Malalties Minoritàries i Medicaments Orfes

en l'Unió Europea: Reptes i Oportunitats per

la recerca biomèdica

Cicle de Seminaris sobre Malalties Rares

15 d’Octubre de 2014

Josep Torrent-FarnellCommitte Orphan Medicinal Products (COMP/EMA) London

IRDiRC Therapies Scientific Committe

Universitat Autònoma de Barcelona

Research and Innovation

Rare diseases: a challenge too big to be mastered alone

• Huge unmet medical needs for patients across the globe

• Small patient populations

• Scarce and scattered research resources and expertise

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Research and Innovation

Acquiring knowledge about genes and Rare Disease Phenotypes

Source: Kym Boycott 2014

4

What is an orphan drug?

• Drugs aimed to treat diseases which a

prevalence figure lower than 5 cases per 10,000

habitants.

• These includes vaccines, curative treatments,

preventives therapies and diagnostic agents.

• Does not include dietetic measures neither

medical devices.

European Regulation EC No 141/2000

5

Unmet medical needs for rare diseases require worldwide

joint efforts and policies to develop new orphan therapies

6

Orphan regulatory overview

• Sharing same objectives

• Similar incentives and criteria

BUT

• Different prevalence limits

• “Significant Benefit” criterion mandatory only for EU applications

1983 2000

7

Why Rare Diseases and Orphan Drug Development can be an opportunity for researchers?

• Rare diseases present a lot of unmet medical needs that should be faced up

and embrace more than 7000 multisystemic rare conditions.

• Orphan drug development (from bench-to-bed): opportunity for

translational biomedical research

• There is a regulatory framework that foster and help the research in orphan

drug development and it is coupled with a funding strategy by IRDiRC.

• Orphan drug designation by COMP (EMA) attracts innovation and could be

a tool for researchers institutions to push their research line projects and to

bring new therapies for the sake of patients and social benefit.

8

Orhan designation as a regulatory pathway

• COMP

• Investigational

• Incentives

• Medical condition

CHMP

EU Licensing

Benefit/Risc, Post-Marketing

Conditional Aproval

Therapeutic indication

“OUTCOME”

COMP

Review

(P, SB)

DESIGNATIONMARKETING

AUTHORISATION

“GATE OPENER”“MARKET ACCESS”

9

Main features of orphan designation

• Aimed to human medicines.

• Free procedure.

• Can be applied in any stage of drug development.

• Applicant can be an enterprise, academic institution or individual

• Settled on European Community (EU, Ice, Liech, Nor)

• European Commission Decision gives right to receive incentives

• Evaluation to obtain OD designation follows a non-stop clock 90 days procedure

10

European Criteria for Orphan Designation

• Rarity (lower than 5 cases per 10,000)

• Severity (chronically debilitating or life-threatening)

• Absence of alternative treatment / Significant Benefit

• Medical plausibility (scientific rationale)

• Overall orphan drug Development

11

Incentives

• Economic / Marketing conditions

• Reduction / waiving fees

• Marketing exclusivity in the UE for 10+2 yrs

• Drug development

• Protocol assistance

• National incentives (Member States)

• Priority in EU research programs (DG Research: Horizon 2020)

• Fostering Rare Disease care and policies to facilitate access to

new diagnosis and therapies (DG Sanco: EUCERD)

12

The European Medicines Agency

www.ema.europa.eu

The Committee for Orphan Medicinal Products

(COMP) is responsible for:

• Assessment of orphan drug applications

• Participation on Protocol Assistance

• Assessment on the maintenance orphan

criteria at the time of marketing

authorization

• Collaboration with other EU institutions and

FDA on regular basis

13

CHMP (Committee for Human Medicinal Products)

CVMP(Committee for Veternary Medicinal Products)

HMPC(Committee for Herbal Medicinal Products)

COMP(Committee for Orphan Medicinal Products)

CAT (Committee for Advanced Therapy Medicinal Products)

PDCO (Paediatric Committee)

PRAC(PhVig Risk Assessment Committee )

EMA Scientific Committees

14

COMP

Composition:

• Chair and Vice Chair

• 1 member/MS

• 3 patient reps

• 3 EMA reps

Experts and patients

invited

COMP meets regularly

3 days monthly

15

COMP/EMA: Orphan drug designationachievements

16

OD by therapeutic field

13%

13%

4%

8%30%

18%

14%

musculoskeletal&nervous systemMetabolism

Anti-infectious

Cardiovascular &respiratoryOncology

Haematology

Other

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Orphan designations

• By prevalence:

• More 3 cases per 10.000: 12%

• Between 3 and 1 cases per 10.000: 52%

• Less than 1 cases per 10.000: 36%

• By age:

• Adult only: 42%

• Adult and pediatric: 50%

• Pediatric only: 8%

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Orphan Drug Designations: Spanish sponsorships (fromApril 2000 to September 2014)

Advanced Medical Projects - Spain 1

Advancell - Advanced In Vitro Cell Technologies S.A. - Spain 2

Almirall S.A. - Spain 1

Bioncotech Therapeutics, S.L. - Spain 1

Bionure Farma SL - Spain 1

Centro de Investigación Biomédica en Red (CIBER) - Spain 2

Consejo Superior de Investigaciones Cientificas (CSIC) - Spain 1

Digna Biotech S.L. - Spain 4

Diomune S.L. - Spain 1

GP-Pharm S.A. - Spain 1

Laboratorios del Dr. Esteve, S.A. - Spain 2

Lipopharma Therapeutics SL - Spain 1

Minoryx Therapeutics S.L. - Spain 1

Natac Pharma S.L. - Spain 1

NOSCIRA, S.A. - Spain 1

Oryzon Genomics SA - Spain 1

Pharma Mar SA Sociedad Unipersonal - Spain 8

Prodimed S.A. - Spain 1

ProRetina Therapeutics S.L. - Spain 1

ProRetina Therapeutics S.L.

- Spain 1

Sanifit Laboratoris, S.L. - Spain 1

TiGenix S.A.U. - Spain 3

Valentia BioPharma S.L - Spain 1

Vall d'Hebron Institute of Research - Spain 1

VCN Biosciences S.L. - Spain 1

Total general 40

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Orphan Drug Designations: Spanish sponsorships (fromApril 2000 to September 2014)

Sponsor Active Substance Proposed Indication

Vall d'Hebron Institute of

Research - Spain

Vector based on an adeno-

associated virus serotype 2

backbone, pseudo-serotyped with

a type 8 capsid, which carries the

coding sequence of the human

TYMP gene under the control of

the human thyroxine binding

globulin promoter (Common)

Treatment of mitochondrial

neurogastrointestinal

encephalomyopathy

On 22 August 2014, orphan designation (EU/3/14/1326) was granted by the

European Commission to Vall d’Hebron Institute of Research, Spain.

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Orphan medicines authorized in EU

21

Orphan medicines authorized in EU

22

COMP/EMA: Orphan drug designationachievements

¿?

Research and Innovation

• 92 orphan medicines authorised by the EC covering 98 therapeutic conditions

• 1300 medicines under research and development designated as orphan medicines

• 1232+ designations given by the EC covering ~ 521 conditions

Main gap: differences between ODD for investigational and OD approved

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Contenido de la presentación

1. Marco regulatorio europeo de medicamentos huérfanos

2. Incentivos, criterios de designación y procedimientos

reguladores

3. Estrategias de futuro

PROGRESSIVE EVIDENCE

25

Hurdles on

development

orphan

medicines

Development

conventional

medicines

26

First action: Increase Scientific Advice / Protocol Assistance

• A tool that bring together all stakeholders involved to give the best

recommendations to sponsors in optimizing drug development to meet

the standards required for marketing authorization

• A meeting point to merge views from:

• Industry / Sponsor

• Academics / experts

• Patient associations

• Regulatory decision-makers: COMP/CHMP/CAT/PDCO

• HTA participation

• Possible (if wished): joint SA for USA (FDA) and EU (EMA)

• Aimed to solve the gap between designation and authorization

Great importance to apply

27

Impact of SA/PA in marketing authorisationopinions

56.82%

75.00%

43.18%

25.00%

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

Without SA With SA

Positive opinion

Negative opinion

28

Impact of adherence to SA/PA in marketingauthorisation opinions

60%

50% 50% 50%53%

86%

100%

77%

100%

90%

0%

20%

40%

60%

80%

100%

120%

Primary

endpoint

Choice of

comp.

Durat ion Stat ist ics total

negative opinion

Posit ive opinion

29

Second action: The way forward, improving the translational pathway

• Biomarkers

• Animal models

• Delivery mechanisms

• Proof of principle

Gene identification

Pathophysiology

• Diagnostic

• Natural history

• Patient registries

• Trial sites

• Outcome measures

Clinical investigation /

Trials • Regulatory requirements

• Ethics

• HTA/ Health Economics

• Pricing / Follow-up

• Access policies

Therapy delivery

Research and Innovation

www.irdirc.org

200 therapies and

means to diagnose most rare disease by

2020

A joint initiative between DG Research (EU) and National Institute Health (USA) started on 2009

eurordis.org

Therapies SC Recommendations

31

Guide policies and funding strategies

to reach the goal of 200 new therapies

by 2020 based on IRDiRC Policies and

Guidelines adopted in April 2013.

Sources: TSC members and its 4 WGs:

Orphan Drug-Development and Regulatory Processes

Biomarkers for Disease Progression and Therapy Response

Chemically-derived products including Repurposing

Biotechnology-derived products including Cell & Gene

Therapies

ECRD 2014, Berlin

eurordis.org

Strategy for

TSC Recommendations

32

Prioritise collaborative clinical development of

designated orphan products & other rare disease

therapies that have received scientific guidance from

regulatory agencies, with emphasis on highest unmet

patient needs with the potential to be approved by 2020.

To ensure the pipeline beyond 2020, prioritise also

products at the non-clinical stage with strong proof-of-

concept to support plausibility and with a commitment to

apply for orphan designation and to seek scientific

guidance from regulatory agencies

ECRD 2014, Berlin

eurordis.org

TSC Recommendations

for Funding Priorities

33

IRDiRC funders should consider funding of rare disease

clinical trials through two possible mechanisms:

International collaborative rare disease research and orphan

medicine development (“that takes best advantage of unique

expertise and availability of special resources”), irrespective of

geography or nationality of the applicants

International alignment of themes and coordination of the

process for calls for proposals

ECRD 2014, Berlin

Research and Innovation

HORIZON 2020

• The EU’s 2014-20 programmefor research & innovation (around € 80 billion)

• A core part of Europe 2020, Innovation Union & European Research Area

• Three priorities: Excellent science, Industrial leadership, Societal challenges

35

The last reflexion

• Fostering overall orphan drug development should contribute to

increase the working knowledge of rare diseases and bring new

therapies to those patients affected living with a rare disease…

• So… the access policies intended to ensure that professionals can

prescribe the use of authorized orphan medicines in appropriate

expert centers are becoming crucial to improve quality of life of rare

disease patients.

Who do that?

Designation and authorization of orphanmedicines. EMAActive participation of AEMPS

Health Ministry: Price and reimbursement conditions AEMPS: Compassionate use and clinical trials authorization

Integral health planning for RD and funding of healthand pharmacological interventions

DEPARTAMENT DE SALUT

SERVEI CATALÀ DE SALUT

Consell Assessor Malalties

Minoritàries

CAMM, 2009

C.A. Tractaments

Farmacològics d’Alta

Complexitat

CATFAC, 2010

Evidència

Impacte pressupostari

39

• Equity in medicines acces for treatment of rare diseases

• Medium and long-term sostenibility of catalan health system

• Improve health outcomes

• Do not hamper therapeutic innovation

Catalan policies regarding orphan drugs

Budgetary impact of authorized OD and number of patients treated in the catalan health system

Budgetary impact by ATC classification groups (2011)

15%3%

12%

3%

2%

61%

1% 3%

Percentatge de la despesa total en funció de la categoria ATC (Any 2011)

A.- Sistema digestiu imetabolisme

B.- Sang i òrganshematopoètics

C.- Sistema cardiovascular

G.- Sistema genitourinari ihormones sexuals

H.- Preparacions sistèmiqueshormonals, excloent hormones

sexuals i insulinesL.- Antineoplàsics i agentsimmunomoduladors

Rare diseases and orphan

drug development are a

great opportunity for

researchers and clinicians

to further contribute to

increase knowledge

generation in rare diseases

by enhancing translational

research.

Be ready for it!