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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
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