Stakeholder Opinions: Melanoma Future treatment will be based on individual tumor gene expression signatures

Introduction

The majority of patients present with early-stage melanoma, when surgery is often curative. Patients with metastatic disease are poorly served by current drugs, with very few approved treatment options and no widely accepted standard of care. A significant unmet need therefore remains for more effective agents, which has made melanoma a popular R&D target.

Scope

*Melanoma overview, including definition, risk factors, epidemiology forecasts and discussion of unmet needs

*Current diagnosis and treatment of melanoma, including drug regimens used by stage and ongoing controversies

*Examination of the late-phase melanoma pipeline and market opportunities for drug developers

*Stakeholder opinions based on qualitative interviews with key opinion leaders in the field of melanoma

Highlights

Most melanoma is diagnosed at an early stage, with surgery proving curative in many patients. For advanced disease, current treatment options are inadequate, with only three approved drugs: interferon alpha-2b in the adjuvant setting, and dacarbazine and interleukin-2 for metastatic disease. Most patients are therefore treated in clinical trials.

Approved products for melanoma confer only mediocre response rates with minimal effects on survival, and high levels of toxicity, thus restricting their use to certain patients. Unmet needs therefore prevail, highlighting the urgent need to develop novel therapeutics offering significant clinical improvements over existing treatment options.

Melanoma has emerged as a relatively popular R&D target for oncology drug developers, with 11 products currently in late-phase development. While incidence of melanoma is not as high as that of the 'big four' tumor types, it is still substantial, which could result in significant financial reward if a pipeline product shows positive results.

Reasons to Purchase

*Identify the limitations of current therapy available to melanoma patients and the potential of future therapy

*Understand current epidemiological trends in melanoma and ongoing treatment controversies

*Assess the opportunities for innovative targeted therapies in the melanoma market, particularly in metastatic disease

Overview 1
Catalyst 1
Summary 1
About Datamonitor healthcare 2
About the Oncology pharmaceutical analysis team 2
Executive Summary 3
Scope of the analysis 3
Datamonitor insight into the melanoma market 3
Related reports 4
Upcoming reports 5
Table of Contents 6
1. Melanoma - Patient Potential 7
Key findings 7
Definition 7
Introduction 7
Melanoma is the fastest growing malignancy among Caucasians 7
Risk factors 8
Exposure to UV light is the greatest risk factor for melanoma 8
Symptoms 9
Increased public awareness of melanoma symptoms can facilitate diagnosis 9
Staging 10
Several staging systems exist for melanoma that incorporate a variety of prognostic factors 10
The large majority of melanoma is diagnosed at a localized stage 11
Prognosis 11
Tumor thickness is the most significant prognostic factor in early-stage melanoma, while the number of positive lymph nodes is crucial in more advanced disease 11
Prevention 13
Changing patterns of exposure to UV radiation may help prevent melanoma 13
Epidemiology 13
Seven major markets 13
Incidence of melanoma will more than double between 2002 and 2019 across the seven major pharmaceutical markets 13
Prevalence of melanoma is significantly larger than incidence due to a high rate of early diagnosis... 15
...which means mortality is also relatively low in comparison to incidence 15
Rest of the world 16
The highest incidence rates of melanoma are seen in Australia and New Zealand 16
The BRIC countries offer significant commercial opportunities due to their large populations 17
Current treatment options 18
Localized melanoma (Stage I/II) 19
Wide excision surgery forms primary treatment for localized melanoma 19
Sentinel lymph node biopsy should be carried out for high-risk patients 20
Adjuvant interferon-alpha is administered to patients with positive lymph nodes 20
Locally advanced melanoma (Stage III) 21
Treatment of locally advanced melanoma is similar to localized therapy, although more aggressive adjuvant therapy is administered 21
Metastatic melanoma (Stage IV) 21
Treatment of metastatic melanoma serves only palliative purposes 21
Resectable metastatic melanoma is treated in a similar fashion to early-stage disease 22
First-line chemotherapy is of limited efficacy in unresectable metastatic melanoma 22
Interleukin-2 is capable of inducing durable complete responses in a small proportion of patients, however, its use is limited due to high levels of toxicity 24
A lack of standard exists for second-line treatment 25
Unmet need in melanoma 25
Current treatment for advanced melanoma has a high risk-to-benefit ratio 25
Few significant advances have been made in drug therapy for metastatic disease 26
Early diagnosis is the key to curative treatment 26
Gene profiling and biomarkers will help individualize treatment approaches 27
2. Melanoma - Market Potential 29
Key findings 29
Current market overview 29
Opportunities and threats 29
Opportunities 30
Incidence of melanoma will continue to increase, particularly in the US and Europe 30
Effective treatment options for adjuvant and metastatic melanoma remain a significant unmet need 30
Potential to target melanoma subpopulations based on tumor gene expression 31
Products in development for melanoma may quality for orphan drug designation 31
Countries such as Australia and New Zealand offer very high commercial potential 31
Threats 31
Increased awareness of symptoms will continue to increase early diagnosis 31
Greater use of biomarkers will reduce overall patient potential 32
3. Pipeline Analysis 33
Key findings 33
Pipeline overview 33
PEG-Intron (pegylated interferon-alpha-2b; Schering-Plough/Merck & Co) 38
Drug profile 38
Development overview 38
Product positioning 40
SWOT analysis 40
Abraxane (albumin-bound paclitaxel; Abraxis Bioscience/Taiho) 41
Drug profile 41
Development overview 42
Product positioning 44
SWOT analysis 44
Taxoprexin (DHA-paclitaxel; Luitpold Pharmaceuticals) 45
Drug profile 45
Development overview 46
Product positioning 47
SWOT analysis 48
Ipilimumab (MDX-010; Medarex/Bristol-Myers Squibb) 48
Drug profile 48
Development overview 49
Product positioning 51
SWOT analysis 52
MAGE-A3 ASCI (astuprotimut-r; GlaxoSmithKline) 53
Drug profile 53
Development overview 54
Product positioning 56
SWOT analysis 57
OncoVEX GM-CSF (BioVex) 57
Drug profile 57
Development overview 58
Product positioning 59
SWOT analysis 60
Tasigna (nilotinib; Novartis) 61
Drug profile 61
Development overview 61
Product positioning 62
SWOT analysis 63
Genasense (oblimersen; Genta) 63
Drug profile 63
Development overview 64
Product positioning 66
SWOT analysis 67
PLX-4032 (Plexxikon/Roche) 68
Drug profile 68
Development overview 69
Product positioning 70
SWOT analysis 71
Tasisulam (LY-573636; Eli Lilly) 72
Drug profile 72
Development overview 73
Product positioning 74
SWOT analysis 75
Allovectin-7 (velimogene aliplasmid; Vical) 76
Drug profile 76
Development overview 76
Product positioning 78
SWOT analysis 78
The future of treatment in melanoma 79
Greater understanding of melanoma evolution should result in a large range of potential drug targets 79
Longer-term control of tumors with reduced toxicity is crucial 80
Improvements in diagnostics and prognostic analysis will enhance cost-effectiveness of treatment 80
Enhanced preventative strategies will ease the disease burden 81
Bibliography 82
Journals 82
Websites 88
Datamonitor reports 91
Other 91
Appendix 92
Contributing experts 92
Conferences attended 92
Report methodology 92
About Datamonitor 93
About Datamonitor Healthcare 93
About the Oncology analysis team 94
Disclaimer 96