Content
Executive Summary
Chapter 1: An Introduction to Orphan Drugs
Report purpose
Approach and methodology
Report outline
Chapter 2: Orphan Drug Activity Outside Europe
The impact of more than 20 years of US orphan drug legislation
Regulations and procedures
The US
The Orphan Drug Act
Orphan drug designation
Orphan drug incentives
Japan
Definition of an orphan product
The role of the OPSR
The role of the MHLW
Australia
Key incentives
Characteristics of the orphan drug programme
Singapore
Definition
Legal framework for imports
Impact and uptake
Orphan drug designations
Orphan drug approvals
Leading orphan drug companies
Leading orphan drugs
Chapter 3: Case Studies of Leading Orphan Drugs
Epogen (Amgen)
Anaemia associated with end-stage renal disease
Anaemia in Zidovudine-treated HIV-infected patients
Sales trends
IntronA (Schering-Plough)
AIDS-related Kaposi's sarcoma
Chronic hepatitis C in paediatric patients
Sales trends
Remicade (Johnson & Johnson)
Moderately to severely active Crohn's disease
Sales trends
Rituxan (Genentech)
Non-Hodgkin's B-cell lymphoma
Sales trends
Enbrel (Amgen)
Moderately to severe active juvenile rheumatoid arthritis
Sales trends
Neupogen (Amgen)
Neutropenia in cancer patients receiving bone marrow transplant
Severe chronic neutropenia
Peripheral blood progenitor cell collection and therapy
Acute myeloid leukaemia receiving induction or consolidation chemotherapy
Sales trends
Avonex (Biogen IDEC)
Multiple sclerosis
Sales trends
Gleevec/Glivec (Novartis)
Chronic myeloid leukaemia
Gastrointestinal stromal tumours
Sales trends
Topamax (Johnson & Johnson)
Lennox-Gastaut syndrome
Sales trends
Taxol (BMS)
AIDS-related Kaposi's sarcoma
Sales trends
Chapter 4: Orphan Drug Regulations in Europe
Summary
Current legislation and regulations
History of European orphan drug legislation
Key purposes of European orphan drug legislation
Defining an orphan drug
The Committee for Orphan Medicinal Products
The designation procedure
Key incentives
Protocol assistance
Community marketing authorisation
Market exclusivity
Other incentives
Subsequent regulations
Orphan drug designation applications
Orphan drug designation procedures
Orphan drug designation fee reductions
Orphan drug designation protocol assistance
Orphan drug designation inventory of incentives
Key protagonists
The Committee for Orphan Medicinal Products
The European Agency for the Evaluation of Medicinal Products
The European Commission/European Parliament
Patient groups
European Organisation for Rare Diseases (Eurordis)
European Alliance of Patient and Parent Organisations for Innovation in Genetic Services (EAGS)
Industry representatives
Learned societies
Key benefits and limitations
Key benefits
Key limitations
Cross-regional comparison
Key ambiguities
'Significant benefit'
'Similar product'
'Medical plausibility''
'Prevalence'
Trade name
Future legislation and regulations
Budget
Coverage
US model
Chapter 5: European Orphan Drug Activity
Orphan drug designations
Key orphan drug indications
Key orphan drug companies
Key orphan drug timelines
Key orphan drug strategies
Extended indications/formulations of non-orphan drugs
Global orphan drug designations
Size of target indication prevalence
Stage of development at designation
Special licences for pre-approval use
Chapter 6: Fabrazyme - Genzyme Europe
Overview
Clinical pharmacology
Fabry disease
Development trials
Pivotal clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 7: Replagal - Transkaryotic Therapies
Overview
Fabry disease
Incidence/prevalence of Fabry disease
Development trials
Pivotal clinical trial
Other clinical trials
Fabry Outcome Survey
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 8: Trisenox - Cell Therapeutics (UK)
Overview
Acute promyelocytic leukaemia (APL)
Myelodysplastic syndromes
Development trials
Pivotal clinical trials
Other clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 9: Zavesca - Actelion Registration
Overview
Gaucher disease description
Affected individuals
Prevalence and incidence of Gaucher disease
Development trials
Pivotal clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 10: Carbaglu - Orphan Europe
Overview
N-Acetylglutamate synthase (NAGS) deficiency
Development trials
Pivotal clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 11: Busilvex - Pierre Fabre Mdicament
Overview
Haematopoietic progenitor cell transplantation
Conditioning regimen
Rationale for intravenous high-dose busulfan
Development trials
Pivotal clinical trials
Other clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 12: Aldurazyme - Genzyme Europe
Overview
Mucopolysaccharidosis, type I
Signs and symptoms
Disease progression
Development trials
Pivotal clinical trials
Other clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 13: Glivec - Novartis Europharm
Overview
Indications and usage
Drivers
Barriers
Chronic myeloid leukaemia
Development trials
Pivotal clinical trials
Other clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 14: Somavert - Pharmacia Enterprises
Overview
Acromegaly description
Prevalence and incidence of acromegaly
Development trials
Pivotal clinical trials
Adverse events
Other clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 15: Tracleer - Actelion Registration
Overview
Pulmonary arterial hypertension description
Development trials
Pivotal clinical trials
Other clinical trials
Development and regulatory timelines
CPMP conclusions
CPMP Decision
Post-marketing programme
Steps taken after granting the marketing authorisation
Commercial impact
Chapter 16: Four Other Key Orphan Drugs
Ventavis
Litak
Onsenal
PhotoBarr
Chapter 17: Key Conclusions and Recommendations
Key orphan drug strategies
Elements in the design of an orphan drug strategy
Trial design and initial indication approved
Speed to market
Pricing
Profile raising
Licensing and marketing agreements
Key success stories and bottlenecks
Glivec: a success story
Somavert: an example of bottlenecks
Key recommendations
List of Figures
Figure 2.2 - US orphan drug approvals, 1983-2004
Figure 2.3 - Leading companies by US orphan drug designations, 1983-2004
Figure 3.1 - Epogen global sales, 1999-2003
Figure 3.2 - IntronA global sales, 1999-2003
Figure 3.3 - Remicade global sales, 1999-2003
Figure 3.4 - Rituxan global sales, 1999-2003
Figure 3.5 - Enbrel global sales, 1999-2003
Figure 3.6 - Neupogen global sales, 1999-2003
Figure 3.7 - Avonex global sales, 1999-2003
Figure 3.8 - Gleevec/Glivec global sales, 2001-03
Figure 3.9 - Topamax global sales, 1999-2003
Figure 3.10 - Taxol global sales, 1999-2003
Figure 4.1 - The orphan designation procedure
Figure 6.1 - Fabrazyme: key development and regulatory timelines
Figure 6.2 - Fabrazyme sales, 2001-04
Figure 7.1 - Replagal: key development and regulatory timelines
Figure 7.2 - Replagal sales, 2002-04
Figure 8.1 - Trisenox: key development and regulatory timelines
Figure 8.2 - Trisenox sales, 2002-04
Figure 9.1 - Zavesca: key development and regulatory timelines
Figure 9.2 - Zavesca sales, 2003/04
Figure 10.1 - Carbaglu: key development and regulatory timelines
Figure 11.1 - Busilvex: key development and regulatory timelines
Figure 12.1 - Aldurazyme: key development and regulatory timelines
Figure 12.2 - Aldurazyme sales, 2003/04
Figure 13.1 - Glivec: key development and regulatory timelines
Figure 13.2 - Glivec sales, 2001-04
Figure 14.1 - Somavert: key development and regulatory timelines
Figure 15.1 - Tracleer: key development and regulatory timelines
Figure 15.2 - Tracleer sales, 2001-04
Figure 17.1 - Components in a successful orphan drug strategy
Figure 17.2 - Key business strategies for orphan drugs
List of Tables
Table 2.1 - Leading orphan drugs, 2002/03
Table 3.1 - Epogen (erythropoietin alfa) - drug monograph
Table 3.2 - IntronA/Rebetol (interferon alfa-2b/ribavirin) - drug monograph
Table 3.3 - Remicade (infliximab) - drug monograph
Table 3.4 - Rituxan (rituximab) - drug monograph
Table 3.5 - Enbrel (etanercept) - drug monograph
Table 3.6 - Neupogen (filgrastim) - drug monograph
Table 3.7 - Avonex (interferon beta-1a) - drug monograph
Table 3.8 - Gleevec/Glivec (imatinib mesilate) - drug monograph
Table 3.9 - Topamax (topiramate) - drug monograph
Table 3.10 - Taxol (paclitaxel) - drug monograph
Table 4.1 - Cross-regional comparison of orphan drug programmes
Table 5.1 - Orphan drug activity, 2000-04
Table 5.2 - Key orphan drug indications
Table 5.3 - Orphan drugs with multiple indications
Table 5.4 - Key orphan drug companies
Table 5.5 - Orphan drugs with multiple sponsors
Table 5.6 - Orphan drugs receiving market authorisation
Table 5.7 - Global orphan drugs
Table 6.1 - Fabrazyme (agalsidase beta) - drug monograph
Table 7.1 - Replagal (agalsidase alfa) - drug monograph
Table 7.2 - Overview of clinical trials programme
Table 8.1 - Trisenox (arsenic trioxide) - drug monograph
Table 9.1 - Zavesca (miglustat) - drug monograph
Table 10.1 - Carbaglu (carglumic acid) - drug monograph
Table 11.1 - Busilvex (busulfan) - drug monograph
Table 12.1 - - Aldurazyme (laronidase) - drug monograph
Table 13.1 - Glivec (imatinib mesilate) - drug monograph
Table 13.2 - EMEA (EU) approved indications for Glivec
Table 14.2 - Somavert (pegvisomant) - drug monograph
Table 15.1 - Tracleer (bosentan) - drug monograph
Table 17.1 - Marketing submission to approval for orphan drugs in Europe
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