1. Advanced Therapy Medicinal Products - ATMPs -
A case study in health economics: ChondroCelect
ATMP - D.Dubois
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2. A representative sample of the slides that will be presented and discussed during the course is displayed hereafter.

3. ATMP’s ATMPs include: Centralised procedure registration
Gene therapy medicinal products
Somatic cell therapy medicinal products
Tissue-engineered products
Centralised procedure registration
Principles of existing legislation on medicines apply:
Marketing authorisation
Demonstration of Quality, Safety and Efficacy
Post-authorisation vigilance
ATMP - D.Dubois
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4. Unique features in the ATMP regulation
Risk-based approach to determine level of data
Post-authorisation follow-up of safety and efficacy
Incentives and fee reductions
ATMP - D.Dubois
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5. ChondroCelect First cell-based medicinal product
authorized under the European ATMP framework
(Regulation 1394/2007)
ATMP - D.Dubois
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6. Controlled manufacturing
ChondroCelect as medicinal product:
Autologous cell-based medicinal product (EU/1/09/563/001)
Characterised autologous cartilage cells expanded ex vivo expressing specific marker proteins
Repair of single symptomatic cartilage defects of the femoral condyle of the knee (ICRS grade III or IV) in adults.
Product
Active substance
Indication
Biopsy
Implantation
Controlled manufacturing
Quality control
ATMP - D.Dubois
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7. ChondroCelect – ATMP development
Underlying research (ECFA-Assay and ChondroCelect molecular markers)
Pre clinical testing & validation
Phase III Clinical trial
Compassionate use in 370 patients
Marketing authorization application at EMA*
EC Approval
Post MA Follow-up
2001
2002
2003
2004
2005
2006
2007
2008
2009
Year
Outcome of 15 years of R&D > 500 patients treated till date
ATMP - D.Dubois
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*EMA : European Medicines Agency

8. CC clinical evidence: superior structural repair at 12 months
Microfracture
ChondroCelect
The American Journal of Sports Medicine , Volume 36, No 2, February 2008
ATMP - D.Dubois
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9. CC clinical evidence: superior clinical benefit over MF over 36 months
Longitudinal analysis:
treatment effect at 36m
(mixed linear model)
KOOS
P-value
Overall(1)
0.048
Pain
0.044
Symptoms
0.123
Activity (ADL)
0.064
Sports
Quality of Life
0.036
ATMP - D.Dubois
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The American Journal of Sports Medicine , Volume 37 – Suppl. 1, November 2009

10. ATMP - D.Dubois
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11. Model structure – from model entry to OA onset after 15 years
During the 3 years following the knee intervention (microfracture [MFX] or autologous
chondrocytes implantation [ACI] using ChondroCelect [CC]), the symptoms can be reduced
(‘Success’) or not; in case of continued symptoms, the patient can experience re-operation
(‘Re-op’) or not within 5 years; in case of reoperation, the symptoms can be reduced
(‘Re-op success’) or not; regardless of symptom reduction, patients will experience OA
(‘long-term [LT] problem’) or not, which is evaluated 15 years after the initial intervention
in the model.
ATMP - D.Dubois
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12. Cost-utility analysis of ChondroCelect (CC) vs microfracture (MFX), base-case and additional scenarios (healthcare payer perspective)
ATMP - D.Dubois
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13. Acceptability curve of CC vs
Acceptability curve of CC vs. MFX, from probabilistic sensitivity analysis
The curve shows the proportion of cost-effective strategies depending
on the willingness-to-pay level.
CC is cost-effective in 80% of Monte-Carlo simulations if the payer has a willingness-to-pay
of 22,000 EUR/QALY.
ATMP - D.Dubois
4/23/2017