Pipeline/Commercial Insight: Supportive Care in Oncology - Significant growth opportunities exist in new supportive care indications
Introduction
Supportive care can be defined as those products used to prevent and/or treat the adverse side effects that arise as a result of the tumor itself or administration of anticancer therapies, in particular cytotoxic chemotherapy. While the antihormonal therapies and novel molecular targeted therapies do not exist without some toxicity, these are not as severe as those associated with chemotherapy.
Scope
Overview of the current oncology supportive care market, including profiles of key marketed products and events impacting each during 200616 Examination of the oncology supportive care pipeline with in-depth clinical and commercial profiles of Phase III and some key Phase II candidates Seven-market sales forecasts from 2006 to 2016 for branded oncology supportive care products and key pipeline candidates Detailed discussion of key strategic issues in the oncology supportive care market, including one commercial impact case study
Highlights
The oncology supportive care market is forecast to undergo slightly positive growth at a CAGR of 0.6%, from a seven-market sales total of $13,763m in 2006 to $14,679m in 2016. This low level of growth is largely due to an increasing level of patent expiry and generic competition, including the impending launch of biosimilars in the EU. The erythropoietins class has come under increasing levels of scrutiny of late due to emerging doubts over safety of these products. As a result the FDA and EMEA are recommending more restrictive conditions for use and increased monitoring of patients. It is expected that sales of these products will suffer as a result of these restrictions. Any significant future growth in the oncology supportive care market will likely come from product development in new indications, such as EGFR-inhibitor associated skin rash. However, given the early-phase of clinical development for such products, it will be some time before any impact is made and true future potential can be determined.
Reasons to Purchase
Understand market specific drivers and predict the future potential of key marketed and pipeline oncology supportive care products Assess the impact of product launches and identify the opportunities and risks for key products within the oncology supportive care market Adopt knowledge to drive strategic planning for marketed products and optimize the market penetration of new entrants
ABOUT DATAMONITOR HEALTHCARE 2
About the Oncology pharmaceutical analysis team 2
Andrew Paramore - Oncology Lead Analyst & Head of Product Development 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Objective of the analysis 3
Datamonitor insight into the oncology supportive care market 3
Related reports 5
Upcoming reports 5
CHAPTER 2 PIPELINE OVERVIEW 7
Pipeline overview 7
Pipeline by developmental phase and indication 9
The oncology supportive care pipeline in its entirety is relatively sparse 9
Pipeline split by phase 11
The late-phase pipeline will flourish in the future, as early-stage agents move forward in development 12
Pipeline split by indication 12
Chemotherapy-induced nausea and vomiting is the most popular indication in terms of pipeline activity 13
Significant unmet needs in the cancer-related mucositis market means the early-phase pipeline has increased in activity 13
A greater level of activity would have been expected in the cancer-related thrombocytopenia pipeline 13
Pipeline by company 14
At least 67 companies are involved in the oncology supportive care pipeline 14
The high involvement of smaller companies in the oncology supportive care pipeline is not surprising, given that 82% of compounds are in early-phase development 14
The top three companies in terms of marketed and pipeline oncology supportive care products are Amgen, GlaxoSmithKline and Roche 15
Amgen 15
GlaxoSmithKline 16
Roche 18
Key metrics 20
Datamonitor pipeline assessment summary 23
CHAPTER 3 MARKET DEFINITION AND PIPELINE DYNAMICS 29
Supportive care overview 29
Market definition and classification of products 30
A4A - Anti-emetics and anti-nauseants 30
Playing a key role in the prophylaxis and/or treatment of acute and delayed chemotherapy-induced nausea and vomiting 30
Defining the emetic risk of various cytotoxics used to treat cancer 31
Anti-emetic mode of action is conferred by blocking the action of various neuroreceptors 31
Classes of anti-emetic/anti-nauseant 32
B3C - Erythropoiesis-stimulating products 35
Anemia may severely affect patient quality of life 35
Products capable of stimulating the production of red blood cells can be used to treat cancer-related anemia 35
Key erythropoiesis-stimulating products 35
L3A1 - Colony-stimulating factors 36
Neutropenia was potentially fatal before the introduction of current supportive care measures 36
Colony-stimulating factors promote the production of white blood cells to prevent neutropenia 36
Key colony-stimulatings factors 37
L3A9 - All other immunostimulating agents excluding interferons 37
Thrombocytopenia increases the risk of severe bleeding in cancer patients 37
Only one formally approved agent exists for the prevention of thrombocytopenia to date 38
M5B1/M5B2 - Bisphosphonate bone calcium regulators 38
Bone metastases and tumor-induced hypercalcemia can cause significant morbidity in cancer patients 38
Bisphosphonates are used in the prevention and/or treatment of cancer-related skeletal events due to their ability to restore normal balance to bone activity 39
Key bisphosphonates approved for oncology indications 39
V3D0 - Detoxifying agents for antineoplastic treatment 40
Mucositis can result in significant complications, exacerbated by further cancer treatment and any therapy-related nausea and vomiting 40
Use of the only growth factor approved for mucositis to date is restricted by its cost, particularly in more conservative markets 41
Current market dynamics 41
A top-line view of the oncology supportive care market 41
The large majority of drug classes underwent significant sales growth between 2005 and 2006 41
The oncology supportive care market by drug class 42
Epidemiology 45
Epidemiology of cancer 45
A continuously expanding patient base 45
Increased incidence a consequence of aging populations and lifestyle modifications 45
Epidemiology of supportive care indications 47
CHAPTER 4 MARKETED PRODUCTS FORECAST ANALYSIS 49
Country-specific assumptions and effects 49
Generic pricing and erosion assumptions 49
Product assumptions and effects 49
A4A1 - 5-HT3 serotonin receptor antagonists 49
Drug class asumptions 49
Helsinn Pharma/MGI Pharma's Aloxi (palonosetron) 50
Sanofi-Aventis's Anzemet (dolasetron) 53
Roche/Chugai's Kytril (granisetron) 54
Astellas' Nasea (ramosetron) 55
Novartis's Navoban (tropisetron) 56
Welfide/Japan Tobacco's Serotone (azasetron) 56
Nisshin Kyorin Pharmaceuticals' Sinseron (indisetron) 57
GlaxoSmithKline's Zofran (ondansetron) 57
A4A9 - Other anti-emetics/anti-nauseants 58
Merck & Co's Emend (aprepitant) 58
B3C0 - Erythropoiesis-stimulating products 64
Drug class assumptions 64
Controversy affecting the drug class as a whole 64
Amgen's Aranesp (darbepoetin alfa) 71
Amgen Epogen/Johnson & Johnson's Procrit/Kirin's Eprex (epoetin alfa) 74
Roche's NeoRecormon (epoetin beta) 76
L3A1 - Colony-stimulating factors 78
Chugai's Granocyte (lenograstim) 78
Bayer Schering/Berlex's Leukine (sargramostim) 80
Amgen's Neulasta (pegfilgrastim) 81
Amgen's Neupogen (filgrastim) 83
Kyowa Hakko Kogyo's Neu-Up (nartograstim) 85
L3A9 - Other immunostimulating agents 85
Wyeth's Neumega (oprelvekin) 85
M5B1/M5B2 - Oral and injectable bisphosphonates 88
Drug class assumptions 88
Proctor & Gamble/Sanofi-Aventis's Actonel (risedronic acid) 88
Novartis's Aredia (pamidronic acid) 90
Astellas' Bisphonal (incadronic acid) 91
Roche/GlaxoSmithKline's Bondronat/Boniva/Bonviva (ibandronic acid) 92
Bayer Schering's Bonefos (clodronic acid) 96
Novartis's Zometa (zoledronic acid) 97
V3D0 - Other detoxifying agents for cancer 100
Amgen's Kepivance (palifermin) 100
Forecasts 102
Forecast methodology 102
CHAPTER 5 PIPELINE ANTI-EMETIC PRODUCTS ANALYSIS AND FORECASTS 103
Pipeline overview 103
Definition of current comparator 104
GlaxoSmithKline's Zofran (ondansetron) 104
The preferred 5-HT3 receptor antagonist in the seven major markets 104
Reckitt Benckiser Healthcare/BioDelivery Sciences' Emezine (reformulated prochlorperazine maleate) 105
Drug profile 105
Issue of a non-approvable letter by the FDA for Emezine may not bode well for the drug's future 105
Clinical trial data 106
Pharmacokinetic studies indicate that Emezine's route of administration may result in a higher plasma concentration than traditional formulations 106
Datamonitor comments 106
BioDelivery Sciences believes Emezine to confer advantages by virtue of its formulation 106
The widespread availability of generic prochlorperazine and more efficacious newer anti-emetics means that uptake of Emezine may be limited 107
Hana Biosciences/NovaDel Pharma's Zensana (reformulated ondansetron) 108
Drug profile 108
Long-term stability issues means reformulation of Zensana was necessary, however, this has delayed commercialization 108
Clinical trial data 108
Zensana has been proven bioequivalent to Zofran 108
Surveyed members of the oncology community ranked Zensana highly in terms of potential ease of use 109
Datamonitor comments 110
Zensana confers administration advantages over traditionally formulated ondansetron, however, the drug's price point should be set with caution 110
ProStrakan's Sancuso (reformulated granisetron) 111
Drug profile 111
Sancuso allows for an alternative route of administration to Kytril 111
Clinical trial data 111
Phase III data show Sancuso to confer comparable efficacy and safety to oral Kytril 111
Datamonitor comments 112
Sancuso must be priced competitively in order to avoid being driven out of the market by generic versions of 5-HT3 anatagonists 112
AP Pharma's APF-530 (reformulated slow-release granisetron) 113
Drug profile 113
Slow-release formulation of granisetron should provide consisent protection against chemotherapy-induced nausea and vomiting 113
Clinical trial data 114
Clinical data support the use of a single injection of APF-530 adminstered 30 minutes before chemotherapy to provide continuous protection 114
Datamonitor comments 115
While generic versions of granisetron will see uptake, APF-530 may lose out somewhat to Sancuso due to its formulation 115
GlaxoSmithKline's casopitant (GW-679769) 115
Drug profile 115
Casopitant could become the second NK-1 antagonist to reach the market 115
Clinical trial data 116
Casopitant in combination with Zofran is effective in patients receiving moderately-emetogenic chemotherapy 116
Varying doses of capositant are effective in preventing nausea and vomiting associated with highly-emetogenic chemotherapy 118
Datamonitor comments 120
Given the youth of the NK-1 antagonist drug class, casopitant could represent a valuable addition to treatment options 120
Forecasts 122
Datamonitor drug assessment summary 124
Future potential of pipeline anti-emetic products 125
The pipeline anti-emetics will enjoy reasonable uptake and sales, however, no major breakthroughs in the prevention and/or treatment of chemotherapy-induced nausea and vomiting will be provided 125
CHAPTER 6 PIPELINE ERYTHROPOIESIS-STIMULATING PRODUCTS ANALYSIS AND FORECASTS 126
Pipeline overview 126
Definition of current comparator 127
Amgen's Aranesp (darbepoetin alfa) 127
Available across most of the seven major markets and a more convenient dosing schedule for patients 127
Shire's Dynepo (epoetin delta) 127
Drug profile 127
The first recombinant erythropoietin to be produced in human cells 127
Clinical trial data 128
A complete dearth of information relating to Dynepo's development in cancer-related anemia... 128
...however, equal efficacy to Epogen/Procrit has been demonstrated in treatment of anemia related to chronic kidney disease 128
Datamonitor comments 129
Ongoing patent litigation with Amgen resulted in delayed European launch of Dynepo, plus a ban on US launch until relevant patents have expired 129
Dynepo's pricing at a 30% discount to its competitors in Germany means that some off-label use in oncology indications is likely 129
Roche's Mircera (continuous erythropoietin receptor activator) 130
Drug profile 130
A novel erythropoiesis-stimulating agent with several theoretical advantages over competitors 130
Suspension of recruitment into an oncology Phase II due to an imbalance in fatalities across treatment arms 131
Clinical trial data 132
Mircera appears to have dose-dependent clinical activity in anemic NHL patients receiving chemotherapy 132
Phase II results in NSCLC patients support the feasibility of extended administration of Mircera 133
Mircera produces a rapid and sustained hemoglobin response in multiple myeloma patients 134
Datamonitor comments 134
Despite potentially negative publicity surrounding suspension of enrollment into the NH19960 study, Mircera's reputation should remain relatively intact 134
Hurdles put in place by Amgen need to be overcome 135
Entering the EU market is likely to be slightly easier for Roche 135
The entire erythropoietin drug class has come under fire 136
Forecasts 137
Datamonitor drug assessment summary 138
Future potential of pipeline erythropoeisis-stimulating products 139
Both pipeline erythropoietins are expected to see some off-label use prior to formal approval in oncology indications 139
CHAPTER 7 PIPELINE ANTI-NEUTROPENIA PRODUCTS ANALYSIS AND FORECASTS 141
Pipeline overview 141
The current cancer-related neutropenia pipeline 141
An exceedingly sparse pipeline means any threat to currently marketed products is minimal 141
CHAPTER 8 PIPELINE ANTI-THROMBOCYTOPENIA PRODUCTS ANALYSIS AND FORECASTS 142
Pipeline overview 142
Definition of current comparator 143
Wyeth's Neumega (oprelvekin) 143
Chosen only due to the complete lack of other commercially approved products in this indication 143
GlaxoSmithKline/Ligand Pharmaceuticals' Promacta (eltrombopag) 143
Drug profile 143
Promacta's oral availability may represent a significant advantage 143
Clinical trial data 144
Early trial data demonstrates Promacta's ability to boost platelet levels in cancer patients undergoing chemotherapy, but fails to meet primary endpoint 144
Positive Phase III data in other indications mean that theoretically, Promacta should confer efficacy in cancer-related thrombocytopenia 144
Datamonitor comments 145
A severe lack of approved agents for the prevention and/or treatment of cancer-related thrombocytopenia provides opportunity 145
A gap in the market exists for a product such as Promacta, which GlaxoSmithKline should take full advantage of 146
Amgen's AMG-531 146
Drug profile 146
A novel drug designed to specifically target the thrombopoietin receptor 146
Clinical trial data 147
No cancer-specific study data exist, making it difficult to judge AMG-531's potential in this patient population 147
Datamonitor comments 148
Amgen's leading status in the oncology supportive care market will prove invaluable for AMG-531 148
Forecasts 149
Datamonitor drug assessment summary 150
Future potential of pipeline anti-thrombocytopenia products 151
Following initial off-label use in oncology indications, the anti-thrombocytopenia pipeline products are forecast to enjoy significant sales 151
CHAPTER 9 PIPELINE ANTI-MUCOSITIS PRODUCTS ANALYSIS AND FORECASTS 153
Pipeline overview 153
Definition of current comparator 154
Amgen's Kepivance (palifermin) 154
Chosen only due to the complete lack of other commercially approved products in this indication 154
MGI Pharma's Saforis (L-glutamine) 154
Drug profile 154
Increasing availability of L-glutamine in the oral mucosa may prevent the onset of mucositis 154
Clinical trial data 155
Phase III trial results showing Saforis is capable of significantly reducing the incidence of oral mucositis forms the basis for NDA submission 155
Earlier Phase III results show Saforis appears to reduce the incidence of oral mucositis 156
Datamonitor comments 156
Cost and route of administration of Amgen's Kepivance places Saforis at a significant advantage 156
Forecasts 157
Datamonitor drug assessment summary 158
Future potential of pipeline anti-mucositis products 159
A relatively low level of peak sales are deceptive in the face of reasonable uptake of Saforis in cancer-releated mucositis 159
CHAPTER 10 PIPELINE CANCER-RELATED SKELETAL EVENTS PRODUCTS ANALYSIS AND FORECASTS 161
Pipeline overview 161
Definition of current comparator 162
Novartis's Zometa (zoledronate) 162
The leading bisphosphonate for the prevention and/or treatment of cancer-related skeletal events 162
Amgen's denosumab (AMG-162) 162
Drug profile 162
The first targeted therapy for cancer-related skeletal events 162
Clinical trial data 164
Interim results show denosumab to be at least as effective as intravenous bisphosphonates in reducing the risk of cancer-related skeletal events 164
Interim results show denosumab normalizes bone turnover more frequently than intravenous bisphosphonates 165
Datamonitor comments 166
By virtue of its monoclonal antibody formulation, denosumab is likely to be more expensive than currently marketed bisphosphonates... 166
...however, its lack of association with osteonecrosis of the jaw may work in its favor 166
Amgen's experience represents a major advantage for denosumab 167
Forecasts 167
Datamonitor drug assessment summary 168
Future potential of pipeline cancer-related skeletal events products 169
Denosumab theoretically confers several advantages over currently available bisphosphonates, therefore uptake and accompanying sales are forecast to be encouraging 169
CHAPTER 11 COMMERCIAL IMPACT AND LIFECYCLE MANAGEMENT: CASE STUDY 171
The changing oncology supportive care market 171
Current areas of commercial opportunity 171
Several areas of supportive care are drastically underserved at present 171
Potentially increasing range of use for current products 172
Increasing use of targeted therapies 173
A shift towards increased use of molecular targeted therapies will introduce new supportive care challenges 173
New supportive care measures need to be developed, thereby providing significant commercial opportunity... 174
...yet, it could be that the high cost of the targeted therapies will result in hampered uptake of supportive care products 175
The threat of biosimilars 176
The biologic supportive care products will no longer be protected from generic competition 176
Some biosimilar products can be launched in the EU immediately... 176
...however, the US is lagging behind 176
The high cost of some supportive care products inhibits their use, indicating a great desire for cheaper biosimilar versions... 177
...although biosimilar drugs bring with them a new set of issues 177
Increased safety concerns in future 177
As seen with the erythropoeitins class, increased vigilance with respect to safety may be enforced in the future 177
How the oncology supportive care market will change 178
On the whole, the oncology supportive care market will undergo positive growth... 178
...albeit at a minimal growth rate, due to a lack of major innovation 179
Future growth is likely to come from those early-phase products targeting new supportive care indications 180
APPENDIX A - MARKET DATA AND MAJOR BRAND KEY FACTS 181
A4A (anti-emetics and anti-nauseants) class market data 181
B3C (erythropoiesis-stimulating products) class market data 184
L3A1 (colony-stimulating factors) class market data 186
L3A9 (other immunostimulating agents) class market data 188
M5B1/M5B2 (oral and injectable bisphosphonates) class market data 189
V3D0 (other detoxifying agents for cancer) class market data 191
Sales data and forecasts 191
PowerPoint Executive Presentation 192
APPENDIX B - SALES FORECASTS 193
US forecasts 193
Japan forecasts 196
France forecasts 199
Germany forecasts 202
Italy forecasts 205
Spain forecasts 208
UK forecasts 211
Five major European markets (EU5) forecasts 214
Seven major market forecasts 217
APPENDIX C 221
Bibliography 221
List of tables 233
List of figures 234
Methodology 235
Datamonitor forecast methodology 235
Forecasts for marketed drugs 235
Forecasts for pipeline drugs 236
Datamonitor drug assessment methodology 237
About Datamonitor 239
About Datamonitor Healthcare 239
About the Oncology analysis team 240
Disclaimer 241
