Advanced Therapy Medicinal Products - ATMPs - A case study in health economics: ChondroCelect 110/17/2015 ATMP - D.Dubois.

Advanced Therapy Medicinal ProductsAdvanced Therapy Medicinal Products- ATMPs -- ATMPs -

A case study in health economics: ChondroCelect

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

ATMP’s

ATMPs include: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

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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

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ChondroCelectChondroCelect

First cell-based medicinal product

authorized under the European ATMP framework

(Regulation 1394/2007)

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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.

Active substanceActive substance

IndicationIndication

Controlled manufacturingQuality control

ImplantationBiopsy

ProductProduct

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ChondroCelect – ATMP development

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Underlying research(ECFA-Assay and ChondroCelect molecular markers)

Underlying research(ECFA-Assay and ChondroCelect molecular markers)

Pre clinical testing & validationPre clinical testing & validation

Phase III Clinical trialPhase III Clinical trial

Compassionate use in 370 patientsCompassionate use in 370 patients

Marketing authorization application at EMA*

Marketing authorization application at EMA*

EC ApprovalEC Approval

Year

2001 20021994... 2003 2004 2005 2006 2007 2008 2009

Outcome of 15 years of R&D > 500 patients treated till dateOutcome of 15 years of R&D > 500 patients treated till date

2010...

Post MA Follow-upPost MA Follow-up

*EMA : European Medicines Agency

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CC clinical evidence:superior structural repair at 12 months

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ChondroCelect

Microfracture

The American Journal of Sports Medicine , Volume 36, No 2, February 2008

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CC clinical evidence:superior clinical benefit over MF over 36 months

9 The American Journal of Sports Medicine , Volume 37 – Suppl. 1, November 2009

KOOS P-value

Overall(1) 0.048

Pain 0.044

Symptoms 0.123

Activity (ADL) 0.064

Sports 0.123

Quality of Life 0.036

Longitudinal analysis: treatment effect at 36m

(mixed linear model)

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Model structure – from model entry to OA onset after 15 years

During the 3 years following the knee intervention (microfracture [MFX] or autologouschondrocytes 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.

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Cost-utility analysis of ChondroCelect (CC) vs microfracture (MFX),base-case and additional scenarios (healthcare payer perspective)

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Acceptability curve of CC vs. MFX, from probabilistic sensitivity analysis

The curve shows the proportion of cost-effective strategies dependingon the willingness-to-pay level. CC is cost-effective in 80% of Monte-Carlo simulations if the payer has a willingness-to-payof 22,000 EUR/QALY.

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