I had a presentation Biopharma Orphan Drug Congress during Sep. 14-15 in Seoul.

1. Developing orphan
drugs in Asia:
Successful
collaborative effort
between biotechs &
policy makers
Fred Lin
Sep. 15, 2011

2. Orphan drugs become a
focus
• Replace the loss of revenues as their products
lose patent protection
• Reduced competition
• Effective drugs can be priced at a premium
• Smaller patient populations allow for smaller
trials which can be completed more rapidly at a
reduced cost
• Reduces the need for complex and expensive
physician marketing campaigns
• Increasing of medical care on rare disease
patient as economic growth of country

3. Legislation of Orphan Drug
Market Overview
Act
US Orphan Drug Act 1983
Singapore The medicine (Orphan Drug)
exemption Order 1991
Japan Orphan Drug Legislation 1993
Australia Orphan Drug Program 1998
EU Orphan Drug Legislation 2000
Taiwan Rare Disease and Orphan Drug
Act 2000

4. Rare disease & Orphan Drug
• Ideally:
– Rare Disease is Disease with Low Prevalence and
– Most rare diseases are results of genetic defects, and
are often described as congenital diseases
– Due to the high cost of developing medical treatment
and special nutrients and a small market with so few
patients, pharmaceutical industry is not willing to
develop, produce or import those products. Therefore,
those medical treatment and nutrients are called
“Orphan Drugs”
• Reality
– Different country has different definition due to country’s
specific situation
– Financial support of the medication is the big concern.

5. Definition of Rare Disease
Prevalence criteria Per 100,000
US < 200,000 patients / year 7.5/10,000
Canada < 200,000 patients / year 7.5/10,000
Japan < 50,000 patients / year 4.0/10,000
Australia < 2,000 patients / year 1.1/10,000
EU < 185,000 patients / year 5.0/10,000
Taiwan < 2,000 patients / year 1.0/10,000

6. Rare Disease and Orphan Drug Act
• Commenced since 2000
• Stakeholders:
– Patients
– TFRD (Taiwan Foundation of Rare Disorders)
– Bureau of Pharmaceutical Affairs (TFDA now)
– Orphan drug advisory committee
– Legislation Yuan and legislators
– Public media

7. Funding & Subsidization
• Government shall place the budget for
RARE Disease Treatment which is
separated from National Health Insurance
Budget.
• Government shall finance those
international medical cooperation project
of which approved by central medical
committee.
• All related diagnosis, medical treatment,
nutrients can be subsidized.

8. Pay for Rare Disease
National Health
Insurance Budget
Rare Disease
Budget

9. Usage of Orphan Drug
• The major indications of the medicinal
products are for the prevention, diagnosis,
and treatment of rare diseases.
• Medicinal products that have been
approved by other countries.
• Documents required for registration and
market approval, review procedures, and
other relevant issues shall be regulated by
the central competent authority
• Local clinical trial may require if necessary
• Permit license valid for ten years with
exclusivity

10. Definition of Rare Disease in
Taiwan
1. Rarity
2. Refractory to conventional
therapy
3. Genetic (mainly) and
Metabolic diseases

11. Process of Orphan Business
Name patient base
Importation Regular importation
Company Reference price, Importation price
Orphan Drug Reimbursement with expected profit
Reimbursement criteria
Patent production
Product Dossier availability
registration Others
Check if rare Listing of
disease listed orphan drug
Specialist Patient available
YES Medical Clinical support & Significance
institute Reference approval country
NO

12. Industrial Aspect
1. Definition of orphan drug is
different from US and EU
2. The treatment and subsidization
of the therapy are written in law
3. Patient service and source are
the key marketing focus
4. Growing market with moderate
but stable profit margin.

13. Market Size of Orphan
Drugs
Taiwan
Current related information:
No. of Rare disorders: 185 items announced
No. of orphan drugs: 74 items listed
No. of orphan drugs reimbursed: 55
products
Reimbursement market size
No. of Patient reimbursed: ~ 2,700
Reimbursed orphan drug: ~ USD 50-55
million

14. Some Examples
Indication Product
Alpha-galactosidase A deficiency (Fabry disease) Agalsidase-alpha (Replagal), Agalsidase-beta (Fabrizym)
Gaucher's disease type I 第一型高雪氏症 Imiglucerase (Cerezym), Miglustat (Zevasca)
Bosentan, Epoprostenol, Iloprost, Treprostinil sodium,
Primary pulmonary hypertension 原發性肺高血壓 Ambrisentan, Sildenafil citrate
Niemann-Pick Disease Miglustat (Zevasca)
Pompe disease 龐貝氏症 Alpha-glucosidase (Calzyme)
Multiple Sclerosis 多發性硬化症 Glatiramer acetate, Interferon-Beta-1a, Natalizumab
DiGeorge Syndrome Thymosin alfa 1
Huntington disease 亨汀頓氏舞蹈症 Tetrabenazine
Laron Syndrome Recombinant human insulin-like growth factor 1, rhIGF-1
Mucopolysaccharidosis VI 黏多醣症第6型 Galsulfase
Mucopolysaccharidosis I 黏多醣儲積症第一型 Laronidase
Nephropathic cystinosis Cysteamine Bitartrate
Wilson Disease威爾森氏病 Trientine HCl, Zinc Acetate
Hunter Syndrome Idursulfase (Elaprase)

15. Expenditure of Rare Disease
70
USD (M) 57.9
60
50.5
50 44.9
36.1 37.1
40
30 25.3
20
10
0
2005 2006 2007 2008 2009 2010

16. Attractiveness of Orphan Business
• Treatment on patient with rare disease is
protected by law
– government has obligation to guarantee availability
of the product supplier
– guarantee market growth
– global pricing
• Less administration hurdle
– regulatory process and lead time
– hospital listing
– reimbursement application
• Less competition
– first mover advantage: take all existing patient at
one time and control source of new patient
– Replacement is not easy to happen

17. Characteristics of Orphan Market
• Patient
– Small number of patient with insufficient medical
knowledge
– Suffering in seeking optimal medical support
– Family involved
• Physician
– No so many doctors familiar with the disease and the
treatment
– No so many doctors are interest on caring the disease
and the patient
• Finance and Incentive
– Treatment cost is high and never the ending
– Most patients can not afford to the treatment

18. Challenges
• Market size / Patient number
– Theoretical market size
• Prevalence rate
• Incidence rate
– Accessible market size
• Awareness of the disease
• Late, miss or neglected diagnosis
• National Screen Project
– Actual market size
• Affordability (Reimbursement, social support,
insurance, …)
• Diagnosis availability

19. Key successful factors
• Become the first mover
• Science leads to the business
• Patient is the focus
• Collaboration with professional society,
charity society and patient foundation
• Financial supporting program
• Professional & service oriented
representative
• Good connection with media and law
makers

20. Case 1: ZXX in NPC
• Doctor
• Patients
• Public media
• Local distributor
• Orphan drug under development
• Compassion use
– 50% free, 50% charged by supplier
– TFRD, Social charity funding and TNHB
• Rare disease committee and Taiwan DOH (TFDA
now)
• EMEA approval
• Taiwan approval immediately

21. Case 2: Multikine
• Orphan drug in US but not in Taiwan
• OEP joins in clinical development to
exchange distribution right in the
territories.
• Global phase III study makes product
approval at same time as US.
• May consider business of NPB before
license approval.

22. Summary
• Definition of Orphan drug in Western
countries do not exactly the same as
Asia countries
• Rare disease is not a matter of
medical care but social care.
• Name patient basis is mostly used
business model
• Dealing unexpected situation is a
NORM for doing orphan business

23. Q&A