Executive Summary
Two Stones to Kill One Bird? Combination Therapies Could be the Future of Cancer Treatment.
In the ongoing battle against cancer, the medical community is looking to promising multi-targeted therapies for more effective and enduring treatments, says a new report by pharmaceutical industry observers GBI Research.
According to the report, there is a wave of combination therapies in late stage development that have the potential to revolutionize long-term oncological treatment by addressing the complexities of cancer growth.
In Silico methods (the use of computer simulations) have been instrumental in the generation of biological and chemical data on ligands and targets. These same methods are now being employed to identify and design multi-target compounds, facilitated by the wealth of bioactivity information advanced computer simulations provide.
GBI Research's intelligence shows that lung cancer treatments represent the greatest share of the Phase III combination therapy development pool with 16%. This relatively high percentage is not surprising considering the disease's growing prevalence around the world due to an increase in tobacco consumption in emerging economies such as China. The second and third most populous combination therapies in Phase III were breast cancer and colorectal cancer, with 13.4% and 8.5%, respectively.
There are, however, regulatory problems regarding the co-development of novel drugs. The primary concern is that this process will inevitably provide less information about the safety and effectiveness of these agents than if they were developed and tested individually.
The FDA has drafted guidance and recommendations on how combination therapies should be processed, including a proposal that drugs should only be developed in combination when there is a compelling biological rationale for the use of the combination, or where the drugs cannot be developed individually (if this were lead to drug resistance, for example).
Combinations also need to be shown in preliminary clinical studies to provide greater-than-additive activity or a more durable response compared to using the agents alone.
Multi-Targeted Therapies - New Wave of Combination Therapies in Late Stage Development for Lung Cancer Offer Promise
This report provides an overview of the discovery and development of therapeutic drug combinations and multi-target drugs for oncology.
This report was built using data and information sourced from proprietary databases, primary and secondary research, and in-house analysis conducted by GBI Research's team of industry experts.
Abstract
Multi-Targeted Therapies - New Wave of Combination Therapies in Late Stage Development for Lung Cancer Offer Promise
Summary
GBI Research, the leading business intelligence provider, has released its latest research, "Multi-Targeted Therapies - New Wave of Combination Therapies in Late Stage Development for Lung Cancer Offer Promise", which provides an overview of the discovery and development of therapeutic drug combinations and multi-target drugs for oncology. The report is built using data and information sourced from proprietary databases, primary and secondary research and in-house analysis by GBI Research's team of industry experts. The report provides an insight into different methods and techniques used to identify and design drugs that act upon multiple targets in the treatment of cancer. It also focuses on the design and development of combination therapies to address multiple targets in oncology and the challenges surrounding this.
Pipeline analysis of the Phase III oncology pipeline focuses on indications such a lung cancer, breast cancer, colorectal cancer, prostate cancer, ovarian cancer, leukemia, lymphoma, head and neck cancer and multiple myeloma. The most common types of drug combinations used to treat these indications are highlighted and promising molecules in each indication have been identified.
Scope
- An introduction to network biology and its implications in the design of drugs and cancer therapy.
- The rationale behind the use of multi-target drugs or combination therapy to address multiple targets in cancer treatments.
- A comparison of the strengths and weaknesses in the multi-target approach to the use of drug combinations.
- Methods and techniques for the discovery and design of multi-target drugs.
- Methods for designing combination therapies for cancer and the challenges involved in the process.
- Late-stage pipeline analysis of combination therapies in oncology in indications such as lung cancer, breast cancer, colorectal cancer, prostate cancer and ovarian cancer.
Reasons to buy
- Develop business strategies by understanding the trends shaping and driving research in the field of multi-target therapies.
- Understand the processes being used to design and develop multi-target drugs and combination therapies and identify some of the challenges involved in this.
- Identify key molecules in development being used in combination based on indication.
- Reinforce R&D pipelines by identifying common drug class combinations in the pipeline for different cancer indications.
TOC
1 Table of Contents
1 Table of Contents 4
- 1.1 List of Tables 5
- 1.2 List of Figures 5
2 Multi-Targeted Therapies - Overview 6
- 2.1 Introduction 6
- 2.1.1 Biological Networks 6
- 2.1.2 History of Multi-component Drugs 8
- 2.1.3 Types of Multi-Targeted Therapy 8
- 2.1.4 Many Small Molecule Drugs are Promiscuous 9
- 2.1.5 Off-target Effects and Drug Repositioning 9
- 2.2 Promiscuous Drugs versus Combination Therapies 10
3 Designing Multi-Target Drugs 11
- 3.1 Lead Generation Approaches 11
- 3.1.1 Knowledge-based Approaches 11
- 3.1.2 Screening 12
- 3.1.3 Fragment-based Approach 12
- 3.1.4 In Silico Screening Methods 12
- 3.1.5 Conclusions 13
- 3.1.6 Challenges of Lead Optimization 14
- 3.2 Multi-Target Protein Kinase Inhibitors 14
- 3.2.1 Early Marketed Kinase Inhibitors 14
- 3.2.2 Newer Designed Multi-kinase Inhibitors 15
- 3.2.3 Oncogene Addiction 15
- 3.2.4 Overcoming Resistance 15
4 Designing Combination Therapies 16
- 4.1 Which Products to Combine? 16
- 4.1.1 Cell-based Phenotypic Assays 16
- 4.1.2 Synthetic Lethality 16
- 4.2 Designing Dual Novel Drug Combinations 17
- 4.3 Challenges for Development and Design of Combination Drugs 18
- 4.3.1 Combined Toxicity 18
- 4.3.2 FDA Guidelines for Development of Drugs for Use in Combination 18
- 4.3.3 Clinical Trial Design 20
- 4.3.4 Developing Drugs in Collaboration 21
5 Pipeline Analysis of Late Stage Oncology Combination Therapies 22
- 5.1 Phase III Oncology Pipeline by Number of Drugs in Combination 22
- 5.2 Phase III Oncology Pipeline by Indication 23
- 5.2.1 Overall 24
- 5.2.2 Lung Cancer 26
- 5.2.3 Breast Cancer 29
- 5.2.4 Colorectal Cancer 31
- 5.2.5 Lymphoma 33
- 5.2.6 Multiple Myeloma 35
- 5.2.7 Ovarian Cancer 37
- 5.2.8 Prostate Cancer 39
- 5.2.9 Leukemia 41
- 5.2.10 Head and Neck Cancer 43
- 5.2.11 Squamous Cell Carcinoma 45
- 5.2.12 Other Oncology Indications 47
6 Appendix 53
- 6.1 Abbreviations 53
- 6.2 Sources 53
- 6.3 Research Methodology 54
- 6.3.1 Secondary Research 54
- 6.3.2 Primary Research 54
- 6.3.3 Expert Panel Validation 55
- 6.4 Contact Us 55
- 6.5 Disclaimer 55
List of Tables
1.1 List of Tables
- Table 1: Clinical Trial Design Considerations for Three Typical Scenarios Combining Drug A and Drug B 20
- Table 2: Combination Therapies in Oncology, Phase III Pipeline by Number of Drugs in Combination. 2012 23
- Table 3: Combination Therapies in Oncology, Phase III Pipeline by Indication, 2012 24
- Table 4: Phase III Pipeline Combinations in Lung Cancer 27
- Table 5: Phase III Pipeline Combinations in Breast Cancer 30
- Table 6: Phase III Pipeline Combinations in Colorectal Cancer 32
- Table 7: Phase III Pipeline Combinations in Lymphoma 34
- Table 8: Phase III Pipeline Combinations in Multiple Myeloma 36
- Table 9: Phase III Pipeline Combinations in Ovarian Cancer 38
- Table 10: Phase III Pipeline Combinations in Prostate Cancer 40
- Table 11: Phase III Pipeline Combinations in Leukemia 42
- Table 12: Phase III Pipeline Combinations in Head and Neck Cancer 44
- Table 13: Phase III Pipeline Combinations in Squamous Cell Carcinoma 46
- Table 14: Phase III Pipeline Combinations in Remaining Oncology Indications 49
List of Figures
1.2 List of Figures
- Figure 1: Three Different Approaches to Multi-Target Therapy 8
- Figure 2: Determining if Co-development is an Appropriate Development Option 19
- Figure 3: Combination Therapies in Oncology, Phase III Pipeline by Number of Drugs in Combination, 2012 22
- Figure 4: Combination Therapies in Oncology, Phase III Pipeline by Indication, 2012 24
- Figure 5: Multi-Targeted Therapies, Drug Category and Color Used for Analysis 25
- Figure 6: Multi-Targeted Therapies, Phase III Pipeline Combinations in Lung Cancer, 2012 26
- Figure 7: Multi-Targeted Therapies, Phase III Pipeline Combinations in Breast Cancer, 2012 29
- Figure 8: Multi-Targeted Therapies, Phase III Pipeline Combinations in Colorectal Cancer, 2012 31
- Figure 9: Multi-Targeted Therapies, Phase III Pipeline Combinations in Lymphoma, 2012 33
- Figure 10: Multi-Targeted Therapies, Phase III Pipeline Combinations in Multiple Myeloma, 2012 35
- Figure 11: Multi-Targeted Therapies, Phase III Pipeline Combinations in Ovarian Cancer, 2012 37
- Figure 12: Multi-Targeted Therapies, Phase III Pipeline Combinations in Prostate Cancer, 2012 39
- Figure 13: Multi-Targeted Therapies, Phase III Pipeline Combinations in Leukemia, 2012 41
- Figure 14: Multi-Targeted Therapies, Phase III Pipeline Combinations in Head and Neck Cancer, 2012 43
- Figure 15: Multi-Targeted Therapies, Phase III Pipeline Combinations in Squamous Cell Carcinoma, 2012 45
- Figure 16: Color Map Showing Phase III Pipeline Combinations in Remaining Oncology Indications, 2012 47
- Figure 17 : Color Map Showing Phase III Pipeline Combinations in Remaining Oncology Indications, 2012 (cont) 48
