EBE-EFPIA Initiative Escher-ATMP Project Results Renske ten Ham, MSc Division of Pharmacoepidemiology and Clinical Pharmacology - Utrecht University
Escher-ATMP Project Overall Aim: Examine factors associated with successful ATMP development and commercialisation in Europe. Work package 1 Survey: Provide overview of product and developer characteristics and identify experienced challenges. Work package 2 Interviews: Substantiate the observed findings from WP1 by identifying challenge root-causes.
ATMP Landscape in Europe 271 Developers Identified 38% Survey Response ATMP Type 1% 1% Full cohort Respondents In 2016 65% of developers are SMEs, 35% are large developers. 53% 59% Gene Therapy Comb ATMP 46% 40% Cell based Therapy
ATMP Landscape in Europe 271 Developers Identified 38% Survey Response Developer Development Stage 41 In 2016 65% of developers are SMEs, 35% are large developers. Early Clinical Stage (phase I-II) 10 Late Clinical Stage (phase III) 6 7 Regulatory Approval Appl Product Com
Survey Results Experienced Challenges Grouped 100% 75% 50% 25% 0% Other HRM Clinical Financial Scientific Technical Regulatory 1 2 3 4 5 Top 5 Experienced Challenges MAA = Market Authorisation Application 16% Meeting Country Specific Requirements 15% Product Manufacturing 8% Clinical Trial Design 6% MAA Dossier Content Uncertainty 5% Quality Standards
Survey Results - Quotes IMPD needed research level ( ) because legislation was new and nobody had a clue how to do animal testing Slow CTA and GMO assessment Conducting regulatory roadshow to meet with regulatory bodies to understand requirements and obtain alignment For regulatory acceptance reasons the early stage clinical target group within the patient population differs from the final patient target group Lack of GMP grade raw materials Finding appropriate clinical investigation sites
Combining Survey Results with Interviews Many different challenging and facilitating factors identified in commercial EU ATMP development. Two elements causing many hurdles are: The disconnect between European (high level) regulation and national hurdles. Capabilities and business model at the start have effect throughout ATMP development success.
Disconnect between European (high level) regulation and national hurdles Commercial developers find European efforts so far helped ATMP development move forward. However, local interpretation and execution leads to many additional (duplicate) information requests, delays and increased cost. National Authorities have different interpretations of requirements for Clinical Trial Applications, Genetic Modified Organism legislation, Hospital Exemption and Good Manufacturing Practice. Inexperience and un-alignment are most mentioned. Small companies do not have the resources to address country specific requirements. Also, high data request burden drives preference of global developers to launch first in US or Asia.
Capabilities and business model at the start have effect throughout ATMP development success. ATMP development is much more complex than traditional drug development. Developers who start without (in-house) regulatory and quality expertise and business goals mostly aren t able to catch up, especially academic spin-off and SMEs. A realistic business model addresses at least the following factors: - Short and long term development goals - Regulatory and market access strategy - Realistic return on investment expectation and prediction Payers/HTA need to join regulators in interactions to decrease high perceived reimbursement criteria and uncertainty to maintain promise of growing EU ATMP market.
Concluding: Escher-ATMP project EU ATMP landscape is in early stages, shown by the majority of commercial developers who are in early clinical (phase I-II) product developmental stages. European efforts are very well received by developers. Compared, national authorities have not matured and need to bridge gaps between Europe and each other. More harmonization of CTA, GMO and GMP requirements between member states is needed to further advance EU ATMP development and compete with other international markets. ATMP development requires earlier planning and specialised skills compared to traditional drug development. Starting with a realistic business model and early regulatory and HTA involvement.
Concluding: Escher-ATMP project Stakeholder specific recommendations European Regulators: On the right track to shape European ATMP landscape, include local authorities and payers/hta in the process. Local Regulators: Need to bridge knowledge gap between national and European regulatory authorities. Country specific requirements are a major hurdle for developers. Payers/HTA: Need to collaborate with developers and regulators to address last major and mostly unaddressed hurdle. ATMP HTA and reimbursement is in its infancy. SMEs: Early on include GMP grade standards, regulatory and quality knowledge and build realistic business plan. Partnerships with experienced party to accelerate development and funding. Large companies: Most had same steep ATMP learning curve as SMEs but more experience in non- ATMP pharmaceutical development. Partner with SMEs to fill pipeline and accelerate innovation.
Acknowledgements Barbara Freischem Executive Director Esther Choi VC working group, BMS ATMP working group Dr. Andre Broekmans Executive Director Prof. Dr. Olaf Klungel Epidemiological Methods Dr. Jarno Hoekman Assistant Professor Dr. Anke Hövels Assistant Professor Prof. Dr. Marieke de Bruin Regulatory Science, Univ of Copenhagen Assistant professor, Utrecht University