Stakeholder Opinions: Gene Therapy - Gene therapy to deliver after 20 years of clinical development

Introduction

Gene therapy looks to be coming of age, with seven projects in Phase III clinical development and one project currently under regulatory review. A shift in development from pure gene replacement to using gene therapy as a therapeutic delivery tool has enhanced the technology's commercial potential over the last 10 years.

Scope

• In-depth analysis of the current gene therapy clinical pipeline.
• Analysis of key target indications for gene therapies and key companies active in the filed.
• Key opinion leader review of technologies driving clinical gene therapy.
• Identification of drivers and inhibitors to the commercial success of gene therapy.

Highlights

Most of the indications being targeted in the current gene therapy pipeline are multifactorial rather than monogenic in etiology. Reflecting this trend, cancer has become the leading therapy area for gene therapy development, constituting nearly half of the clinical projects under development.

The development of highly engineered recombinant viruses has increased the safety of gene therapy. As clinical evidence for the enhanced safety of these vectors gathers over the next few years, the perceived risk/reward profile for gene therapy will change in some disease areas.

With endless lucrative targets for companies developing safe and efficient delivery of genes, the commercial potential of gene therapy remains high.

Reasons to Purchase

• Quantify the gene therapy pipeline.
• Assess the changing vectors and target indications for gene therapy.
• Identify the leading companies involved in gene therapy development.

Overview 1

• Catalyst 1
• Summary 1

About Datamonitor healthcare 2

About the healthcare research & analysis team 2

• Executive Summary 3
• Scope of the analysis 3
• Datamonitor insight into the gene therapy market 3
• Related reports 4
• Upcoming reports 4
• Table of Contents 5

1. Market Overview 6

• Key findings 6
• Market definition for this report 7
  
  • Clinical trial trends 1989-2009 7
  • A timeline of clinical gene therapy 7
  • Geographic distribution of gene therapy clinical trials, 1989-2009 11
• Current market 12
  
  • Gendicine (SiBiono, a subsidiary of Benda Pharmaceuticals, China) 12
  • Factors leading Gendicine to become the first commercially available gene therapy 13
  • Commercial success of Gendicine 13
  • Clinical efficacy 14
  • Safety of Gendicine 15
  • Lessons from Gendicine 16
  • Rexin-G (Epeius Biotechnologies, Philippines) 16
• Current pipeline 16
  
  • Phase III and pre-approval projects 17
  • Collategene (AnGes and Daiichi Sankyo) 18
  • Glybera (Amsterdam Molecular Therapeutics) 18
  • Cerepro (Ark Therapeutics) 19
  • Generx (Cardium Therapeutics) 19
  • TNFerade (GenVec) 20
  • TK007 (MolMed) 20
  • XRP0038 (Sanofi-Aventis) 20
  • Allovectin-7 (Vical) 21
  • Broad applicability across disease types 22
  • Key therapy areas 23
  • Most frequently targeted indications 25
  • Cancer 26
  • Cancer types targeted by gene therapy 27
  • Pancreatic cancer 29
  • Head and neck cancer 30
  • Breast cancer 31
  • Prostate cancer 32
  • Central nervous system 32
  • Parkinson's disease 33
  • Leber congenital amaurosis (retinal disorder) 35
  • Multi-indication potential of nerve growth factor 35
  • Cardiovascular and circulatory system 36
  • Peripheral arterial disease 37
  • Key companies 39
• 2. Technology Review 41
• Key findings 41
• Gene therapy methods 42
  
  • Ex vivo gene therapy 42
  • In vivo gene therapy 43
• Delivery of genes 43
  
  • Different delivery mechanisms for different situations 45
  • Viral vectors 46
  • Movement towards adeno-associated viruses vectors 47
  • Adenovirus 49
  • Retrovirus 50
  • Adeno-associated viruses 53
  • Mechanical delivery 56
• Gene regulation 58
  
  • Regulatable vectors 58
• 3. Commercial Considerations 60
• Key findings 60
• Key drivers to commercial success 61
  
  • Endless lucrative targets for companies mastering delivery 61
  • Access to previously untapped markets 61
• Key inhibitors to commercial success 62
  
  • Safety 62
  • Immune response 63
  • Mutagenesis 64
  • Germline transmission 64
  • Funding and Big Pharma involvement 64
  • Academic funding 64
  • Big Pharma involvement 65
  • Reliable delivery and regulatable expression 67
  • Challenging to treat multifactorial diseases 68
  • Access to vectors 68
  • Stigma associated with gene therapy 69
• Market entry strategies 69
• Pricing 71
• Regulation 72
  
  • US 72
  • FDA - Center for Biologics Evaluation and Research (CBER) 72
  • NIH - Recombinant DNA Advisory Committee (RAC) 73
  • Europe 73
  • European Medicines Agency (EMEA) 73
  • Germany 74
  • UK 74
  • France 74

Bibliography 76

• Journals 76
• Websites 78
• Datamonitor reports 80

Appendix A 82

• Raw data 82

Appendix B 86

• Contributing experts 86
• Report methodology 86
• About Datamonitor 87
• About Datamonitor Healthcare 87
• About the healthcare research & analysis team 88
• Disclaimer 90

List of Tables

• Table 1: Gendicine efficacy in head and neck squamous cell carcinoma 15
• Table 2: Gendicine follow-up survival data in head and neck squamous cell carcinoma 15
• Table 3: Phase III and pre-approval gene therapy projects, 2009 18
• Table 4: Gene therapy methods for the treatment of cancer 27
• Table 5: Gene therapies in development for pancreatic cancer, 2009 29
• Table 6: Gene therapies in development for head and neck cancer, 2009 30
• Table 7: Gene therapies in development for breast cancer, 2009 31
• Table 8: Gene therapies in development for prostate cancer, 2009 32
• Table 9: Gene therapies in development for Parkinson's disease, 2009 34
• Table 10: Gene therapies in development for Leber congenital amaurosis (retinal disorder), 2009 35
• Table 11: Gene therapies in development for peripheral arterial disease, 2009 38
• Table 12: Vector system properties 46
• Table 13: Advantages and disadvantages of the adenoviral vector in gene therapy 49
• Table 14: Advantages and disadvantages of the lentiviral vector in gene therapy 51
• Table 15: Advantages and disadvantages of the adeno-associated viral (AAV) vector in gene therapy 53
• Table 16: Clinical programs in development using gene therapy, 2009 83

List of Figures

• Figure 1: Timeline of gene therapy clinical development 10
• Figure 2: Number of gene therapy clinical trials approved worldwide, 1989-2008 11
• Figure 3: Geographic distribution of gene therapy clinical trials, 1989-March 2009 12
• Figure 4: Number of clinical trials for gene therapy at each stage of development, 2009 17
• Figure 5: Phase II results investigating high-dose Allovectin-7 in recurrent or unresponsive Stage III/IV melanoma 21
• Figure 6: Number of gene therapy clinical projects underway for each therapy area, 2009 23
• Figure 7: Number of genes in clinical trials for each therapy area, 2009 24
• Figure 8: Number of gene therapy clinical projects underway by stage for key therapy areas, 2009 25
• Figure 9: Indications with three or more clinical projects in development, 2009 26
• Figure 10: Number and stage of development for cancer gene therapy programs, 2009 28
• Figure 11: Number and stage of development for CNS gene therapy programs, 2009 33
• Figure 12: Number and stage of development for cardiovascular and circulatory system gene therapy projects, 2009 37
• Figure 13: Key companies with gene products in clinical development, 2009 40
• Figure 14: In vivo versus ex vivo gene therapy 42
• Figure 15: Vectors used in gene therapy clinical trials, 1989-March 2009 44
• Figure 16: Vectors used in gene therapy clinical trials, 2009 45
• Figure 17: A typical virus replication cycle 47
• Figure 18: Virus types used as gene therapy vectors in clinical trials, 1989-March 2009 48
• Figure 19: Virus types used as gene therapy vectors in clinical trials, 2009 49