Evolution in the Pain Therapy Drugs Market: Nociceptive and Neuropathic Drug Development

Pain Therapy Drugs Market :
As the market evolves over the next decade current market leaders will lose patent expiry and become subject to generic competition. What’s in the pipeline and which companies and products will prosper?

Pain affects around 1.5 billion people worldwide. In most cases, pain is temporary and easily treated with commonly available analgesics. For some people, however, pain is a debilitating, chronic condition. In Europe, an estimated 20% of the population suffers from chronic pain. As the population ages, the number of people with chronic pain is increasing, particularly from conditions such as osteoarthritis. Chronic pain is also associated with cancer. An estimated 30% of all cancer patients are in pain with the proportion more than doubling among people with late-stage cancer. In recent years, drug development in pain therapy has been focused mainly on reformulations of existing therapies and alternative modes of drug delivery in order to improve the safety and efficacy of existing drug groups.

Drugs of the future
This report identifies 75 agents in clinical development for pain indications, of which 26 are in development for neuropathic pain. Among these, six are specifically targeting postherpetic neuralgia. Other indications specified, include: diabetic peripheral neuropathy, central neuropathic pain due to spinal cord injury or multiple sclerosis (MS), neuropathic pain in cancer, lumbosacral radiculopathy, and painful neuropathies affecting AIDS patients. Nociceptive pain indications being targeted by developers,
include: osteoarthritis pain and chronic low back pain.

This report answers key questions on:

• What is the current clinical understanding of pain?
• What is the status of, and commercial prospects for, currently available pain therapies?
• What drugs are in the pipeline and what is their status?
• Which companies are set to win, and which to lose, as the pain sector develops over the next 5 years?

While highly competitive, pain remains a sector of high unmet clinical need with excellent opportunities in niche markets
While the pain market is fragmented and highly competitive, it remains an area of high unmet need as current therapies are often less than effective and/or have undesirable side-effects. A number of new drugs are poised to take market share, with Palexia/Nucynta (tapentadol) widely tipped to be among the up and coming market leaders. As the market continues to evolve over the next decade, the current market leaders will lose patent expiry and become subject to generic competition and consequent price erosion. It is generally agreed that sales of novel treatments are unlikely to entirely replace the revenue lost following patent expiry of the current top five. However, there will be opportunities in underserved niche market segments, particularly neuropathic pain, which typically fails to respond adequately to conventional analgesics.

Lessons in OTC switching
The pain sector is ideal for OTC switching and is a means of mitigating the effects of generic competition. A good example is Novartis’ former blockbuster, Voltaren (diclofenac), which was re-launched as an OTC product in 1999 and is now the company’s leading OTC brand. The prescription product still maintains relatively strong sales, however, due to long-term trust in the brand in markets in Latin America, the Middle East, Africa and Asia. In 2010, sales of Voltaren (excluding OTC) amounted to US$791 million.

Tackling Opioid Abuse
Opioid abuse is a widely known problem, particularly in the US. Prescription drug abuse in the US is the country’s fastest growing drug abuse problem and has been directly correlated to a dramatic increase in the number of prescriptions filled for opioids. According to the Office of National Drug Control Policy, between 1997 and 2007, the milligram-per-person use of prescription opioids in the US increased from 74mg to 369mg while the number of prescriptions for opioids dispensed by retail pharmacies rose from 174 million in 2000 to 257 million in 2009. In 2007, the number of deaths from unintentional overdose of opioids in the US was 11,499, compared with just 2,901 in 1999. Despite the potential for abuse, however, opioids remain important in the treatment of moderate to severe chronic pain and several companies such as Acura and Collegium are developing formulations aimed at deterring abuse.

"...Who are the players, and what are the products, that will shape this US$46 billion sector over the next 5 years...?"

Questions answered

• To what extent will generic competition affect Lilly’s leading pain drug Cymbalta from 2013 onwards?
• What legal challenges must Pfizer overcome if Lyrica is to achieve its forecast sales of US$4.2 billion in 2017?
• What clinical benefits does GW Pharmaceuticals’ Sativex offer in the MS market and does the product have new indication opportunities?
• Grünenthal’s Palexia/Nucynta (also marketed by Johnson & Johnson in the US) is widely tipped for rapid growth due to its dual action and better tolerability profile over its opioid competitors. But will these benefits be enough to challenge the lower price of generically available competitors in the future?
• How did Pfizer improve its market share in 2011 in the pain sector?
• What techniques are being employed to overcome opioid abuse?
• Who is developing products that target cancer-related pain?
• What do the market leaders have in their Phase I/II pipelines?

Table Of Contents

Foreword  1

Executive Summary  3

Market Analysis  4

Current Market  4
Leading Pain Therapies  5
Opioid Analgesics  6
FDA Risk Evaluation and Mitigation Strategy for Opioids  7
Leading Companies  8
Endo Pharmaceuticals  8
Eli Lilly  8
Grünenthal  8
Johnson & Johnson  9
Pfizer  9
Purdue Pharma/Mundipharma/Napp Pharmaceuticals  9

Types Of Pain  9
Acute and Chronic Pain  9
Nociceptive and Neuropathic Pain  10
Psychogenic Pain  10

Current Guidance And Treatment Options  11
Cancer Pain  11
The World Health Organization’s Pain Ladder  11
Cancer Pain Complexity and a Case for Change  11
Neuropathic Pain  12

Future Market  14
What’s in the Pipeline?  14
Opioid Abuse Deterrents  17
Acura Pharmaceuticals’ Aversion Technology  18
Collegium Pharmaceutical’s DETERx Technology  18
Durect’s Oradur Technology  19
Grünenthal’s Tamper Resistant Formulation  19

Competitor Ratio Analysis  20

Product Analysis  22

Neuropathic Pain  22
Cymbalta (duloxetine)  22
Mode of Action  22
Approvals  22
Lifecycle Development  23
Proof of Concept/Clinical Data 23
Diabetic Peripheral Neuropathic Pain  23
Chronic Low Back Pain  24
Fibromyalgia 24
Development Risks  24
Company Expertise  24
Competition within the Marketplace  24
Patents  25
Generic Company Activity  25
Competitor Ratio Analysis  26
Sales Forecast  26

Lyrica (pregabalin)  28
Mode of Action  28
Approvals  28
Lifecycle Development  28
Proof of Concept/Clinical Data 29
Central neuropathic pain following spinal cord injury  29
Postherpetic neuralgia and neuropathic pain associated with diabetic peripheral neuropathy  29
Fibromyalgia 29
Development Risks  29
Company Expertise  30
Competition within the Marketplace  30
Patents  30
Generic Company Activity  30
Competitor Ratio Analysis  31
Sales Forecast  31

Lidoderm/Versatis (lidocaine)  33
Mode of Action  33
Approvals  33
Lifecycle Development  33
Proof of Concept/Clinical Data 33
Development Risks  34
Company Expertise  34
Competition within the Marketplace  34
Patents  34
Generic Company Activity  35
Watson Pharmaceuticals  35
Mylan  35
Endo’s Citizen Petition Regarding Bioequivalence  36
Competitor Ratio Analysis  36
Sales Forecast  36

Qutenza/NGX-1998 (capsaicin)  38
Mode of Action  38
Approvals  38
Lifecycle Development  38
Qutenza 38
NGX-1998 38
Proof of Concept/Clinical Data  39
Development Risks  39
Company Expertise  39
Competition within the Marketplace  40
Patents  40
Competitor Ratio Analysis  40

Sativex (nabiximols)  41
Mode of Action  41
Approvals  41
Development  41
Proof of Concept/Clinical Data  41
Development Risks  42
Company Expertise  42
Competition within the Marketplace  43
Competitor Ratio Analysis  43

In Development For Neuropathic Pain  44
Horizant (gabapentin enacarbil)  44
Mode of Action  44
Approvals  44
Lifecycle Development  44
Proof of Concept/Clinical Data  44
Development Risks  45
Company Expertise  45
Competition within the Marketplace  45
Patents  45
Competitor Ratio Analysis  46

Nuedexta (dextromethorphan+quinidine)  47
Mode of Action  47
Approvals  47
Lifecycle Development  47
Proof of Concept/Clinical Data  47
Development Risks  48
Company Expertise  48
Competition within the Marketplace  48
Patents  48
Generic Company Activity  49
Competitor Ratio Analysis  49

Zebinix (eslicarbazepine acetate)  50
Mode of Action  50
Approvals  50
Lifecycle Development  50
Proof of Concept/Clinical Data 50
Development Risks  50
Company Expertise  51
Competition within the Marketplace  51
Competitor Ratio Analysis  51

AGN-214868  52
Mode of Action  52
Current Status  52
Proof of Concept/Clinical Data 52
Development Risks  52
Company Expertise  52
Competition within the Marketplace  53
Competitor Ratio Analysis  53

ARA290  54
Mode of Action  54
Current Status  54
Proof of Concept/Clinical Data 54
Development Risks  54
Company Expertise  54
Competition within the Marketplace  54
Competitor Ratio Analysis  55

AZD2066  56
Mode of Action  56
Current Status  56
Proof of Concept/Clinical Data 56
Development Risks  56
Company Expertise  56
Competition within the Marketplace  56
Competitor Ratio Analysis  57

AZD2423  58
Mode of Action  58
Current Status  58
Proof of Concept/Clinical Data 58
Development Risks  58
Company Expertise  58
Competition within the Marketplace  59
Competitor Ratio Analysis  59

E2007 (perampanel)  60
Mode of Action  60
Current Status  60
Proof of Concept/Clinical Data  60
Development Risks  60
Company Expertise  61
Competition within the Marketplace  61
Competitor Ratio Analysis  61

EMA401  62
Mode of Action  62
Current Status  62
Proof of Concept/Clinical Data  62
Development Risks  62
Company Expertise  62
Competition within the Marketplace  62
Competitor Ratio Analysis  63

KRN5500  64
Mode of Action  64
Current Status  64
Proof of Concept/Clinical Data  64
Development Risks  64
Company Expertise  64
Competition within the Marketplace  65
Competitor Ratio Analysis  65

NT-11624 (dimiracetam)  66
Mode of Action  66
Current Status  66
Proof of Concept/Clinical Data  66
Development Risks  66
Company Expertise  67
Competition within the Marketplace  67
Competitor Ratio Analysis  67

CNV1014802  68
Mode of Action  68
Current Status  68
Proof of Concept/Clinical Data  68
Development Risks  68
Company Expertise  68
Competition within the Marketplace  68
Competitor Ratio Analysis  69

Nociceptive Pain  70
Celebrex (celecoxib)  70
Mode of Action  70
Approvals  70
Lifecycle Development  71
Proof of Concept/Clinical Data 71
Gastrointestinal Events  71
Development Risks  71
Cardiovascular and Gastrointestinal Risks  71
Company Expertise  72
Competition within the Marketplace  72
Patents  72
Generic Company Activity  73
Competitor Ratio Analysis  73
Sales Forecast  73

Duragesic (fentanyl)  75
Mode of Action  75
Approvals  75
Proof of Concept/Clinical Data 75
Development Risks  75
Company Expertise  76
Competition within the Marketplace  76
Competitor Ratio Analysis  76
Sales Forecast  76

OxyContin (oxycodone)  78
Mode of Action  78
Approvals  78
Proof of Concept/Clinical Data 78
Development Risks  78
Company Expertise  79
Competition within the Marketplace  79
Patents  79
Generic Company Activity  79
Competitor Ratio Analysis  80
Sales Forecast  80

Oxecta (oxycodone)  82
Mode of Action  82
Approvals  82
Lifecycle Development  82
Proof of Concept/Clinical Data 82
Development Risks  82
Company Expertise  83
Competition within the Marketplace  83
Patents  83
Competitor Ratio Analysis  84

Opana/Opana ER (oxymorphone)  85
Mode of Action  85
Approvals  85
Lifecycle Development  85
Proof of Concept/Clinical Data  86
Development Risks  86
Company Expertise  86
Competition within the Marketplace  86
Patents  86
Generic Company Activity  87
Competitor Ratio Analysis  88
Sales Forecast  88

Palexia/Nucynta (tapentadol)  90
Mode of Action  90
Approvals  90
Lifecycle Development  90
Proof of Concept/Clinical Data  91
Development Risks  91
Company Expertise  91
Competition within the Marketplace  92
Patents  92
Competitor Ratio Analysis  92
Sales Forecast  93

Vimovo (naproxen+esomeprazole)  94
Mode of Action  94
Approvals  94
Proof of Concept/Clinical Data  94
Development Risks  95
Company Expertise  95
Competition within the Marketplace  95
Patents  95
Generic Company Activity  96
Competitor Ratio Analysis  97
Sales Forecast  97

BuTrans/Norspan (buprenorphine)  99
Mode of Action  99
Approvals  99
Lifecycle Development  99
Proof of Concept/Clinical Data 99
Development Risks  100
Company Expertise  100
Competition within the Marketplace  101
Patents  101
Competitor Ratio Analysis  101

In Development For Nociceptive Pain  102
Remoxy (oxycodone)  102
Mode of Action  102
Current Status  102
Proof of Concept/Clinical Data 102
Development Risks  103
Company Expertise  103
Competition within the Marketplace  103
Competitor Ratio Analysis  104

MoxDuo IR (morphine+oxycodone)  105
Mode of Action  105
Current Status  105
Proof of Concept/Clinical Data 105
Development Risks  105
Company Expertise  105
Competition within the Marketplace  106
Competitor Ratio Analysis  106

ALO-02 (oxycodone+naltrexone)  107
Mode of Action  107
Current Status  107
Proof of Concept/Clinical Data 107
Development Risks  108
Company Expertise  108
Competition within the Marketplace  108
Competitor Ratio Analysis  108

COL-003 (oxycodone)  109
Mode of Action  109
Current Status  109
Proof of Concept/Clinical Data 109
Development Risks  109
Company Expertise  110
Competition within the Marketplace  110
Competitor Ratio Analysis  110

Eladur (bupivacaine)  111
Mode of Action  111
Current Status  111
Proof of Concept/Clinical Data  111
Development Risks  111
Company Expertise  111
Competition within the Marketplace  112
Competitor Ratio Analysis  112

Zohydro (hydrocodone bitartrate)  113
Mode of Action  113
Current Status  113
Proof of Concept/Clinical Data  113
Development Risks  113
Company Expertise  114
Competition within the Marketplace  114
Competitor Ratio Analysis  114

NP2 Enkephalin  115
Mode of Action  115
Current Status  115
Proof of Concept/Clinical Data  115
Development Risks  115
Company Expertise  115
Competition within the Marketplace  116
Competitor Ratio Analysis  116

Tanezumab  117
Mode of Action  117
Current Status  117
Proof of Concept/Clinical Data  117
Development Risks  118
Company Expertise  118
Competition within the Marketplace  118
Competitor Ratio Analysis  118

ARRY-797  119
Mode of Action  119
Current Status  119
Proof of Concept/Clinical Data  119
Development Risks  119
Company Expertise  119
Competition within the Marketplace  119
Competitor Ratio Analysis  12

Sources  121
Espicom Sources  121
Others  121

Index  122

List Of Tables

Global Sales of Branded Drugs Used in Pain Management, 2010 (US$ Million)  5
Drugs Approved for Neuropathic Pain in the US and EU  13
Drugs in Development for Pain  14
Competitor Ratio Analysis Summary  21
Cymbalta US Patents  25
FDA Tentative ANDA Approvals for Duloxetine  26
Cymbalta Sales, 2010-2017 (US$ Million)  26
Lyrica US Patents  30
FDA Tentative ANDA Approvals for Pregabalin  31
Lyrica Sales, 2010-2017 (US$ Million)  31
Lidoderm US Patents  35
Lidoderm/Versatis Sales by Company, 2010-2017 (EUR & US$ Million)  37
Qutenza US Patents  40
Horizant US Patents  45
Nuedexta US Patents  49
Celebrex US Patents  72
Celebrex/Celecox Sales by Company, 2010-2017 (¥ & US$ Million)  74
Duragesic Sales, 2010-2017 (US$ Million)  76
OxyContin US Patents  79
OxyContin Sales, 2010-2017 (US$ Million)  80
Oxecta US Patents  83
Opana ER US Patents  87
FDA ANDA Approvals for Oxymorphone ER  87
Opana/Opana ER Sales, 2010-2017 (US$ Million)  88
Nucynta US Patents  92
Palexia/Nucynta Sales, 2010-2017 (US$ Million) 93
Vimovo US Patents  96
Vimovo Sales, 2011-2017 (US$ Million)  97
BuTrans US Patents  101

List Of Figure

Global Pain Market by Country, 2011 (%) 4
NHS Opioid Analgesic Prescriptions by Volume, 2010 (%) 6
NHS Opioid Analgesic Prescriptions by Cost, 2010 (%) 7
Leading Companies in Pain Management by Revenue (%) 8
Cymbalta Sales Trend, 2007-2017 27
Lyrica Sales Trend, 2007-2017 32
Lidoderm/Versatis Sales Trend, 2008-2017 37
Celebrex/Celecox Sales Trend, 2007-2017 74
Duragesic Sales Trend, 2007-2017 77
OxyContin Sales Estimate, 2010-2017 81
Opana/Opana ER Sales Trend, 2007-2017 89
Palexia/Nucynta Sales Trend, 2009-2017 93
Vimovo Sales, 2011-2017 98