Background: Advanced Therapeutic Medicinal Products (ATMPs) offer innovative treatments for various congenital, malignant, and other diseases and/or tissue injuries, leveraging genes, tissues, or cells.1 Most ATMPs have originated in the U.S. and China, while Europe lags behind in early development, speed of clinical trials & regulatory approval and in manufacturing. The EU-funded JOIN4ATMP project aims to address these hurdles and join forces fostering ATMP development to expand therapeutic options and patient access in Europe.2
Aims: One aim of JOIN4ATMP is to identify and collect preclinical testing strategies used in ATMP development in Europe and assess their predictive value for safety and efficacy. Beyond animal studies, the project evaluates alternative methods, including 2D/3D tissue models and computational approaches like artificial intelligence and machine learning. This will inform recommendations for preclinical ATMP testing strategies in Europe.
Methods: To map the European ATMP landscape, we developed a database of clinical ATMP trials, with data extracted from the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT database). Using a Python script, trials self-classified as ATMPs were extracted and categorized by phase (EMA-approved [category A], PhI/I-II [category B], PhII [category C]) and therapy type (gene therapy, tissue, somatic, combination ATMP, other). False positives were manually filtered.
Results: Of 43,989 registered clinical trials (as of August 2024) in the European Union Clinical Trials Register (EU CTR), 727 related to ATMPs were identified with PhI, I/II, II studies performed in Europe (Fig. 1). Of these, 47 trials involved ATMPs that by now have received market authorization by EMA (A). Among the PhI/I-II studies (B, n=347), gene therapies were predominant (n=173 gene therapies; n=30 tissues; n=107 somatic cells; n=7 combinations; n=30 studies could not be clearly categorized according to EudraCT online entry). 333 trials were PhII studies (C). To analyze hurdles and challenges experienced during ATMP development in Europe, we initially focus on group B – PhI and PhI/II studies. Next, this database will be manually reviewed to identify those with European preclinical development and FIH studies, excluding entries that are either falsely categorized as ATMPs (e.g. DNA/ RNA based vaccines against infectious diseases), have a pure observational context or involve only companion diagnostics. During this manual selection of trials of relevance, we are extracting all basic and regulatory information available online. The database will serve to connect with ATMP developers for surveys and semi-structured interviews.
Conclusion: ATMP development in Europe lags behind other regions, potentially due to regulatory hurdles. This JOIN4ATMP subproject aims to build a comprehensive database to analyze these barriers and share successful strategies, ultimately guiding European ATMP developers on predictive preclinical testing for clinical safety and efficacy.