Background
Advanced therapy medicinal products (ATMPs) such as gene and cell-based therapies are highly innovative medicines that provide new opportunities to treat conditions with high unmet medical need. It is often described that the characteristics of advanced therapies are considerably different from more conventional medicines such as small molecules or biologicals. Differences lay in their mechanism of action, live raw materials, intended function and manufacturing. In addition, ATMPs consist mostly of live cell and tissue materials.
The number of ATMPs stranded during (clinical) development is unknown but perceived as considerable given the contrast between high clinical activity and low number of products reaching advanced (regulatory) development milestones. Research has highlighted that ATMPs experience several clinical, regulatory, and economical challenges, more so than more conventional medicinal products. It is also observed that most ATMP-developers are not companies but hospitals, academic facilities, and so-called small and medium enterprises (SMEs); higher compared to the small-molecule and biotechnology industry.
RSNN has previously brought together stakeholders that are involved in ATMP development and discussed hurdles in bringing advanced therapies to patients, emphasizing the role of the national hospital exemption (HE) procedures. However, substantial regulatory questions remain unanswered, in and outside of HE. Examples are safety and quality concerns due to loss of centralized overview of ATMP development (in part due to HE), implications of acceptance of less complete evidence packages for marketing authorization (e.g., for conditional marketing authorization) for downstream assessment, constructive interactions between stakeholders, organizational learning. These questions require additional, tailored investments in terms of research and discussions to answer them.
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What are ATMPs?
The European Medicinces Agency (EMA) provides a general overview on ATMPs, guidance on their development, and their classification. On a national level, the Health and Youth Care Inspectorate (‘Inspectie Gezondheidszorg en Jeugd’ in Dutch) also provides general information on ATMPs and information on clinical research with ATMPs.
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Which regulatory routes exist for ATMPs to reach the patients?
As a rule, a European marketing authorisation granted by the EMA is required before an ATMP treatment can be applied outside a research environment. An exception may be made in certain situations, such as the for the ‘hospital exemption’ procedure. More information provided by the EMA on the marketing-authorisation procedures and the requirements for ATMPs can be found here. Similarly, the Health and Youth Care Inspectorate provides information on authorisation of ATMPs here.
This topics has been discussed in the RSNN - RSNN Expert Meeting Report - The route for ATMPs from bench to bedside.
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ATMP products
An overview of the ATMPs that have been submitted for Marketing Authorization Application (MAA) at the EMA are being displayed in this document. The document provides information on each ATMP regarding brand name, active substance, indication, MAA assessment, and authorisation status. The document has been composed by Eleanor van Dijk. The information has been updated until 30 June 2022.
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Reports
- EC & EMA European Commission DG Health and Food Safety and European Medicines Agency Action Plan on ATMPs (2017)
- EMA – CAT Reflection paper on stem cellbased medicinal products (2011)
- EMA Report from the CAT expert meeting on scientific and regulatory considerations for adeno-associated viral vector (AAV)-based gene therapy (2018)
- EMA – Outcomes of the multistakeholder advanced therapy medicinal products (ATMPs) expert meeting: exploring solutions to foster ATMPs’ development and patient access in Europe (2016)
- EMA - EMA warning against using unproven cell-based therapies (2020)
- KWF – Cel en gentherapie naar de oncologische klinische praktijk: Kansen en knelpunten voor innovatie vanuit de academie (2021)
- LERU - Advanced Therapy Medicinal Products (2019)
- LUMC – Advanced Therapy Medicinal Products (ATMPs) naar de reguliere klinische zorg: Knelpunten en Mogelijkheden (2016)
- RIVM – De toekomstverwachtingen over ATMPs (2018)
- RSNN - RSNN Expert Meeting Report - The route for ATMPs from bench to bedside (2021)
- VWS – Kamerbrief met stand van zaken geavanceerde therapieën (2022)
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Patient organizations
- Hematon
- Nederlandse Federatie van Kankerpatiënten organsiaties (NFK)
- Stichting Melanoom
- Patient alliance for rare and genetic diseases (VSOP)
- Nederlandse Vereniging van Hemofilie-Patiënten
- Volwassenen Kinderen en Stofwisselingsziekten (VKS)
- Vereniging Spierziekten Nederland
- Vereniging Kinderkanker Nederland
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Private developers
- Amylyx
- Avexis
- Biogen
- Celgene
- Gilead
- HollandBIO (branch organization)
- Janssen
- Kiadis Pharma
- Kite Pharma
- Novartis
- Pfizer
- Roche
- UniQure
- VIG (branch organization)
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Academic developers
- Amsterdam UMC
- Erasmus MC
- Hovon
- LUMC
- Maastricht UMC+
- NKI/AVL
- Princes Maxima Centrum Utrecht
- RadboudUMC
- Sanquin
- UMCG
- UMC Utrecht
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Regulatory authorities/government bodies
- Central Committee on Research Involving Human Subjects (Centrale Commissie Mensgebonden Onderzoek)
- Loket Gentherapie
- Health and Youth Care Inspectorate (Inspectie Gezondheidszorg en Jeugd)
- Medicines Evaluation Board (College ter Beoordeling van Geneesmiddelen)
- Ministry of Health, Welfare and Sport (Ministerie van Volksgezondheid, Welzijn en Sport)
- National Health Care Institute (Zorginstituut Nederland)
- Committee for Advanced Therapies (CAT), The European Medicines Agency (EMA): The EMA provides information on the marketing-authorisation procedures for advanced-therapy medicinal products and offers support for advanced-therapy developers.
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Initiatives
- DARE NL: Dutch platform for cancer-specific ATMP Research to ensure harmonized development, clinical testing and sustained patient access (2022 - ongoing)
- ATMP Course Directory with ATMP educational resources and events
- CURE4LIFE: Development and societal impact of stem cell based genetic medicines (2022 ongoing)
- ICAT – Utrecht Innovation Center for Advanced Therapies
- NecstGen
- RegMedXB
- reNEW
- T2EVOLVE: Accelerating development and increasing awareness and accessof patients with cancer to immunotherapy
- Alliance for Regenerative Medicine (ARM)
- National Health Care Institute (Zorginstituut Nederland) Horizonscan Medicines
- DARE NL: Dutch platform for cancer-specific ATMP Research to ensure harmonized development, clinical testing and sustained patient access (2022 - ongoing)