Mihaela Ianosev – European Medical Director CDBU

Industry Expectations:

Discovery, Research, Development ,

Access to medicines

Pharmaceutical R&D Ecosystem – radical changes

￭ Change in demographics

￭ R&D productivity

￭ Rapid escalation of the costs of R&D

￭ Higher risks of failure associated with greater innovation

￭ Global tightening and conservatism of regulatory policy

￭ Diminishing advantages of being first to market

￭ Changes in social expectations

￭ Patent expiration

￭ Science & Technology

￭ Economical crisis

￭ HTA, pricing & reimbursement

1. Priorities for Research

2. Value based development and access

to medicines

3. Modalities of Discovery

Un

sa

tisfie

dN

ee

d

Priorities of Research

important

moderate

modest

Added Benefit

Level of Innovation

Diseases with mostly

satisfied needsUn

sa

tisfie

dN

ee

d

Added Benefit

Priorities of Research

Orphan Diseases

Diseases with residual needs

Diseases with off

patent drugs

Priorities of Research

Rate of Orphan Product Approvals Remain Flat

All Orphan Designations

and Approvals (USA)

0

20

40

60

80

100

120

140

y 2001

y 2002

y 2003

y 2004

y 2005

y 2006

y 2007

y 2008

y 2009

y 2010

All Orphan Designations

and Approvals (EU)

0

50

100

150

200

250

y 2000y 2001y 2002 y 2003y 2004y 2005y 2006y 2007y 2008y 2009y 2010

Orphan Designations

Approvals

Orphan Designations

Approvals

Rare Diseases Drug Development

a Challenging Reality

Substantial heterogeneity of patient population

Difficulty in clearly defining the patient population – clinical

presentation, disease subtype

Small patient populations

Difficulty in demonstrating statistical significance

Geographically dispersed patients – recruitment

Limited clinical experiences

Common problems for medical sites, industry and agency

Challenge of defining practical clinical endpoints

Traditional study designs often not feasible

Randomization of trials and inclusion of control arms can be untenable

Double-blind design with placebo or standard of care is often difficult

to apply

Regulatory expectations established primarily for more common

diseases => big, long clinical studies

8

Access to Rare Diseases Treatments

Opportunities for Policy Optimisation

10 solutions to accelerate access to treatments in rare diseases

Nature Reviews

Drug Discovery

1. Importance of continued flexible orphan incentives

2. Role of Patients’ disease registries & post-approval studies

3. Global Simplification-Harmonization of regulatory requirements

9

Patient Timely Access to Rare Diseases Treatments

Development Process as a Continuum

1. Accelerated and Conditional

approval should become the

default pathway in this priority

population provided sufficient

dialogue has taken place

between patients, physicians,

drug developers and HTA.

2. Progressive assessment

and approval mechanism

as a standard practice

April 2012

Compelling arguments:

- small patient population

-Concentration of clinical

research activities in CoE

- High level of specialization of

the treating physician

- Wealth of scientific knowledge

among patients & their families

= high quality interaction with

the clinician

10

Value & Specificity of the Rare Diseases

Model the Policy Equation

Industrial policy

Health policy

Unmet need

Patient care & access

Equity & solidarity

R&D innovation

Economic ROI

Industry competitiveness

Health Budgets

11

4. Moderate

improvement

1. Small

improvement

7. Major

improvement

Rare Disease Unmet NeedMedicine Therapeutic

Benefit

Medicine Therapeutic

Value

Treatment

available

Treatment

Social

outcome

Disease

Clinical

severity

Treatment

Clinical

Benefit

and outcome

Disease

Social Impact

Value attributes

Value criteria definition

Treatment

innovation

Define Medicine Therapeutic Value

0

20

40

60

80

100

120

Germany Taiwan Malaysia Brazil China

Monthly Price Index

Illustrative case studyGlobal patient reach

Patient Access & Global Reach

Tiered pricing based on payers’ willingness/ability to pay

Germany

Taiwan

Malaysia

BrazilChina

Tier 4 Tier 5Tier 3Tier 2Tier 1

1

2High income

3Upper Middle Income

4Middle Income

5

Low Middle Income

USA +EU + Japan

Modalities of Discovery

Coopetion & Collaboration

1. Among Companies

Pre-competitive research

2. Knowledge Chain

Universities, Charities, Foundations, No profit

Start Up, Micropharma

Coopetion & Collaboration

TransCelerate BioPharma Inc.

Scope: identify and solve common drug development challenges with

the end goals of improving the quality of clinical studies and

bringing new medicines to patients faster

Initial area of focus = clinical study execution

1. development of a shared user interface for investigator site

portals

2. Mutual recognition of study site qualification and training

3. Development of risk-based site monitoring approach and

standards

4. Development of clinical data standards

5. Establishment of a comparator drug supply model

As shared solutions will be developed – will involve industry alliances

(ex. Clinical Data Interchange Consortium, Critical Path Institute,

Clinical trials Transformation Initiative), regulatory bodies (FDA,

EMA) and CROs.

Coopetion & Collaboration

1. Among Companies

Pre-competitive research

2. Knowledge Chain

Academia, Charities, Foundations

Start Up, Micropharma

Modalities of Discovery – The “How”

Preliminary Experience

20

GSK Rare Diseases

Small molecule pharmacological

chaperones

Oligonucleotides

Gene therapy

Enzyme replacement therapy

Rare Diseases Investment Dynamics

Alliances & Partnerships

Our mission

To improve the quality of human life

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live longer

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