Stakeholder Opinions: Biologics in Infectious Diseases Well defined target populations are key to commercial success

Antibody-based agents represent a novel approach to the treatment and prophylaxis of infectious diseases. In recent years, considerable interest has been expressed in their further development, driven by advances in technology that improve manufacturing cost and tolerability: fully human antibody reagents avoid the toxicities associated with traditional human- or animal-derived serum therapy.



Report Highlights
Antibodies offer several advantages over conventional anti-infectives and vaccines but their cost and mode of administration limits their use in certain areas. A high unmet need and defined target groups are required to gain commercial success. Pipeline products fulfilling these criteria have a greater chance of commercial and scientific success. Accounting for the majority of nosocomial infections, MRSA is the most popular target for antibody development. Despite concerns over resistance there are still several antibiotics that can treat multi-drug resistant S.aureus, reducing the need for antibody-based therapeutics. The greater need lies in treatment of Pseudomonas and fungal infections. For most viral infections, conventional therapies are able to control disease progression effectively. In HIV and HCV the real need is for a cure or preventative measure but the majority of pipeline products are being developed for treatment of these infections.


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ABOUT DATAMONITOR HEALTHCARE 2
About the Infectious Diseases and Respiratory pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into biologics infectious diseases 3
Contributing experts 6
Related reports 6
Upcoming related reports 7
CHAPTER 2 COMMERCIAL OUTLOOK 9
Unmet needs 9
Development issues 10
Difficulties in identification of antigenic targets 11
Competitive pressure from vaccines and conventional anti-infectives 12
Strategy for antibody use 12
Prophylaxis 12
Treatment 14
Vaccine use will be in patients with sufficient time to mount an immune response 16
CHAPTER 3 BIOLOGICS TECHNOLOGY OVERVIEW 19
Biologics comprise of a range of products 19
Therapeutic proteins 19
Vaccines 19
Monoclonal antibodies 20
Antibody structure and role in immune response 20
Production of monoclonal antibodies 22
Newer production methods 26
Mammalian cell culture is the most widely used system 27
Emerging technologies 28
Antibody fragments 28
Polyclonal antibodies 29
Antibody mechanism of action and target identification for infectious disease 30
Monoclonal antibodies as anti-infective agents 30
Potential advantages of MAb therapy 32
Potential disadvantages of MAb therapy 33
CHAPTER 4 ANTIVIRALS 34
Respiratory syncytial virus (RSV) 34
Disease background 34
Etiology and targets for drug development 35
Lack of effective antivirals or a vaccine has created an opportunity for prophylactic agents 38
Antibody-based prophylaxis dominates the market 40
Despite Synagis' success there are relatively few MAbs in late-stage development for RSV 42
Motavizumab 43
HIV 44
Disease background 44
Current treatment options 45
HIV etiology and drug targets 45
Neutralizing antibodies targeting the virus and infected cells 47
MAbs targeting the uninfected cell 49
Pipeline overview of HIV anti-cell MAbs in development 50
TNX-355 50
PRO-140 51
HGS004 52
Where do MAbs fit into HAART? 53
Hepatitis C 54
Disease background 54
Targets for antibody development and pipeline overview 55
XTL-6865 58
Bavituximab 59
HuMax-HepC 59
IB-657 60
Other viral infections 60
Rabies 60
West Nile virus 62
SARS 63
CHAPTER 5 ANTIBACTERIALS 65
Resistance to current antibiotics driving the investigation of novel approaches 65
MRSA most popular target for antibody development but the real need is for new gram-negative therapies 67
Bacterial targets for antibody development 68
Staphylococci 69
Several antibiotics are addressing the issue of resistance reducing the need for novel approaches 70
Patient groups that would potentially benefit from anti-staph antibody-based therapy 71
Potential targets and products in development 72
Protein A may limit effectiveness of immunotherapeutic approaches 73
Majority of pipeline products aimed at MRSA infections 73
Aurograb 74
BSYX-A110 75
Aurexis 76
ETI-211 77
Enterococci 78
The elderly are most at risk from enterococcal infections 79
Most pipeline products are in very early stages of development 81
Clostridium difficile 82
Increase in Clostridium difficile-associated disease attributed to hypervirulent strain 82
Immunological approaches to treatment could cut reliance on antibiotics, restoring the patient's commensal flora 84
Pipeline overview 85
MDX-066 + MDX1388 85
NTCD 86
Pseudomonas aeruginosa 86
Lack of novel antibiotics targeting multi-drug resistant strains indicates a high unmet need 88
Pipeline overview 89
KB001 89
KPB101 90
Bacillus anthracis 90
Abthrax (raxibacumab) 92
Valortim (MDX-1303) 93
AVP-21D9 94
ETI-204 94
CHAPTER 6 ANTIFUNGALS 96
Resistance and toxicity have heightened the need for novel approaches to antifungal treatment 96
NeuTec/Novartis's Mycograb targets the highly conserved Hsp90 98
BIBLIOGRAPHY 100
Journal papers 100
Websites 111
Other 113
Contributing experts 115
APPENDIX B 116
About Datamonitor 116
About Datamonitor Healthcare 116
About the Disease analysis team 117
Disclaimer 118

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Table 1: Overview of anti-cell antibodies in development, 2008 50
Table 2: HCV pipeline overview 57
Table 3: Rabies pipeline overview 61
Table 4: West Nile virus pipeline overview, 2008 63
Table 5: SARS pipeline overview, 2008 64
Table 6: Staphylococcal pipeline overview, 2008 74
Table 7: Enterococcal pipeline overview 81
Table 8: Pipeline overview 85
Table 9: Pseudomonas pipeline overview 89
Table 10: Pipeline overview for B. anthracis infections 92


Figure 1: Summary of the main development issues 10
Figure 2: Summary of possible solutions to development issues 18
Figure 3: Antibody structure 21
Figure 4: Hybridoma technique for production of monoclonal antibodies 23
Figure 5: Murine, chimeric, humanized and human antibody structures 26
Figure 6: Percentage of products in Phase I-III development by type of infection 32
Figure 7: Respiratory syncytial viral structure 37
Figure 8: HIV fusion and entry 46
Figure 9: HIV antibody mechanism of action 47
Figure 10: HCV etiology 56
Figure 11: Total number of patients developing nosocomial infections in an average year in the US 66
Figure 12: S. aureus virulence factors 73

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