy ($), 2012–2019 ...83 Figure 30: Parkinson’s Disease Market, Top Five EU Countries, Market Size ($m), 2012–2019 ...................84 Figure 31: Parkinson’s Disease Market, Japan, Treatment Patterns and Annual Cost of Therapy ($), 2012–

2019 .......................................................................................................................................85 Figure 32: Parkinson’s Disease Market, Japan, Market Size ($m), 2012–2019 ............................................86


Table of Contents

Figure 33: Parkinson’s Disease Market, Global, Co-Development Deals, 2006–2013..................................91 Figure 34: Parkinson’s Disease Market, Global, Co-Development Deals, 2006–2013..................................92 Figure 35: Parkinson’s Disease Market, Global, Licensing Deals, 2006–2013 .............................................94 Figure 36: Parkinson’s Disease Market, Global, Licensing Deals, 2006–2013 .............................................95 Figure 37: Parkinson’s Disease Market, Global, Breakdown of Licensing Deals in Other Non-dopaminergic

Neuromodulatory Targets, 2006–2013 ....................................................................................96 Figure 38: GBI Research Market Forecasting Model ............................................................................... 123


Introduction

2 Introduction

2.1 Overview

Parkinson’s Disease (PD) is a progressive neurodegenerative disease caused by the loss of dopamine-producing neurons in the substantia nigra. It is estimated that XX million people suffer from PD worldwide (Parkinson’s UK, 2013). PD affects both men and women, with the risk of developing the disease increasing in the age range of XX–XX (Driver and Kurth, 2009). People suffering from PD experience difficulties in conducting daily activities as the disease affects body movement and control. Major motor symptoms include tremors, bradykinesia and impaired balance. As the disease progresses, non-motor symptoms such as depression and sleeping disorders may also develop.

With increasing life expectancies and aging populations, the prevalence of PD is expected to rise. The current market constitutes an abundance of symptomatic treatments targeting functional impairment in PD, thus significantly improving the quality of life of patients. The most effective drug is levodopa, which has remained the standard care of treatment in PD for almost XX years. There is a huge unmet need for disease-modifying treatments that slow progression or provide neuroprotective characteristics. Some of the major obstacles to developing new disease-modifying therapeutics are an incomplete understanding of the molecular mechanisms involved in PD and the difficulty in modulating cellular processes and/or signaling pathways for disease modification without compromising essential and finely tuned homeostatic functions in the human brain. In addition, an absence of biomarkers to test potentially neuroprotective intervention increases the barrier of developing treatments for PD (Olanow, et al., 2008). A validated biomarker will allow the detection of neuroprotection in clinical trials and help improve trial design by reducing recruitment sizes and duration, thus accelerating the development of disease-modifying treatment.

With the presence of these challenges in the market, the focus of innovation is turned to reformulations and targeting side effects of levodopa treatment, as reflected in the late-stage PD pipeline. One promising development is the new treatment addressing cognitive impairment of PD, which is one of the unmet needs in the market. In the foreseeable future, symptomatic treatments for both motor and non-motor symptoms are likely to remain the dominant player in the market.

Pipeline for Parkinson’s Disease

© GBI Research. This is a licensed product and is not to be photocopied GBIHC305MR / Published SEP 2013 Page 55

4 Pipeline for Parkinson’s Disease

4.1 Overall Pipeline

With the current marketed drugs focusing primarily on symptomatic relief, PD remains an incurable disease with a huge unmet need for disease-modifying therapies. However, with the lack of clear established clinical trial methodologies, replication of the benefits demonstrated by neuroprotective agents in laboratory to human trials have proved challenging. More importantly, due to an incomplete understanding of the underlying mechanisms that cause the disease, a viable therapeutic target to halt or slow disease progression is currently not in sight, which limits the effectiveness of current product development programs.

Another major unmet need is the treatment of cognitive impairment. Patients with PD are currently prescribed atypical antipsychotic medications, which have serious side effects, and there is a clear lack of treatment choice for PD patients with cognitive impairment. The current pipeline consists of a promising drug, pimavanserin, which addresses this unmet need.

The current pipeline for PD is considered to be highly active. In total, XX pipeline products are undergoing development, with XX% in the Preclinical stage, XX% in Phase XX, XX% in Phase XX and XX% in Phase XX. Three drug candidates are currently in pre-registration. Rytary is an investigational extended-release formulation of levodopa/carbidopa. A complete response letter was issued by the FDA, stating that a re-inspection of its manufacturing plant would be required before drug approval. Nouriast, which was approved in Japan in 2013, is still awaiting FDA approval. In addition, a total of XX products have been discontinued or are not in the process of active development. Although a high proportion of novel products are present in the discovery and Preclinical stages, data show a lack of novel compounds in mid-to-late clinical trial stages. Generics and repositioned product compounds together account for almost half of the products in Phase XX. One of the pre-registered candidates is also a generic product containing a marketed API, but with different delivery method.

[…] Sinemet will face competition against Rytary, an extended-release formulation of levodopa and carbidopa which is currently under review by FDA



Figure 15: Pipeline for Parkinson’s Disease, Global, 2012

A BPD Pipeline by Stage

PD Pipeline by Programme Type by Stage

PD Pipeline by Molecule Type by Stage

C

PD Pipeline by Molecule Type

D

Discovery PreclinicalIND/CTA-filed Phase IPhase II Phase IIIPre-registration

Total=XX

Small molecule Biologics

Cell therapy/gene therapy Unknown

Total=XX

Novel Repositioned Generics Small molecule Biologics

Cell therapy/gene Therapy Unknown

Source: GBI Research, Proprietary Pipeline Products Database

The pipeline is made up of small molecules, biologics, and cell and gene-therapy compounds. Small molecules, which represent a total of XX% of the PD pipeline, constitute a significant proportion in each clinical trial phase. Biologics, cell therapy and gene therapy make up XX% and XX% of the pipeline, respectively. Biologics, and cell and gene therapies are found in early-to-mid clinical trial stages, but are absent in Phase XX. The absence of biologics drug candidates in late clinical trial stages is expected, since the majority of the large molecules are unable to cross the BBB.

The PD pipeline continues to be dominated by symptomatic treatments. The late-stage clinical trials relate to drug candidates that show effectiveness in relieving motor symptoms. Safinamide, one of the most promising candidates in the pipeline, showed improvements in motor function with dual mechanism of action. Another promising candidate that could have a huge impact on the PD market is pimavanserin. If it is approved, it will address one of the unmet needs for a treatment of cognitive impairment in PD. However, there were also several failures in the late-stage clinical trials for PD treatment. Preladenant, an adenosine A2A antagonist, was discontinued by Merck in Phase III due to the lack of efficacy. High unmet need remains in the market, as there are no drug candidates in late-stage development that provide a cure or successfully slow the progression of disease.

Small molecules, which represent a total of XX% of the PD pipeline, constitute a significant proportion in each clinical trial phase



4.2 Molecular Targets in Parkinson’s Disease Pipeline

There are a wide range of molecular targets present in the pipeline that can be divided into three major groups: dopaminergic; other non-dopaminergic neuromodulatory; and neuroprotective targets. Across all phases, the pipeline consists XX%, XX% and XX% of each group respectively.

Figure 16: Pipeline for Parkinson’s Disease, Global, 2012

PD Pipeline by Targets PD Pipeline by Targets by StageA B

Breakdown of Dopaminergic Target

C Breakdown of Other Non-dopaminergic Neuromodulatory Target

D

Breakdown of Neuroprotective TargetE

Dopaminergic target

Other non-dopaminergic neuromodulatory target

Neuroprotective target

Other

Unknown

Total=XX

Dopaminergic TargetOther non-dopaminergic neuromodulatory targetNeuroprotective targetOtherUnknown

Alpha-synuclein inhibitor

LRRK-2 inhibitor

GDNF, other neurotrophic factors and growth factors

Total=XX

Adenosine A2A receptor antagonistMetabotropic glutamate receptor targetMuscarinic and nicotinic acetylcholine receptorSerotonin receptor target

Total=XX

Levodopa/carbidopa formulationDopamine agonistMAO-B inhibitorCOMT inhibitor

Total=XX

Source: GBI Research, Proprietary Pipeline Products Database

Market Forecast to 2019


5.1.1 Global Market

The PD global market size for the eight key countries is expected to decline from $XX billion in 2012 to $XX billion in 2019 at a negative CAGR of XX% (Figure 24.B.). By accounting for XX% of the global PD market in 2019, the US market will remain the major global market.

Figure 24: Parkinson’s Disease Market, Global, Annual Sales ($bn), 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019

Mar

ket s

ize

($bn

)

Low variance Medium variance High variance Projected

2012 2013 2014 2015 2016 2017 2018 2019

Patie

nts

('000

)

Prevalence population Diagnosed population Treatment population

Treatment Patterns

Revenue

A

BProjected CAGR 2012–2019: -2.3% Minimum CAGR 2012–2019: -3.2%Maximum CAGR 2012–2019:-0.9%

Source: GBI Research

The market decline is mainly caused by patent expiration of several marketed products within the forecast period. Patent expiration of Azilect and Comtan in the eight key markets is expected to contribute significantly to the decrease in ACoT in certain markets. It is expected that the ACoT in Canada will be the least affected since the patent expiry of several drugs occurs towards the end of the forecast period. The decline in the PD market is also brought about by the patent expiration of the strong performing drug Stalevo in 2013 in the US and Europe. Since it will not be off-patented until 2020 in Canada, the impact is not projected within the forecast period in the Canadian market.

Appendix


7 Appendix

7.1 All Pipeline Products, by Phase

Table 3: Definition of the Stages of Disability in Hoehn and Yahr Scale

Stage I

Stage II

Stage III

Stage IV

Stage V

Source: Hoehn and Yahr, 1967

Table 4: Evaluation of Disability by UPDRS

Section Key areas of disability Items for evaluation

Part I

Part II

Part III

Appendix


Part IVa

Part IVb

Source: MDVU, 2013

Table 5: All Pipeline Products by Phase, Discovery

Product Name Company Molecule Type Mechanism of Action Stage of Development


Appendix


Table 6: All Pipeline Products by Phase, Preclinical


Appendix


Appendix


Table 7: All Pipeline Products by Phase, IND/CTA Filed and Phase I



Table 8: All Pipeline Products by Phase, Phase II



Appendix


Table 9: All Pipeline Products by Phase, Phase III and Pre-registration



Table 10: Parkinson’s Disease, Global, Market Forecast, 2012-2019 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR

Prevalence population (billions)

Treatment population (billions)

Maximum revenue ($bn)

Projected revenue ($bn)

Minimum revenue ($bn)


Table 11: Parkinson’s Disease, US, Market Forecast, 2012-2019 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR

Prevalence population (millions)

Treatment population (millions)

Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)

Maximum revenue ($bn)

Projected revenue ($bn)

Minimum revenue ($bn)


Appendix


Table 12: Parkinson’s Disease, Canada, Market Forecast, 2012-2019 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR



Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)

Maximum revenue ($m)

Projected revenue ($m)

Minimum revenue ($m)


Table 13: Parkinson’s Disease, UK, Market Forecast, 2012-2019 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR



Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)





Table 14: Parkinson’s Disease, France, Market Forecast, 2012-2019 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR



Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)





Appendix


Table 15: Parkinson’s Disease, Germany, Market Forecast, 2012-2019 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR



Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)





Table 16: Parkinson’s Disease, Italy, Market Forecast, 2012-201 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR



Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)





Table 17: Parkinson’s Disease, Spain, Market Forecast, 2012-2019 Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR



Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)





Appendix


Table 18: Parkinson’s Disease, Japan, Market Forecast, 2012-2019

Year 2012 2013 2014 2015 2016 2017 2018 2019 CAGR



Maximum ACOT ($)

Projected ACOT ($)

Minimium ACOT ($)





Appendix


7.2 Sources

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Burns RS, et al. (1983). A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proceedings of the National Academy of Sciences U S A; 80(14): 4546-4550.

Burn D, et al. (2006). Effects of Rivastigmine in Patients With and Without Visual Hallucinations in Dementia Associated With Parkinson’s Disease. Movement Disorders; 21(11): 1899-1907.

Appendix


7.3 Market Definition

The global PD Market includes the top eight markets; consisting of the US, the UK, Germany, France, Spain, Italy, Japan and Canada.

The top five European countries are the UK, Germany, France, Spain and Italy

Prevalence population: The prevalence population is the estimated number of people at any given point of time who are affected by PD.

7.4 Abbreviations

5-HT: 5-Hydroxytryptamine

AAN: American Academy of Neurology

ACoT: Annual Cost of Therapy

ADCS-ADL: Alzheimer’s Disease Cooperative Study – Activities of Daily Living

API: Active Pharmaceutical Ingredient

BBB: Blood-Brain Barrier

CAGR: Compound Annual Growth Rate

CFAST: Coalition for Accelerating Standards and Therapies

CGI: Clinical Global Impression

CGI-C: global improvement of change

CGI-S: global improvement of severity

CNS: Central Nervous System

COMT: Catechol-O-Methyl Transferase

CSF: Cerebrospinal Fluid

CTA: Clinical Trial Application

DBS: Deep Brain Stimulation

DaTscan: Dopamine Transporters scan

EFNS: European Federation of Neurological Societies

ER: Extended Release

FDA: Food and Drug Administration

GABA: Gamma-Aminobutyric Acid

GDNF: Glial Cell Derived Neurotrophic Factor

GPi: Globus Pallidus interna

GPe: Globus Pallidus externa

G-CSF: Granulocyte-Colony Stimulating Factor

IND: Investigational New Drug

IR: Immediate Release

LFADLDSL: Lang-Fahn Activities of Daily Living Dyskinesia Scale

LID: Levodopa-Induced Dyskinesia

mAIMS: Modified Abnormal Involuntary Movement Scale

mGluR5: Metabotropic Glutamate Receptor 5

Appendix


MAO-B: Monoamine Oxidase-B

MMSE: Mini Mental State Examination

MPTP: 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine

MSN: Medium Spiny Neurons

NAM: Negative Allosteric Modulator

NDA: New Drug Application

NHS: National Health Service

NICE: National Institute for Health and Care Excellence

NINDS: National Institute of Neurological Disorders and Stroke

NMDA: N-Methyl-D-Aspartate

PD: Parkinson’s Disease

PDBP: Parkinson’s Disease Biomarkers Program

PET: Positron Emission Tomography

PPMI: Parkinson’s Progression Markers Initiative

RoA: Route of Administration

SAPS: Scale for the Assessment of Positive Symptoms

SPECT: Single-Photon Emission Computed Tomography

SNc: Substantia Nigra pars compacta

SNr: Substantia Nigra pars recticulata

STN: Subthalamic Nucleus

UPDRS: Unified Parkinson Disease Rating Scale

VTA: Ventral Tegmental Area

YOPD: Young-Onset Parkinson’s Disease

7.5 Research Methodology

GBI Research’s dedicated research and analysis teams consist of experienced professionals with marketing, market research and consulting backgrounds in the pharmaceutical industry as well as advanced statistical expertise.

GBI Research adheres to the codes of practice of the Market Research Society (www.mrs.org.uk) and the Strategic and Competitive Intelligence Professionals (www.scip.org).

All GBI Research databases are continuously updated and revised.

7.5.1 Coverage

The objective of updating GBI Research coverage is to ensure that it represents the most up-to-date vision of the industry possible.

Changes to the industry taxonomy are built on the basis of extensive research of company, association and competitor sources.

Company coverage is based on three key factors: market capitalization, revenues and media attention/innovation/market potential.

An exhaustive search of 56 member exchanges is conducted and companies are prioritized on the basis of their market capitalization.

Appendix


The estimated revenues of all major companies, including private and governmental, are gathered and used to prioritize coverage.

Companies which are making the news, or which are of particular interest due to their innovative approach, are prioritized.

GBI Research aims to cover all major news events and deals in the pharmaceutical industry, updated on a daily basis.

The coverage is further streamlined and strengthened with additional inputs from GBI Research’s expert panel (see below).

7.5.2 Secondary Research

The research process begins with exhaustive secondary research on internal and external sources being carried out to source qualitative and quantitative information relating to each market.

The secondary research sources that are typically referred to include, but are not limited to:

Company websites, annual reports, financial reports, broker reports, investor presentations and US Securities and Exchanges Commission (SEC) filings

Industry trade journals, scientific journals and other technical literature

Internal and external proprietary databases

Relevant patent and regulatory databases

National government documents, statistical databases and market reports;

Procedure registries

News articles, press releases and web-casts specific to the companies operating in the market

7.6 Therapeutic Landscape

Revenues for each indication, geography-wise is arrived at by utilizing the GBI Research market forecasting model. The global revenue for each indication is the sum value of revenues of all eight regions.

The annual cost of treatment for each indication is arrived at by considering the cost of the drugs, dosage of the drugs and the duration of the therapy.

The generic share of the market for each indication is obtained by calculating the prescription share for generic drugs and the respective cost of treatment.

The treatment usage pattern which includes quantitative data on the diseased population, treatment-seeking population, diagnosed population and treated population for an indication, is arrived at by referring to various sources as mentioned below.

GBI Research uses the epidemiology-based treatment flow model to forecast market size for therapeutic indications.

7.7 Epidemiology-Based Forecasting

The forecasting model used at GBI Research makes use of epidemiology data gathered from research publications and primary interviews with physicians to represent the treatment flow patterns for individual diseases and therapies. The market for any disease segment is directly proportional to the volume of units sold and the price per unit.

Sales = Volume of units sold X Price per unit

The volume of units sold is calculated on the average dosage regimen for that disease, duration of treatment and number of patients who are prescribed drug treatment (prescription population). Prescription population is calculated as the percentage of population diagnosed with a disease (diagnosis population). The diagnosis population is the population diagnosed with a disease expressed as a percentage of the population that is seeking treatment (the treatment-seeking population). The prevalence of a disease (diseased population) is the percentage of the total population that suffers from a disease/condition.

Appendix


Data on treatment-seeking rates and diagnosis and prescription rates, if unavailable from research publications, are gathered from interviews with physicians and are used to estimate the patient volumes for the disease under consideration. Therapy uptake and compliance data are fitted in the forecasting model to account for patient switching and compliance behavior.

To account for differences in patient affordability of drugs across various geographies, macroeconomic data such as inflation and GDP and healthcare indicators such as healthcare spending, insurance coverage and average income per individual are used.

The annual cost of treatment is calculated using product purchase frequency and the average price of the therapy. Product purchase frequency is calculated from the dosage data available for the therapies and drug prices are gathered from public sources. The source for the price of drugs are RxUSA, ZenRx, the UK Prescription Cost Analysis, the British National Formulary and data from the Japan Pharmaceutical Information Center (JAPIC).

The epidemiology-based forecasting model uses a bottom-up methodology and it makes use of estimations in the absence of data from research publications. Such estimations may result in a final market value which is different from the actual value. To correct this ‘gap’ the forecasting model uses ‘triangulation’ with the help of base year sales data (from company annual reports, internal and external databases) and sales estimations.

Analogous Forecasting Methodology

Analogous forecasting methodology is used to account for the introduction of new products, patent expiries of branded products and subsequent introduction of generics. Historic data for new product launches and generics penetration are used to arrive at robust forecasts. Increase or decrease of prevalence rates, treatment seeking rate, diagnosis rate and prescription rate are fitted into the forecasting model to estimate market growth rate.

The proprietary model enables GBI Research to account for the impact of individual drivers and restraints in the growth of the market. The year of impact and the extent of impact are quantified in the forecasting model to provide close-to-accurate data sets.

7.8 Market Size by Geography

The treatment usage pattern and ACoT in each country has been factored in while deriving the individual country market size.

Appendix


Forecasting Model for Therapeutic Areas

Figure 38: GBI Research Market Forecasting Model


The above figure represents a typical forecasting model followed in GBI Research. As discussed previously, the model is built on the treatment flow patterns. The model starts with the general population, then diseased population as a percentage of the general population and then follows the treatment seeking population as a percentage of the diseased population and diagnosed population as a percentage of the treatment seeking population. Finally, the total volume of units sold is calculated by multiplying the treated population by the average dosage per year per patient.

7.9 Geographical Landscape

This report series GBI Research covers the following major developed markets: the US, Canada, the top five countries in Europe – the UK, Germany, France, Spain, Italy – and Japan. The total market size for each country is provided which is the sum value of the market sizes of all the indications for that particular country.

Appendix


7.10 Pipeline Analysis

This section provides a list of molecules at various stages in the pipeline for various indications. The list is sourced from internal database and validated for the accuracy of phase and mechanism of action at ClinicalTrials.gov and company websites. The section also includes a list of promising molecules which is narrowed down based on the results of the clinical trials at various stages and the novelty of mechanism of action. The latest press releases issued by the company and news reports are also the source of information for the status of the molecule in the pipeline.

7.11 Competitive Landscape

GBI Research aims to cover all major licensing deals and co-development deals related to the market. This section is sourced from the companies’ websites, company annual reports and internal databases

7.11.1 Expert Panel Validation

GBI Research uses a panel of experts to cross verify its databases and forecasts.

GBI Research expert panel comprises marketing managers, product specialists, international sales managers from pharmaceutical companies; academics from research universities and key opinion leaders from hospitals.

Historic data and forecasts are relayed to GBI Research’s expert panel for feedback and are adjusted in accordance with their feedback.

7.13 Disclaimer

All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, GBI Research.

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