US sample - MarketResearch.com: Market Research ...Neuropathic Pain - US Drug Forecast and Market Analysis to 2022 2 © GlobalData. This report is a licensed product and is not to

REFERENCE CODE GDHC239CFR | PUBLICAT ION DATE APRIL 2014

NEUROPATHIC PAIN - US DRUG FORECAST AND MARKET ANALYSIS TO

2022

Neuropathic Pain - US Drug Forecast and Market Analysis to 2022 2 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.

NEUROPATHIC PAIN - US DRUG FORECAST AND MARKET ANALYSIS TO 2022

Executive Summary

Sales for Neuropathic Pain (NP) in the US

The US NP market was valued at an estimated

$1.8 billion in 2012. GlobalData expects the market

to grow at a Compound Annual Growth Rate

(CAGR) of 2.7% to $2.3 billion by 2022.

Major drivers of the growth of the NP market

over the forecast period include:

US healthcare reform will increase patient

access to treatment and thus increase

treatment rates.

US obesity epidemic will lead to the increased

prevalence of type 2 diabetes, and

consequently, an increased prevalence of

PDN.

The increasing NP incidence due to the

growing elderly population

The approval of novel formulations and first-in-

class therapies in the pipeline for NP, which

will drive sales in this market

Major barriers to the growth of the NP market over

the forecast period include:

Launch of generic competitors to Cymbalta

sand Lidoderm in 2013, and Lyrica in 2018, will

lead to market contraction.

Medicare spending cuts will create greater

emphasis on the affordability of healthcare.

Prescription drug abuse, particularly with

opioids, is leading to stricter regulations

governing their use.

Figure below illustrates the US NP sales during the

forecast period.

Sales for Neuropathic Pain in the US by Therapeutic Class, 2012–2022

46%

1%0%24%

10%

19%0%

2012Total: $1.78bn

Calcium alpha-2-delta ligand anticonvulsants

Sodium channel-blocking anticonvulsants

TCAs

SNRI antidepressants

Opioids

Topicals

Other

47%

4%0%16%

8%

20%

5%

2022Total: $2.32bn

Source: GlobalData



Executive Summary

What Do Physicians Think?

When queried about the most challenging aspects

of treating patients with NP, key opinion leaders

(KOLs) were in agreement, citing efficacy and

safety as the key issues.

“Well, I think the efficacy and safety of the drugs

we have available, because with the given

monotherapy, we can have only 50% of the

patients [responding]. And many patients also stop

treatment due to side effects, especially central

nervous system adverse event[s] like dizziness,

nausea, somnolence, and concentration

difficulties.”

[EU] KOL, October 2013

“If you look at all the clinical trials — Lyrica,

duloxetine, opioids, Qutenza — you name it. So,

what is the outcome? Forty percent [of] patients

get 30% pain relief. So, what it means is that 60%

of patients got no pain relief, and even those who

get 30% of pain relief still have plenty of pain. So, if

you have a pain [score] of eight, and your pain is

down to five, you are still in a lot of pain. So,

[when] all [is] said and done, it’s pretty pathetic.”

[US] KOL, September 2013

Another major challenge observed in clinical

practice is the underdosing of key medications.

“These drugs are notoriously underdosed. So, they

come in with 600[mg] or 900[mg] gabapentin, or

75mg pregabalin, per day, which have not been

shown to be effective in those trials. But, I would

not rule out that there are certain patients who are

doing well on low doses, which may not be

placebo, also. But these are all assumptions,

because it has never been demonstrated in clinical

trials that 75mg of pregabalin are effective. Even

150mg are not.”


“If the drug is difficult to titrate, it’s usually that they

[physicians] start treatment, and then they just...I

do not know, they forget titrating. For them, it’s

much easier to handle drugs which actually you

don’t have to titrate that much. So, if you look at

duloxetine, for example, there you don’t have this

danger, because they start usually with 30[mg],

and then they go to 60[mg], and that’s it. But, with

gabapentin, especially, and also with pregabalin,

you need to titrate for longer periods of time. And

maybe that’s too cumbersome for them,

inconvenient. So, it’s much better to have a drug

which doesn’t need that much of a titration.”


Physicians also raised concerns about the lack of

guidance on combination therapies, which are

frequently necessary in the treatment of NP.



Executive Summary

“So, I guess my concern is that this in the real

world, we treat medical illness, including chronic

pain, with multi-drug approaches, and then the

data that we get typically from studies seeking FDA

approval or otherwise is based upon patients who

are being compared with placebo in a single

therapy, and we don’t get guidance about how to

take care of people in the real world. And we also

don’t get the benefit of knowing how these drugs

combine together, [how they] work with each other,

and I think that’s the shame. It is a big obstacle,

because you know the providers of care don’t have

enough studies to support their use of multiple

types of medications at one time — safe or not

safe, what’s likely to help, what’s not likely to help.”

[US] KOL, July 2013

Although physicians indicated a need for novel

therapies, they also pointed out that there are

sometimes financial pressures to prescribe less

expensive drugs first, even though they may be

poorly tolerated by the patient.

“There are two drugs that are approved in the

United States for the management of peripheral

neuropathy: one is duloxetine, and the other one is

pregabalin….Now if you, in the United States, want

to prescribe duloxetine or pregabalin, the third-

party payer or the insurer will refuse to pay for it. [They say] you should use a simpler drug…you

should use a drug like [a] tricyclic [antidepressant]

first. So, if you use a drug like amitriptyline first,

what happens is the patients hate you. You know?

They become constipated, they get erectile

dysfunction, and they get urinary retention. They

get [low] blood pressure, they get a dry mouth —

they hate you for that.”

[US] KOL, August 2013

“Now, what are we doing in clinical practice, we

use a drug like gabapentin [be]cause it is very

cheap today.”

[US] KOL, August 2013

In terms of promising pipeline drugs, Daiichi-

Sankyo’s DS-5565 was highlighted by physicians

as being most promising.

“The Daiichi Sankyo compound, for example, the

calcium [channel] alpha-2-delta [ligand], which…of

course — it’s not a new mechanism, but [it] could

be that this is something which maybe is more

effective than pregabalin, or maybe more safe,

theoretically. They will need to prove this….So, I

think, among the systemically-administered drugs

in the pipelines, I think the Daiichi compound has

the best chance. But it’s nothing new. Not [a] new

mechanism or so.”




Table of Contents

1 Table of Contents

1 Table of Contents ....................................................................................................................... 5

1.1 List of Tables .................................................................................................................... 11

1.2 List of Figures ................................................................................................................... 13

2 Introduction .............................................................................................................................. 14

2.1 Catalyst ............................................................................................................................ 14

2.2 Related Reports................................................................................................................ 14

3 Disease Overview .................................................................................................................... 16

3.1 Clinical Manifestations of Neuropathic Pain – Signs and Symptoms ................................. 18

3.1.1 Painful Diabetic Neuropathy.......................................................................................... 20

3.1.2 Postherpetic Neuralgia.................................................................................................. 21

3.1.3 Trigeminal Neuralgia ..................................................................................................... 21

3.2 Etiology and Pathophysiology ........................................................................................... 22

3.2.1 Etiology ......................................................................................................................... 23

3.2.2 Pathophysiology ........................................................................................................... 24

4 Disease Management .............................................................................................................. 32

4.1 Diagnosis and Treatment Overview .................................................................................. 32

4.1.1 Diagnosis ...................................................................................................................... 32

4.1.2 Treatment Overview and Guidelines ............................................................................. 39

4.2 US .................................................................................................................................... 48

4.2.1 Diagnosis and Referral ................................................................................................. 48

4.2.2 Drug Treatment............................................................................................................. 50



Table of Contents

5 Competitive Assessment .......................................................................................................... 54

5.1 Overview .......................................................................................................................... 54

5.2 Tricyclic Antidepressants .................................................................................................. 58

5.2.1 Overview....................................................................................................................... 58

5.2.2 Efficacy ......................................................................................................................... 59

5.2.3 Safety ........................................................................................................................... 60

5.3 Calcium Channel Alpha-2-Delta Ligands (Anticonvulsants) .............................................. 61

5.3.1 Overview....................................................................................................................... 61

5.3.2 Efficacy ......................................................................................................................... 62

5.3.3 Safety ........................................................................................................................... 64

5.3.4 Lyrica ............................................................................................................................ 64

5.4 Sodium Channel-Blocking Anticonvulsants (TN) ............................................................... 68

5.4.1 Overview....................................................................................................................... 68

5.4.2 Efficacy ......................................................................................................................... 69

5.4.3 Safety ........................................................................................................................... 69

5.5 Serotonin-Norepinephrine Reuptake Inhibitors (Antidepressants) ..................................... 70

5.5.1 Overview....................................................................................................................... 70

5.5.2 Efficacy ......................................................................................................................... 71

5.5.3 Safety ........................................................................................................................... 71

5.5.4 Cymbalta ...................................................................................................................... 71

5.6 Opioids ............................................................................................................................. 74

5.6.1 Overview....................................................................................................................... 74

5.6.2 Efficacy ......................................................................................................................... 75



Table of Contents

5.6.3 Safety ........................................................................................................................... 76

5.6.4 Nucynta ER/Palexia SR ................................................................................................ 76

5.7 Topical Therapies ............................................................................................................. 79

5.7.1 Overview....................................................................................................................... 79

5.7.2 Efficacy ......................................................................................................................... 80

5.7.3 Safety ........................................................................................................................... 80

5.7.4 Lidoderm/Versatis ......................................................................................................... 81

5.7.5 Qutenza ........................................................................................................................ 83

6 Unmet Need and Opportunity ................................................................................................... 87

6.1 Overview .......................................................................................................................... 87

6.2 Physician Knowledge or Awareness ................................................................................. 88

6.2.1 Unmet Need ................................................................................................................. 88

6.2.2 Gap Analysis ................................................................................................................ 89

6.2.3 Opportunity ................................................................................................................... 90

6.3 Diagnostic Challenges ...................................................................................................... 90

6.3.1 Unmet Need ................................................................................................................. 90

6.3.2 Gap Analysis ................................................................................................................ 91

6.3.3 Opportunity ................................................................................................................... 91

6.4 Low Treatment Rate and Underdosing of Medications...................................................... 91

6.4.1 Unmet Need ................................................................................................................. 91

6.4.2 Gap Analysis ................................................................................................................ 93

6.4.3 Opportunity ................................................................................................................... 93

6.5 Unsatisfactory Efficacy and Safety Profiles of Pharmacological Treatments ..................... 94



Table of Contents

6.5.1 Unmet Need ................................................................................................................. 94

6.5.2 Gap Analysis ................................................................................................................ 94

6.5.3 Opportunity ................................................................................................................... 95

6.6 Elderly Patient Population – Drug Tolerability ................................................................... 96

6.6.1 Unmet Need ................................................................................................................. 96

6.6.2 Gap Analysis ................................................................................................................ 96

6.6.3 Opportunity ................................................................................................................... 97

6.7 Rational or Personalized Therapies .................................................................................. 97

6.7.1 Unmet Need ................................................................................................................. 97

6.7.2 Gap Analysis ................................................................................................................ 98

6.7.3 Opportunity ................................................................................................................... 98

7 Pipeline Assessment .............................................................................................................. 100

7.1 Overview ........................................................................................................................ 100

7.2 Promising Drugs in Clinical Development ....................................................................... 101

7.2.1 Eslicarbazepine Acetate ............................................................................................. 103

7.2.2 Topical Clonidine Gel .................................................................................................. 107

7.2.3 Cebranopadol ............................................................................................................. 110

7.2.4 DS-5565 ..................................................................................................................... 113

7.2.5 CNV-2197944 ............................................................................................................. 117

7.2.6 CNV-1014802 ............................................................................................................. 120

7.2.7 Eladur (bupivacaine patch) ......................................................................................... 123

8 Market Outlook ....................................................................................................................... 127

8.1 Drivers and Barriers – Global Issues .............................................................................. 127



Table of Contents

8.1.1 Driver: Aging Population in the 7MM ........................................................................... 127

8.1.2 Driver: Increase in Prevalence and Diagnosis of Type 2 Diabetes Will Grow the PDN

Market ........................................................................................................................ 127

8.1.3 Driver: Approval of New NP Drugs .............................................................................. 128

8.1.4 Barrier: NP Market Dominated by Generics ................................................................ 128

8.1.5 Barrier: Challenges Selecting the Most Relevant Pathophysiological Targets for Drug

Development .............................................................................................................. 128

8.1.6 Barrier: Underserved Trigeminal Neuralgia Indication ................................................. 129

8.1.7 Barrier: Competition from Interventional Therapies ..................................................... 129

8.2 United States .................................................................................................................. 129

8.2.1 Forecast...................................................................................................................... 129

8.2.2 Key Events ................................................................................................................. 140

8.2.3 Drivers and Barriers .................................................................................................... 140

9 Appendix ................................................................................................................................ 143

9.1 Bibliography .................................................................................................................... 143

9.2 Abbreviations .................................................................................................................. 154

9.3 Methodology ................................................................................................................... 159

9.4 Forecasting Methodology ............................................................................................... 159

9.4.1 Diagnosed PDN, PHN, and TN Patients ..................................................................... 159

9.4.2 Percent Drug-Treated Patients ................................................................................... 160

9.4.3 Drugs Included In Each Therapeutic Class ................................................................. 160

9.4.4 Launch and Patent Expiry Dates ................................................................................. 160

9.4.5 General Pricing Assumptions ...................................................................................... 161



Table of Contents

9.4.6 Individual Drug Assumptions....................................................................................... 161

9.4.7 Generic Erosion .......................................................................................................... 165

9.4.8 Pricing of Pipeline Agents ........................................................................................... 165

9.5 Physicians and Specialists Included in This Study .......................................................... 166

9.6 About the Authors ........................................................................................................... 168

9.6.1 Author ......................................................................................................................... 168

9.6.2 Global Head of Healthcare .......................................................................................... 169

9.7 About GlobalData ........................................................................................................... 170

9.8 Disclaimer....................................................................................................................... 170



Table of Contents

1.1 List of Tables

Table 1: Classification of NP Syndromes Based on the Site of Somatosensory Damage................................ 18

Table 2: Signs and Symptoms of NP ............................................................................................................. 19

Table 3: Screening Tools for NP .................................................................................................................... 33

Table 4: NP-Related Signs and Symptoms .................................................................................................... 35

Table 5: Treatment Guidelines for NP............................................................................................................ 40

Table 6: Recommended Drug Therapies for NP Conditions by Line of Therapy ............................................. 46

Table 7: Most Prescribed Drugs for NP by Indication and Line of Therapy in the Global Markets, 2012 .......... 48

Table 8: US – NP Diagnosis and Referral Metrics .......................................................................................... 50

Table 9: US – NP Treatment Metrics ............................................................................................................. 53

Table 10: NNT and NNH for Classes of Oral Drugs used in NP Treatment, 2013 ........................................... 56

Table 11: Select Products Used for NP Treatment, 2013 ............................................................................... 58

Table 12: Product Profile – Lyrica .................................................................................................................. 65

Table 13: Lyrica SWOT Analysis, 2013 ......................................................................................................... 67

Table 14: Product Profile – Cymbalta ............................................................................................................ 72

Table 15: Cymbalta SWOT Analysis, 2013 .................................................................................................... 74

Table 16: Product Profile – Nucynta ER/Palexia SR ...................................................................................... 77

Table 17: Nucynta ER/Palexia SR SWOT Analysis, 2013 .............................................................................. 78

Table 18: Product Profile – Lidoderm/Versatis ............................................................................................... 82

Table 19: Lidoderm/Versatis SWOT Analysis, 2013 ....................................................................................... 83

Table 20: Product Profile – Qutenza .............................................................................................................. 84

Table 21: Qutenza SWOT Analysis, 2013...................................................................................................... 86

Table 22: Unmet Need and Opportunity in NP ............................................................................................... 88

Table 23: NP – Promising Drugs in Clinical Development ............................................................................ 102



Table of Contents

Table 24: Comparison of Drugs in Development for NP, 2014 ..................................................................... 102

Table 25: Product Profile – Eslicarbazepine Acetate .................................................................................... 104

Table 26: Phase II: Efficacy of Eslicarbazepine Acetate in PHN ................................................................... 105

Table 27: Phase II: Efficacy of Eslicarbazepine Acetate in PDN ................................................................... 105

Table 28: Eslicarbazepine Acetate SWOT Analysis, 2013 ........................................................................... 107

Table 29: Product Profile – Topical Clonidine Gel ........................................................................................ 108

Table 30: Topical Clonidine Gel SWOT Analysis, 2013 ................................................................................ 110

Table 31: Product Profile – Cebranopadol ................................................................................................... 111

Table 32: Cebranopadol SWOT Analysis, 2013 ........................................................................................... 113

Table 33: Product Profile – DS-5565 ........................................................................................................... 115

Table 34: DS-5565 SWOT Analysis, 2013 ................................................................................................... 117

Table 35: Product Profile – CNV-2197944 ................................................................................................... 118

Table 36: CNV-2197944 SWOT Analysis, 2013 ........................................................................................... 120

Table 37: Product Profile – CNV1014802 .................................................................................................... 121

Table 38: CNV-1014802 SWOT Analysis, 2013 ........................................................................................... 123

Table 39: Product Profile – Eladur ............................................................................................................... 124

Table 40: Eladur SWOT Analysis, 2013 ....................................................................................................... 126

Table 41: NP Market – Drivers and Barriers, 2012–2022 ............................................................................. 127

Table 42: Sales Forecasts ($) for NP in the United States, 2012–2022 ........................................................ 132

Table 43: Sales Forecasts ($) for PDN in the United States, 2012–2022 ...................................................... 134

Table 44: Sales Forecasts ($) for PHN in the United States, 2012–2022 ...................................................... 136

Table 45: Sales Forecasts ($) for TN in the United States, 2012–2022 ........................................................ 138

Table 46: Key Events Impacting Sales for NP in the United States, 2012–2022 ........................................... 140

Table 47: NP Market – Drivers and Barriers in the United States, 2012–2022 .............................................. 140



Table of Contents

Table 48: Key Launch Dates ....................................................................................................................... 160

Table 49: Key Patent/Exclusivity Expiries .................................................................................................... 161

1.2 List of Figures

Figure 1: Nociceptive Versus Neuropathic Pain ............................................................................................. 17

Figure 2: Etiology and Pathophysiology of NP ............................................................................................... 22

Figure 3: Pain Pathway – Somatosensory System ......................................................................................... 25

Figure 4: Pathophysiological Mechanisms of NP at Different Levels of the Nervous System .......................... 29

Figure 5: Pathophysiological Targets of NP Drugs ......................................................................................... 30

Figure 6: NeuSPIG Diagnostic Certainty Algorithm for NP ............................................................................. 36

Figure 7: General Treatment Algorithm for NP ............................................................................................... 45

Figure 8: Competitive Assessment of Mid-to-Late Stage Pipeline Agents in NP, 2012–2022 ........................ 103

Figure 9: Sales for NP in the United States by Drug Class, 2012–2022........................................................ 133

Figure 10: Sales for PDN in the United States by Drug Class, 2012–2022 ................................................... 135

Figure 11: Sales for PHN in the United States by Drug Class, 2012–2022 ................................................... 137

Figure 12: Sales for TN in the United States by Drug Class, 2012–2022 ...................................................... 139



Introduction

2 Introduction

2.1 Catalyst

The entire neuropathic pain (NP) market is characterized by a high level of unmet need across all

indications, and across the seven major markets (7MM) (US, France, Germany, Italy, Spain, UK,

and Japan). The market, however, is anticipated to grow during the forecast period, from $2.58

billion in 2012 to $3.53 billion in 2022, at a Compound Annual Growth Rate (CAGR) of 3.19%.

During this time, the NP market will be characterized by the following key events, drivers, and

barriers:

Growth in the global market will be driven by the growing incidence of NP as a result of the

increasing elderly population, the increasing prevalence of type 2 diabetes and the resultant

rise in painful diabetic neuropathy (PDN) cases, as well as the market entry of seven pipeline

drugs (DS-5565, eslicarbazepine, cebranopadol, topical clonidine, Eladur, CNV-2197944, and

CNV-1014802).

The fastest-growing market will be Japan, which will end the forecast period accounting for

14% of the market, with projected sales of $491m and a CAGR of 6.38%. This higher-than-

average growth in Japan will be driven by the fact that its population is aging at a faster rate

than any of the other countries in the 7MM, as well as by the delayed launches and continued

growth of Lyrica (pregabalin) and Cymbalta (duloxetine) in Japan.

However, growth in the rest of the 6MM will be greatly impacted by the patent expirations and

subsequent generic erosion of the key leading brands, Lyrica, Cymbalta, and Lidoderm

(lidocaine patch 5%).

2.2 Related Reports

GlobalData (2014). Neuropathic Pain – Global Drug Forecast and Market Analysis to 2022,

April 2014, GDHC70PIDR

GlobalData (2014). Neuropathic Pain – 5EU Drug Forecast and Market Analysis to 2022, April

2014, GDHC240CFR

GlobalData (2014). Neuropathic Pain – Japan Drug Forecast and Market Analysis to 2022,

April 2014, GDHC241CFR



Introduction

GlobalData (2014). Lyrica (Neuropathic Pain) - Forecast and Market Analysis to 2022, April

2014, GDHC405DFR

GlobalData (2014). Cymbalta (Neuropathic Pain) - Forecast and Market Analysis to 2022, April

2014, GDHC406DFR

GlobalData (2014). Nucynta ER/Palexia SR (Neuropathic Pain) - Forecast and Market Analysis

to 2022, April 2014, GDHC407DFR

GlobalData (2014). Lidoderm/Versatis (Neuropathic Pain) - Forecast and Market Analysis to

2022, April 2014, GDHC408DFR

GlobalData (2014). Qutenza (Neuropathic Pain) - Forecast and Market Analysis to 2022, April

2014, GDHC409DFR

GlobalData (2014). Eslicarbazepine acetate (Neuropathic Pain) - Forecast and Market Analysis

to 2022, April 2014, GDHC410DFR

GlobalData (2014). DS5565 (Neuropathic Pain) - Forecast and Market Analysis to 2022, April

2014, GDHC411DFR

GlobalData (2014). Eladur (Neuropathic Pain) - Forecast and Market Analysis to 2022, April

2014, GDHC412DFR

GlobalData (2014). Topical clonidine (Neuropathic Pain) - Forecast and Market Analysis to

2022, April 2014, GDHC413DFR

GlobalData (2014). Cebranopadol (Neuropathic Pain) - Forecast and Market Analysis to 2022,

April 2014, GDHC414DFR

GlobalData (2014). CNV-2197944 (Neuropathic Pain) - Forecast and Market Analysis to 2022,


GlobalData (2014). CNV-1014802 (Neuropathic Pain) - Forecast and Market Analysis to 2022,


GlobalData (2014). Neuropathic Pain - Current and Future Players, April 2014,

GDHC1034FPR


Appendix


9.7 About GlobalData

GlobalData is a leading global provider of business intelligence in the healthcare industry.

GlobalData provides its clients with up-to-date information and analysis on the latest developments

in drug research, disease analysis, and clinical research and development. Our integrated business

intelligence solutions include a range of interactive online databases, analytical tools, reports, and

forecasts. Our analysis is supported by a 24/7 client support and analyst team.

GlobalData has offices in New York, San Francisco, Boston, London, India, Korea, Japan,

Singapore, and Australia.

9.8 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, GlobalData.

Documents

US sample - MarketResearch.com: Market Research ...Neuropathic Pain - US Drug Forecast and Market Analysis to 2022 2 © GlobalData. This report is a licensed product and is not to