Advanced Therapy Medicinal Products - ATMPs - A case study in health economics: ChondroCelect ATMP - D.Dubois 4/23/2017

A representative sample of the slides that will be presented and discussed during the course is displayed hereafter.

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 4/23/2017

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 4/23/2017

ChondroCelect First cell-based medicinal product authorized under the European ATMP framework (Regulation 1394/2007) ATMP - D.Dubois 4/23/2017

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 4/23/2017

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 1994... 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010... Year Outcome of 15 years of R&D > 500 patients treated till date ATMP - D.Dubois 4/23/2017 *EMA : European Medicines Agency

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 4/23/2017

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 4/23/2017 The American Journal of Sports Medicine , Volume 37 – Suppl. 1, November 2009

ATMP - D.Dubois 4/23/2017

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 4/23/2017

Cost-utility analysis of ChondroCelect (CC) vs microfracture (MFX), base-case and additional scenarios (healthcare payer perspective) ATMP - D.Dubois 4/23/2017

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