Patients association and orphan drug development

The example of AFMTELETHON

Serge Braun, PharmD, PhD

CSO, AFMTELETHON

> 7000 diseases (80% inherited)

3-4% births

Europe: 30 Million

Rare diseases, a neglected public health issue :

Rare disease patients = 3 X cancer patients = 4 X Alzheimer Worldwide research effort 10 x lower

Unbalanced prevalence and research efforts :

> 50-100M / drug ?

Development costs growing exponentially :

The context

Since 1987

30 hrs of TV marathon

10 000 towns and cities

53 000 associations

200 000 volunteers

5 millions participants

1 million donors

R&D 51%

(60,6M)

Social missions

31%

Rund raising

11%

Running costs 7%

Budget 2012 : 119,7 M

http://www.toutafm.org/e_img/chapitres/telethon02.jpghttp://www.toutafm.org/e_img/chapitres/telethon03.jpg

Extension to other rare diseases and to frequent diseases

Preclinical / clinical development

Proof of concept on rare diseases

Identify therapeutic strategies

Understand the diseases Regroup patients Identify genes Pathophysiology

Gene-based therapies Cell therapies Pharmacology

Toxicology Optimization Formulation Manufacturing, scale-up Clinical trial design and management

AFM Strategy

Extension to other rare diseases and to frequent diseases

Preclinical / clinical development

Proof of concept on rare diseases

Identify therapeutic strategies

Understand the diseases Regroup patients Identify genes Pathophysiology

Gene-based therapies Cell therapies Pharmacology

Toxicology Optimization Formulation Manufacturing, scale-up Clinical trial design and management

AFM Strategy

Funded Applications by Field AFM 2012 R&D Budget = 60M

Data reported in the AFM 2012 Annual Report (http://www.afm-telethon.fr)

AFMTELETHON

- serve as disease-specific experts

- reduce bottlenecks/barriers for entry into

rare disease area

- a source of innovation for frequent disorders

access to knowledge, expertise , and patients for all levels of the process

of product development

tools, training and experts that would be difficult or time-consuming for

pharma/biotech companies to develop (e.g. in vitro / in vivo assays, outcome measures, biomarkers, clinical study data, DSMB, patient registries, biobanks, disease

natural history data, CIC networks)

resources (e.g. GMP manufacturing, patient enrolment, training, informed consent forms)

cost / risk sharing

A voice: lobbying and reimbursement, ethics and regulatory committees,

EU commissions,

Provides :

BONE MARROW DISORDERS:

White blood cells: - immunodeficiencies (GSK/Telethon Italia)

- adrenoleukodystrophy

Red blood cells : - -thalassemia/ Sickle cell

disease (BlueBird Bio)

The resurrection

of gene therapy

Long term commitment

Heavy fundings

Networking, lobbying

Caen

Strasbourg

Rouen

Lille

Rennes

Brest

Roscoff

Limoges

Besanon

Reims

Montpellier

Lyon

St Etienne Grenoble

Nantes

Angers

Nice

Marseille

Ile de France

Amiens

Hendaye

Bordeaux

Pau

Agen

Tours

Toulouse

Guyane

Guadeloupe

Martinique

La Runion

Nouvelle

Caldonie

Cayenne

Pointe Pitre

Fort de France

St Pierre

St Denis

Nouma

Clermont

Ferrand

Palavas

Dijon

ILE DE FRANCE

Paris

Garches Necker

St-Vincent de

Paul

AIM

Trousseau

Kremlin

Bictre

Crteil

Nancy

Consultations

CHildren Consultations

Adules

Consultations

Adults/Children

Poitiers

Labellis

Labellis

Labellis

Labellis

Labellis

Labellis

Labellis

Labellis

Mulhouse

V. dAscq

Labellis

Reference clinical centers

60%

France and abroad

40%

220 scientists

Gene therapy of

rare diseases

(from bench to

bed)

270 MDs, PhDs, and

techs,

50 % AFM, 50 % Hospital

/ INSERM / UPMC

85 scientists

50 % AFM

50 %

INSERM

Stem cells

An integrated environment for

biotherapies for rare diseases

Atlantic Gene

Therapies

Nantes

213 R&D projects

19 scientific meetings

77 Fellowhsips

11 projects in parntership with other

patient

> 20 Large programs

> 30 clinical trials

http://img381.imageshack.us/img381/1291/previewtl7.jpg

Along the line of a strategy of general interest:

Genethon Bioprod

Investment Budget : 28,5 M

(AFM : 5,5 M + land owner)

A Priority because:

Clinical-grade production is a bottleneck for clinical trials,

No production center in the world that can meet the needs

5.000 m, 4 production Suites for cGMP production (AAV, LV),

BL3 confinement and High Environmental Quality (QEH).

The largest ww GMP production plant for gene-therapy products, to support clinical trials

Develop Methods testing

Non clinical

studies

Clinical

phase

Tox batch

Preclinical

phase

GMP batch

DNA RNA Protein Immunology - Viral Safety

Develop Methods testing

QC testing of

viral vector batches

Follow-up of

research subjects

Develop Methods

Tests

Facilities: 650 m2. 6

BSL1, 6 BSL2, 1 BSL3.

Launched in 2004

GLP compliance since

2008

www.plateforme-maladiesrares.org

Rare Diseases National Plan

PATIENT

ORGANISATIONS INDUSTRY

Biotechs (i.e. Trophos,

Prosensa, Santhera,

Cellectis, Rhenovia,)

Big Pharmas (Roche)

Spin-off companies

Multiple partnerships

International dimension

DRCI (MDA, PPMD, UPPMD)

Eurordis

Alliance Maladies Rares

MD Canada

SMA Europe

Telethon Italia

Retina France

IRME

VLM

Alliance SanFilippo

ENMC

NETWORKS TREAT-NMD

IRDIRC

Myores, MyoAge, MyoAMP

NMD-Chip,

INSTITUTIONS

INSERM

AP-HP

CNRS

CEA

Institut Pasteur

Universities

IGBMC

Fondation Imagine

Fondation Maladies

Rares

In return for their support and risk-taking patient groups claim rights

on industrial property, and share of profits (back to research).

An emerging business model for patient groups with open questions:

What partnerships with the pharmaceutical industry ?

What partnerships with end-payers ? (ROI)

What pricing strategies for projects supported by patient groups ?

A new business model for patient groups?

Spin-offs

- Genosafe

- Lysogene

Fondations / Non-for-profut companies

- Esperare

- Halo Therapeutics now DART Therapeutics

- RarePartners

Rare diseases funds

- Cydan: $16M (Motts NEA, Pfizers corporate venture fund et

Alexandria Real Estate Equities Inc

- Kurma Biofund II: 44M dont GSK (17.5 M)

- Sanofi-Genzyme: $100M

and other big Pharma funds

- New Enterprise Associate (NEA): $16M

- CureDuchenne Ventures

Europe

- 144M (38 within IRDIRC)

AFM/CDC fund

fair, mastered

price

http://www.netcarshow.com/bugatti/2009-veyron_centenaire/800x600/wallpaper_02.htm

40$ to 2M$

Shey et al.

Orphanet Journal of Rare Diseases (2011)

Annual cost /patient (Europe) : 1251 to 407 631

mean : 32 242.

Nephropathic cystinosis

2000 patients worldwide

Drug: cysteamine bitartrate

Cystagon (Orphan Europe) : $10K / y

Procysbi (Raptor): slow release oral form

Phase III (43 patients)

Analysts: $200-$300K

Scenarios : (88% penetration USA et 50% monde)

CA: 100K $119M / y

200K $238M

50K $59.5M

Fair price ?

3,4 DAP : UK 800 ($1,280) - 2,000 ($3,200)

Firdapse; > 40,000 ($64,000)

Licensed to Catalyst Pharmaceutical

Breakthrough Therapy Designation (27 aot 2013)

Annual sales BioMarin in Europe :

2010: 6.4 M$

2011: 13.1 M$

2012: 10.8 M$

(50M$ in 2017)

100 M$ North America for LEMS

FIRDAPSE

BENEFIT / RISK ratio

BENEFIT / PRICE ratio ?

Clinicians

End payers

Industry

Researchers PATIENT