Market Report Source

Overview

Introduction

In spite of generic Actiq competition, Cephalon’s reign of the breakthrough pain market will be secured in the short-term with sales of its follow-on brand Fentora. From 2008, however, a number of fast-acting analgesics will enter the arena and battle for market share; this and other growth drivers will see the market more than double from 2005 to reach an estimated $2.5 billion in 2016.

Scope

*Discussion and quantification of the patient potential and market size of breakthrough pain in both malignant and non-malignant diseases *Assessment of the unmet clinical needs in breakthrough pain as validated by interviewed international opinion leaders *Detailed overview and assessment of key drugs in Phase II and above clinical development, including Fentora, Rapinyl, and BEMA Fentanyl *Ten-year sales forecasts to 2016 for key pipeline products

Highlights

Relatively high unmet clinical need, additional patient groups, the launch of new products, and no further key patent expiries within the next ten years will see the breakthrough pain market more than double from 2005 to reach $2.5 billion in 2016.

As well as for oral transmucosal fentanyl products, opportunities also exist for non-oral analgesics. Intranasal and inhaled technology may provide convenient and fast acting analgesia and are potentially suitable for self-administration in the lucrative outpatient setting.

A key growth strategy will be to gain initial approval for cancer breakthrough pain and then drive sales in additional indications through off-label use or regulatory approval. Key non-malignant applications for fast acting analgesics include breakthrough pain in post-operative pain, chronic low back, and osteoarthritic pain.

Reasons to Purchase

*Explore the strategies that have made Cephalon the market leading company in breakthrough pain *Examine the potential for intranasal and inhaled analgesics and what other factors companies are using to differentiate their products *Analyze the competitive environment at the time of product launch and identify lucrative gaps in the market

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Central Nervous System pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the breakthrough pain market

Summary

CHAPTER 2 PATIENT POTENTIAL

Definition of breakthrough pain

Epidemiology of breakthrough pain

Breakthrough cancer pain

Breakthrough pain is more prevalent in advanced cancer stages

Patients have between four to seven episodes per day

Breakthrough pain is a common cause of hospital admissions

Breakthrough pain in non-malignant diseases

Breakthrough pain also occurs in neuropathic, musculoskeletal, visceral and postoperative pain syndromes

Market sizing assumptions and caveats

Unmet need in breakthrough pain

Need for an analgesic that acts rapidly, predictably, and just for the duration of a breakthrough pain episode

Need for quick, simple, and safe drug administration

Need for improved convenience, cost, and safety of patient-controlled analgesia

Need to reduce the abuse and overdosing potential of opioids

Need to minimize opioid-related adverse events

Need for standardized diagnosis and assessment tools for breakthrough pain

CHAPTER 3 R&D APPROACH

Classification of pipeline products

Majority of pipeline products are reformulations of existing opioids

Oral transmucosal opioids

Oral inhaled opioids

Intranasal opioids

Subcutaneous opioids

Transdermal opioids

Clinical trial design in breakthrough pain

Actiq clinical trials set the standard

Actiq pivotal trial overview

Clinical trial endpoints in breakthrough pain

Primary endpoints: the Brief Pain Inventory is often used to assess pain in cancer patients

Secondary endpoints: economic and quality-of-life measures are important

CHAPTER 4 BREAKTHROUGH PAIN PIPELINE ANALYSIS

Pipeline overview

The success of Actiq and established efficacy make fentanyl a popular target

Key companies involved in the breakthrough pain pipeline

Cephalon: leading the way in breakthrough pain

Strong CNS focus is good for market growth

Follow-on drug strategy can offset generic incursion

Drug delivery expertise provides positive long term outlook

Leverage oncology resource to reach out to key treatment decision makers

Strategies for success

Broaden customer base with key additional indications

Back pain

Postoperative pain

Neuropathic pain

Osteoarthritis

Refractory migraine

CHAPTER 5 LATE-STAGE DRUG ANALYSIS & FORECASTS

Overview

Late stage pipeline summary

Definition of current comparator therapy

Comparison of key compounds

Comparative forecasts

Fentora

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

Rapinyl

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

BEMA Fentanyl

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

Intranasal morphine gluconate, Nastech

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

Rylomine (intranasal morphine)

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

PMI-150 (intranasal ketamine)

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

Fentanyl Taifun (oral inhaled fentanyl)

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

AeroLEF (oral inhaled fentanyl)

Profile

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Datamonitor drug assessment summary

Other drugs

Titragesia (transdermal fentanyl patch)

Pain pen (subcutaneous hydromorphone injection)

TPM-01 (transdermal morphine cream)

AD-923 (sublingual fentanyl)

Nasalfent (intranasal fentanyl)

BIBLIOGRAPHY

Journal articles and conference abstracts

Websites

APPENDIX A

Contributing experts

Sales forecasts

Competitive positioning analysis of pipeline breakthrough pain drugs

Methodology

Datamonitor forecast methodology and assumptions

Product forecasts

Estimation of launch dates

Patient expiry and generic assumptions

Definition of a standard unit

APPENDIX B

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare’s therapy area capabilities

About the CNS analysis team

Disclaimer

List of Tables

Table 1: Prevalence of breakthrough pain across the seven major markets, 2006

Table 2: Estimation of the breakthrough pain market across the seven major markets, 2005

Table 3: Characteristics of immediate-release opioids useful for breakthrough pain

Table 4: Primary opioid-related adverse events for 130 patients initially enrolled in the trial of Actiq for cancer-related breakthrough pain

Table 5: Characteristics of patients enrolled in the Farrar et al. (1998) Actiq trial

Table 6: Number of R&D projects in each class split by mode of delivery, 2006

Table 7: Clinical R&D pipeline for breakthrough pain drugs, 2006

Table 8: Cephalon’s inline and pipeline pain product range, 2006

Table 9: Key products in late-stage R&D pipeline for breakthrough pain, 2006

Table 10: Primary opioid-related adverse events for 130 patients initially enrolled in the trial of Actiq for cancer-related breakthrough pain

Table 11: Pharmacokinetic parameters in adult subjects receiving the various doses of Actiq

Table 12: Fentora product claims on http://www.fentora.com

Table 13: Key approval and launch dates impacting Fentora’s revenue forecast, 2006-2016

Table 14: Key approval and launch dates impacting Rapinyl’s revenue forecast, 2006-2016

Table 15: BEMA technology product claims taken from BioDelivery Sciences’s website

Table 16: Key approval and launch dates impacting BEMA Fentanyl revenue forecast, 2006-2016

Table 17: Key approval and launch dates impacting intranasal morphine gluconate revenue forecast, 2006-2016

Table 18: Key approval and launch dates impacting Rylomine revenue forecast, 2006-2016

Table 19: Key approval and launch dates impacting PMI-150 revenue forecast, 2006-2016

Table 20: Key approval and launch dates impacting Fentanyl Taifun revenue forecast, 2006-2016

Table 21: Key approval and launch dates impacting AeroLEF revenue forecast, 2006-2016

Table 22: Datamonitor’s forecast sales of pipeline breakthrough pain drugs and the total breakthrough pain market across the seven major markets ($m), 2006-2016

Table 23: Summary of commercial and research/clinical attractiveness of late-stage drugs for breakthrough pain

Table 24: Estimation of launch dates by phase of development

Table 25: Estimated generic discounts by country, 2006*

Table 26: Estimates of brand erosion by following patent expiry by country

List of Figures

Figure 1: Datamonitor’s breakthrough pain forecast market across the seven major markets, 2006-2016

Figure 2: Datamonitor breakthrough pain drug assessment summary, 2006-2016

Figure 3: The different types of breakthrough pain

Figure 4: The current versus ideal approach to breakthrough pain treatment

Figure 5: Onset of action versus duration of action of opioid formulations

Figure 6: Actiq study design

Figure 7: Breakthrough pain drug pipeline by development phase and formulation, 2006

Figure 8: Breakdown of the breakthrough pain pipeline by formulation, 2006

Figure 9: Breakdown of the pipeline by molecule, 2006

Figure 10: Difference in pain intensity between Actiq and placebo (ITT analysis)

Figure 11: Pain relief of Actiq versus placebo (ITT analysis)

Figure 12: Datamonitor’s comparative forecast of sales for key products across the seven major markets ($m), 2006-2016

Figure 13: Pain intensity difference of Fentora versus placebo over time

Figure 14: Comparison of pain intensity difference scores of Actiq versus Fentora

Figure 15: Datamonitor’s forecast of sales for Fentora across the seven major markets ($m), 2006-2016

Figure 16: Datamonitor’s competitive positioning analysis for Fentora, 2006-2016

Figure 17: Datamonitor’s forecast of sales for Rapinyl across the seven major markets ($m), 2006-2016

Figure 18: Datamonitor’s competitive positioning analysis for Rapinyl, 2006-2016

Figure 19: Datamonitor’s forecast of sales for BEMA Fentanyl across the seven major markets ($m), 2006-2016

Figure 20: Datamonitor’s competitive positioning analysis for BEMA Fentanyl, 2006-2016

Figure 21: Datamonitor’s forecast of sales for Intranasal morphine gluconate across the seven major markets ($m), 2006-2016

Figure 22: Datamonitor’s competitive positioning analysis for Intranasal morphine gluconate, 2006-2016

Figure 23: Datamonitor’s forecast of sales for Rylomine across the seven major markets ($m), 2006-2016

Figure 24: Datamonitor’s competitive positioning analysis for Rylomine, 2006-2016

Figure 25: PMI-150 study design

Figure 26: Datamonitor’s forecast of sales for PMI-150 across the seven major markets ($m), 2006-2016

Figure 27: Datamonitor’s competitive positioning analysis for PMI-150, 2006-2016

Figure 28: Datamonitor’s forecast of sales for Fentanyl Taifun across the seven major markets ($m), 2006-2016

Figure 29: Datamonitor’s competitive positioning analysis for Fentanyl Taifun, 2006-2016

Figure 30: Datamonitor’s forecast of sales for AeroLEF across the seven major markets ($m), 2006-2016

Figure 31: Datamonitor’s competitive positioning analysis for AeroLEF, 2006-2016