Developing orphan Developing orphan drugs in Asia: drugs in Asia:

Successful Successful collaborative effort collaborative effort between between biotechsbiotechs & &

policy makerspolicy makersFred LinFred Lin

Sep. 15, 2011Sep. 15, 2011

Orphan drugs become a Orphan drugs become a focusfocus

• 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

Legislation of Orphan Drug Legislation of Orphan Drug ActAct

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

Market Overview

Rare disease & Orphan DrugRare 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.

Definition of Rare DiseaseDefinition 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

Rare Disease and Orphan Drug ActRare 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

Funding & SubsidizationFunding & 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.

Pay for Rare Disease Pay for Rare Disease

National Health Insurance Budget

Rare DiseaseBudget

Usage of Orphan DrugUsage 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

Definition of Rare Disease in Definition of Rare Disease in TaiwanTaiwan

1. Rarity2. Refractory to conventional

therapy3. Genetic (mainly) and

Metabolic diseases

Process of Orphan BusinessProcess of Orphan Business

CompanyOrphan Drug

SpecialistMedical institute

Check if rare disease listed

Patient availableClinical support & SignificanceReference approval country

NO

YES

Listing of orphan drug

Reimbursement

Product registration

ImportationName patient baseRegular importation

Reference price, Importation price with expected profitReimbursement criteria

Patent productionDossier availabilityOthers

Industrial AspectIndustrial Aspect1. Definition of orphan drug is

different from US and EU2. The treatment and subsidization

of the therapy are written in law3. Patient service and source are

the key marketing focus4. Growing market with moderate

but stable profit margin.

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 sizeNo. of Patient reimbursed: ~ 2,700Reimbursed orphan drug: ~ USD 50-55 million

Some ExamplesSome ExamplesIndication 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)

Primary pulmonary hypertension 原發性肺高血壓

Bosentan, Epoprostenol, Iloprost, Treprostinil

sodium, 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)

Expenditure of Rare DiseaseExpenditure of Rare Disease

25.3

36.1 37.1

44.950.5

57.9

0

10

20

30

40

50

60

70

2005 2006 2007 2008 2009 2010

USD (M)

Attractiveness of Orphan BusinessAttractiveness 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

Characteristics of Orphan MarketCharacteristics 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

ChallengesChallenges• 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

Key successful factorsKey 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

Case 1: ZXX in NPCCase 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

Case 2: Case 2: MultikineMultikine• 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.

SummarySummary• 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

Q&AQ&A