Stakeholder Opinions Alpha 1 Antitrypsin Deficiency

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the disease market 4
Related reports 4
CHAPTER 2 DISEASE BACKGROUND 6
Alpha-1 antitrypsin deficiency is a hereditary disease found mainly in Caucasians 6
Etiology of alpha-1 antitrypsin deficiency 6
Genetics of Alpha-1 antitrypsin deficiency 8
Epidemiology 10
Emphysema 12
Liver disease 14
Unmet needs 17
Risk factors 17
Smoking 18
Environmental tobacco smoke exposure 19
Occupational exposure 19
Bacterial infections 20
Body mass index 20
CHAPTER 3 DIAGNOSIS 21
Diagnosis of alpha-1 antitrypsin deficiency 21
Lung function 21
Imaging 21
Serum alpha-1 antitrypsin levels 22
Biochemical markers 22
Phenotyping 22
Diagnostic guidelines 22
Genetic screening 23
Increase in age at diagnosis and delay in diagnosis of alpha-1 antitrypsin deficiency 25
Problems with physician knowledge 27
Difficulty in conducting clinical trials in COPD 27
Declining smoking rates 28
CHAPTER 4 TREATMENT OPTIONS 29
Standard COPD therapy 29
Augmentation therapy 29
Therapeutic rationale 29
Market analysis 32
Cost and reimbursement 33
Antibiotic therapy 34
Organ transplant 34
Pulmonary rehabilitation, supplementary oxygen and genetic counseling 35
CHAPTER 5 FUTURE TRENDS 36
Inhaled alpha-1 antitrypsin augmentation therapy 36
Arriva/Hyland 37
Kamada 37
Talecris 37
Recombinant alpha-1 antitrypsin augmentation therapy 37
Gamma retinoid agonists 38
Gene therapy is in the far future 38
Alpha-1 antitrypsin replacement therapy in cystic fibrosis 38
Clinical trial endpoints 39
Continuing medical education 39
The role of patient support groups 40
Neonatal genetic screening 42
Transfer of treatments to the general emphysema population 43
CHAPTER 6 BIBLIOGRAPHY 44
Articles 44
Websites 49
List of Tables
Table 1: Alpha-1 antitrypsin levels in common genotypes 9
Table 2: Estimated prevalence of the five main phenotypes of alpha-1 antitrypsin deficiency in selected countries 11
Table 3: Estimated numbers of each of the five main phenotypes of alpha-1 antitrypsin deficiency in selected countries 12
Table 4: Classification of recommendations for genetic testing 24
Table 5: Comparison of augmentation therapies in the US 30
List of Figures
Figure 1: Alpha-1 antitrypsin production and activity 8
Figure 2: An example of three-generation pedigree with alpha-1 antitrypsin deficiency 10
Figure 3: Estimated numbers of PiZZ individuals in selected European countries 13
Figure 4: Liver disease in PiZZ patients by age 15
Figure 5: Association between liver dysfunction and age in PiZZ infants 16
Figure 6: Flow diagram of anticipated liver disease outcomes in PiZZ infants 17
Figure 7: Decline in lung function by smoking status 19
Figure 8: Hospital admissions for alpha-1 antitrypsin deficient patients in Norway, 2005 26
Figure 9: SWOT analysis of human, plasma derived augmentation therapy 33