Peripheral Neuropathy and Neuropathic Pain, 2008

SUMMARY

Current, pipeline and emerging drugs for the treatment of peripheral neuropathy and neuropathic pain Updated Quarterly

Overview: This report estimates that Peripheral Neuropathy (PN) and Neuropathic Pain (NP) affect 170 to 270 million individuals globally. PN and NP are causally linked to a number of diseases, however diabetes, cancer and HIV alone are expected to increase the prevalence of PN and NP by more than 10% by 2012. PN and NP are areas of significant and critical unmet need. There are no cures for PN and NP is difficult to treat and often unresponsive to all available therapies. Today's armoury of drugs for the treatment of NP shows significant reliance on "second-indication" drugs, which were initially developed to treat other primary indications (e.g. anticonvulsants, antidepressants). This report gives a comprehensive update on all current drugs, together with the entire drug development pipeline, from pre-clinical through to Phase III, Registration and initial Launch. The pipeline includes 80 candidates being developed to treat PN and NP as a primary indication and 60 "second-indication" drugs. More than 300 patents published in the PN and NP field between 2002 and 2008 have also been assessed and presented, together with the identification of potential candidate molecules and drug targets which have not entered the development pipeline, but which may do so in the future. This report was written to provide a comprehensive update on therapeutic developments relating to PN and NP, both in tackling its most serious and debilitating symptoms, but also in targeting and potentially correcting the underlying disease mechanisms. Commercial evaluation and assessments including markets, market size, market sectors, sales and trends relating to PN and NP are also included in this report. Report Description

Drug Targets: Most current and developmental therapies for neuropathic conditions are directed at NP. Moreover, many of today's commonly used drugs in this area were developed for other indications, but subsequently were found to offer useful application in the treatment of NP. These include anticonvulsants, antidepressants and others. These "second indication" drugs represent around 10 pharmacological mechanisms including 5 hydroxytryptamine uptake inhibitors, cannabinoid CB1 agonists, carnitine acetyltransferase stimulants, GABA receptor agonists, NMDA antagonist, opioid mu receptor agonists, sodium channel antagonists, tumour necrosis factor alpha antagonists and others of unidentified pharmacological activity. In contrast, only a few molecules have been developed specifically for NP as a primary indication and these include an aldose reductase inhibitor, a membrane integrity agonist and an opioid kappa receptor agonist. However, the last ten years have seen important advances in the understanding of peripheral neuropathy and neuropathic pain at the biological and pathophysiological level and this is reflected in the numbers of new candidates in the drug development pipeline. Today, there are more than 40 drug types in development for the treatment of PN or NP as primary indications, more than 30 of which are directed at new drug targets. Whilst most of these are directed at NP, a number are targeting the underlying disease mechanisms, offering the hope that NP disease progression may be blocked or even reversed. The development and extension of new and existing molecules for the treatment of NP and PN as second indication drugs continues, and collectively these two groups (i.e. primary + secondary indication drugs) represent over 60 different drug types. Recent patent filings, 2002-2008, show a significant number of other therapeutic opportunities which have not entered the drug development pipeline, but which may do so in the future. This report identifies these candidates on the basis of their mechanism of action, drug target, developmental stage, by company and other relevant areas.

Background and Questions: PN and NP are causally linked to a number of conditions including diabetes, auto immunity, infection, cancer, drugs or toxins, the autonomic nervous system and hereditary diseases. It is estimated in this report that PN and NP currently affect 170 to 270 million individuals globally, figures that are set to increase by more than 10% by 2012. This report discusses the major peripheral neuropathies as well as neuropathic pain, together with prevalence, trends and treatments. Some of the questions considered in this report include: i) which therapies are available for the treatment of PN and NP, their capabilities and failings, unmet need ii) What is happening in the developments pipeline, which candidates are nearest to market iii) what are the prevalences of the major neuropathies and what are the future anticipated trends iv) what strategies are being developed in the treatment of PN and NP, prospects of success and failure v) which companies are developing new therapies for PN and NP vi) what are the current market sizes relating to PN and NP, including market sectors, sales and anticipated growth over the next 5 years

TABLE OF CONTENTS

1. Background

This introductory chapter gives a general overview of peripheral neuropathy (PN) and neuropathic pain (NP) including classification, causes, treatments and unmet need.

• 1.1 Peripheral Neuropathy
  • 1.1.1 Classification
  • 1.1.2 Causes
  • 1.1.3 Treatments
  • 1.1.4 Unmet Need
  • 1.1.5 Discussion
• 1.2 Neuropathic Pain
  • 1.2.1 Classification
  • 1.2.2 Causes
  • 1.2.3 Treatments
  • 1.2.4 Unmet Need
  • 1.2.5 Discussion

2. Prevalence and Trends

PN and NP are causally linked to a number of conditions, several of which are major global diseases such as diabetes, cancer and HIV infection. Chapter 2 gives an overview of the prevalences of PN and NP covering the major disease associations including diabetes, autoimmune disease, viral infections, gastrointestinal conditions, cancer, drug and toxin, autonomic nervous system, nerve compression and hereditary related. The prevalences of PN and NP are assessed for each of these, to allow global levels to be calculated.

• 2.1 Causal Links
  • 2.1.1 Diabetes
  • 2.1.2 Autoimmune
  • 2.1.3 Infection
  • 2.1.3.1 HIV
    • 2.1.3.2 Herpes Zoster
  • 2.1.4 Gastrointestinal
  • 2.1.5 Drugs and Toxins
  • 2.1.6 Cancer
  • 2.1.7 Autonomic
  • 2.1.8 Heredity
  • 2.1.9 Compression
• 2.2 Neuropathic Pain
• 2.3 Trends

3. Therapeutic Pipeline

This chapter gives a detailed presentation of the drug development pipeline, covering approximately 80 drugs being developed to treat PN and NP as primary indications and around 60 candidates, which are second-indication treatments.

• 3.1 Primary Indication Drugs
  • 3.1.1 Launched/Pre-Registration
  • 3.1.2 Phase III
  • 3.1.3 Phase II
  • 3.1.4 Phase I
  • 3.1.5 Pre-clinical
• 3.2 Secondary Indication Drugs
  • 3.2.1 Launched/Pre-Registration
  • 3.2.2 Phase III
  • 3.2.3 Phase II
  • 3.2.4 Phase I
  • 3.2.5 Pre-clinical
• 3.3. Discussion

4. Emerging Technology

This chapter presents and summarises over 300 patent filings relevant to the therapeutic targeting of PN and NP. These were published between Jan 2002 and Jan 2008. This review was been carried out to identify emerging therapeutic opportunities, which have not yet entered the drug development pipeline.

• 4.1 Patents
• 4.2 Drug Targets
• 4.3 Peripheral Neuropathy
• 4.4 Neuropathic Pain
• 4.5 Discussion
• 4.6 Companies/Assignees

5. Markets

An overview of markets relating to PN and NP including products, sales, market size, trends and companies.

• 5.1 Products
• 5.2 Sales
• 5.3 Market Size
• 5.4 Trends
• 5.5 Companies

6. Discussion

Chapter 6 gives a comprehensive overview and discussion on the findings of this report.

• 6.1 Overview
• 6.2 Prevalence and Trends
• 6.3 Unmet Need
  • 6.3.1 Peripheral Neuropathy
  • 3.3.2 Neuropathic Pain
  • 6.3.2 Targeting the Diseases
  • 6.3.4 Reversing the Disease
• 6.4 Drug Targets
• 6.5 Current Treatments
  • 6.5.1 Peripheral Neuropathy
  • 6.5.2 Neuropathic Pain
  • 6.6 Drug Pipeline
  • 6.6.1 Peripheral Neuropathy
  • 6.6.2 Neuropathic Pain
• 6.7 Markets
• 6.8 Conclusions

List of Tables

• Table 1. Drugs and chemical toxins known to cause peripheral neuropathy
• Table 2. Global prevalence of peripheral neuropathy
• Table 3. Drugs and developmental candidates (pre-clinical to launch) for the treatment of PN and NP, as primary indications
• Figure 4. Drugs and developmental candidates (pre-clinical to launch) for the treatment of PN and NP, as secondary indications
• Table 5. Drugs for the treatment of peripheral neuropathy and neuropathic pain
• Table 6. Sales of drugs for the treatment of peripheral neuropathy and neuropathic pain
• Table 7. Candidate drug molecules and potential drug targets which are not identified in the drug development pipeline
• Table 8. Drug targets of candidates in the pipeline, by development phase (primary indications)
• Table 9. Drug targets of candidates in the pipeline, by development phase (secondary indications)
• Table 10. Drug targets of candidates in the pipeline, by development phase (primary and secondary indications)

List of Figures

• Figure 1. Diabetes: The highest national levels (top 5 countries)
• Figure 2. Diabetes: The highest national prevalence (top five countries)
• Figure 3. Candidates at each development stage in the drug pipeline for the treatment of PN and NP, as primary indications
• Figure 4. Primary indication candidates in the drug pipeline for the treatment of PN and NP, by therapeutic group
• Figure 5. Secondary indication candidates in the drug pipeline for the treatment of PN and NP, by therapeutic group
• Figure 6. Secondary indication candidates in the drug pipeline for the treatment of PN and NP, by primary indication therapeutic group
• Figure 7. Candidates at each development stage in the drug pipeline for the treatment of PN and NP, as secondary indications
• Figure 8. Market sectors: PN and NP
• Figure 9. Number needed to treat (NNT) for different types of neuropathic pain: tricyclic antidepressants (Treat A), serotonin noradrenaline reuptake inhibitors (Treat B), gabapentin/pregabalin (Treat C), opioids (Treat D), tramadol (Treat E), NMDA antagonists (Treat F), topical lidocaine (Treat G), cannabinoids (Treat H) and capsaicin (Treat I).

Appendices

• Appendix 1. Patents relating to drug candidates and potential drug targets for the treatment of PN and NP, published from Jan 2002 to Jan 2008