Stakeholder Opinions: Cancer Cachexia - Higher profile needed to unlock market potential of neglected syndrome

Stakeholder Opinions: Cancer Cachexia - Higher profile needed to unlock market potential of neglected syndrome
ABOUT DATAMONITOR HEALTHCARE 2

About the Oncology pharmaceutical analysis team 2

CHAPTER 1 EXECUTIVE SUMMARY 4

Scope of analysis 4

Datamonitor insight into the cancer cachexia market 4

Contributing experts 5

Related reports 6

Upcoming reports 6

CHAPTER 2 CANCER CACHEXIA OVERVIEW 8

Key findings 8

Introduction to cancer cachexia 9

Characteristics of cancer cachexia 9

Cancer cachexia is a syndrome characterized by progressive weight loss 9

Defining cancer cachexia 10

Cancer cachexia lacks a universal definition... 10

...although recent progress has been made towards a definition 11

Progression of cancer cachexia 13

Cancer cachexia covers a broad spectrum of severity 13

Impact of cancer cachexia 14

Survival is lower in cancer patients with cachexia 14

Patients with cancer cachexia show a poorer response to chemotherapy 15

Cancer cachexia adversely affects quality of life 15

Pathophysiology of cancer cachexia 15

Cancer cachexia results from a combination of reduced food intake and altered metabolism driven by host-tumor interactions 15

Reduced food intake 17

Altered metabolism 18

Additional factors contributing to the cachexia syndrome 19

Epidemiology of cancer cachexia 20

Introduction 20

Forecast cancer incidence in the seven major markets 20

Forecast cancer mortality in the seven major markets 21

Cancer cachexia forecasts 23

Weight loss is most common in patients with gastrointestinal tumors and lung cancers 23

Over 1.3 million incurable cancer patients may be potential candidates for palliative treatment for cachexia in the seven major markets in 2009 28

CHAPTER 3 CURRENT TREATMENT OPTIONS AND CONTROVERSIES 30

Key findings 30

Palliative care in oncology 31

Cachexia is one of several symptoms experienced by cancer patients that require palliative care 31

A number of different types of clinician are involved in cancer cachexia management 32

Current treatment options 33

Drugs used to treat cancer cachexia 33

There is a lack of comprehensive guidelines for the treatment of cancer cachexia 34

Progestational agents are widely used for cancer cachexia therapy 37

Megestrol acetate is one of the most extensively studied agents for cancer cachexia treatment 37

Progestational agents improve appetite but have several limitations 38

Corticosteroids were the first therapy option for cancer cachexia 39

Short-term corticosteroid use improves end-stage cancer patients' well being 39

Nutritional support often helps to increase food intake but does not reverse loss of lean body mass 41

Eicosapentaenoic acid has been extensively investigated but has not shown evidence of clinical efficacy 41

Cannabinoids show lower efficacy in cachexia treatment compared to megestrol acetate 42

Advances in cancer cachexia treatment are likely to require a multimodal approach 43

CHAPTER 4 UNMET NEEDS AND CHALLENGES FACING DRUG DEVELOPERS 48

Key findings 48

Unmet needs 48

In the absence of effective therapies, most cancer cachexia patients do not receive any treatment 48

Pharmaceutical and biotech companies appear reluctant to invest in high-risk cachexia clinical trials 49

Patient recruitment to cancer cachexia clinical trials is problematic 50

Cancer cachexia needs a universally accepted definition 51

Progress in cancer cachexia is hindered by the low profile of the condition 52

The visibility of cancer cachexia is low in the medical oncology community 52

The syndrome needs a higher profile in the oncology community in order to move treatment forward and establish a market 53

Improvement is needed in approaches to palliative care for cancer patients 54

Earlier integration of palliative care into management of cancer patients and better coordination between oncologists and nutritionists is needed 54

Low rate of hospice admissions and tendency to administer chemotherapy late in the course of cancer patients' lives has hindered palliative care 55

CHAPTER 5 DRUG DEVELOPMENT 56

Key findings 56

Overview of the cancer cachexia clinical pipeline 57

Pipeline drugs 58

Angiotensin II-targeting agents 58

Vitor (imidapril hydrochloride; Ark Therapeutics) 58

Hormone-based therapies/hormone mimetics 62

Ghrelin, a circulating appetite-stimulating hormone, shows potential in cancer cachexia therapy 62

Anamorelin (RC-1291; Sapphire Therapeutics/Ono) 63

Growth hormone releasing peptide-2 is also able to directly affect appetite and is in development for cancer cachexia 66

Ostarine (MK-2866; GTx/Merck & Co) 66

Anti-inflammatory drugs 69

Thalomid (thalidomide; Celgene) 69

AVR118 (Advanced Viral Research Corp) 73

VT-122 (Vicus Therapeutics) 76

Drugs targeting neurotransmitter receptors 76

Mirtazapine 76

Olanzapine 77

Cancer cachexia clinical trial design 78

Patient selection 78

Variations in entry criteria across clinical trials reflect the lack of consensus over a definition of the syndrome 78

The choice of tumor type is critical to cancer cachexia clinical trial design 79

Endpoints 80

Change in body weight does not give robust evidence of anti-cachexia activity 80

Lean body mass is a more suitable surrogate of anti-cachexia activity than body weight and is currently the most appropriate primary endpoint 81

Survival is rarely used as an endpoint in cachexia trials 82

Quality of life (QOL) is an important endpoint in cancer cachexia clinical trials 82

Measuring physical function potentially provides objective and quantitative evidence of QOL improvement 83

Cancer cachexia awaits a validated biomarker 84

Pharmacoeconomic endpoints could be considered in clinical trial design 85

BIBLIOGRAPHY 86

Bibliography 86

Datamonitor reports 95

APPENDIX 96

List of tables 96

List of figures 96

About Datamonitor 97

About Datamonitor Healthcare 97

About the Oncology analysis team 98

Disclaimer 99

List of Tables

Table 1: Crude incidence rates per 100,000 persons for all types of cancer (excluding non-melanoma skin cancer) in the seven major markets, 2002 20

Table 2: Forecast total incidence of all types of cancer (excluding non-melanoma skin cancer ) in the seven major markets, 2009-2018 21

Table 3: Crude mortality rates for all types of cancer (excluding non-melanoma skin cancer) in the seven major markets, 2002 21

Table 4: Forecast total mortality from all types of cancer (excluding non-melanoma skin cancer ) in the seven major markets, 2009-2018 22

Table 5: Percentage of cancer patients with weight loss across different tumor types 23

Table 6: Number of patients diagnosed with cancer experiencing weight loss by tumor type in the seven major markets, 2009 24

Table 7: Forecast number of patients diagnosed with cancer who will experience weight loss during the course of their disease in the seven major markets, 2009-2018 26

Table 8: Forecast number of cancer patients experiencing weight loss in the last 1-2 weeks of life in the seven major markets, 2009-2018 28

Table 9: Current treatment options for cancer cachexia, 2009 34

Table 10: Pipeline drugs in clinical development for cancer cachexia, 2009 57

Table 11: Vitor: key historical events, 1993-2008 59

Table 12: Anamorelin: key historical events, 2001-07 64

Table 13: Ostarine: key historical events, 2006-08 67

Table 14: Thalomid: key historical events, 1996-2008 70

Table 15: AVR118: key historical events, 2003-08 74

Table 16: Ongoing trials in cancer cachexia, 2009 74

Table 17: VT-122: key historical events, 2007-08 76

List of Figures

Figure 1: Characteristics associated with cancer cachexia 10

Figure 2: Spectrum of cancer cachexia severity and approximate associated survival 14

Figure 3: Schematic overview of cancer cachexia pathophysiology 17

Figure 4: Number of patients diagnosed with cancer experiencing weight loss by tumor type in the seven major markets, 2009 25

Figure 5: Forecast number of patients diagnosed with cancer who will experience weight loss during the course of their disease in the seven major markets, 2009-2018 27

Figure 6: Forecast number of cancer patients experiencing weight loss in the last 1-2 weeks of life in the seven major markets, 2009-2018 29

Figure 7: Cancer patient treatment flow chart 32

Figure 8: National Comprehensive Cancer Network (NCCN) guidelines for cancer cachexia patients with long life expectancy 35

Figure 9: National Comprehensive Cancer Network (NCCN) guidelines for cancer cachexia patients with short life expectancy 36

Figure 10: Placebo-controlled study of megestrol acetate in cancer cachexia patients 38

Figure 11: Phase III study of megestrol acetate versus dexamethasone and fluoxymesterone 40

Figure 12: Phase III of eicosapentaenoic acid (EPA) in gastrointestinal or lung cancer patients with cachexia 42

Figure 13: Phase III trial of dronabinol versus megestrol acetate in advanced cancer patients 43

Figure 14: Phase III study of eicosapentaenoic acid (EPA) with or without megestrol acetate in cancer cachexia 44

Figure 15: Study of megestrol acetate and ibuprofen combination in gastrointestinal cancer patients with cachexia 45

Figure 16: Phase III trial comparing various treatment options in advanced cancer patients with cachexia 46

Figure 17: Summary of unmet needs in cancer cachexia, 2009 48

Figure 18: Pilot Phase III trial of Vitor in cachectic non-small cell lung cancer patients 60

Figure 19: Phase II/III trial of Vitor in advanced cancer patients with cachexia symptoms 61

Figure 20: Phase II study of anamorelin in cachectic patients with advanced solid tumor cancers 65

Figure 21: Phase II study of Ostarine in cancer cachexia 68

Figure 22: Phase II trial of Thalomid in advanced cancer patients 71

Figure 23: Randomized trial of Thalomid in pancreatic cancer patients with cachexia 72

Figure 24: Results of Phase I/II study of AVR118 in cancer and AIDS cachexia 75

Figure 25: Phase II trial of mirtazapine in advanced cancer patients 77