Background:
Advanced Therapeutic Medicinal Products (ATMPs) represent innovative treatments for various diseases and tissue injuries, utilizing genes, tissues, or cells.1 Despite their potential, Europe lags behind in the early development of ATMPs. The EU-funded JOIN4ATMP project aims to identify challenges in ATMP development and to propose possible solutions.2 One of the objectives is to implement a database of clinical ATMP trials conducted in Europe, providing an overview of available therapies.
Methods:
To develop a database of all the clinical ATMP trials conducted in Europe with data from the European Union Clinical Trial Register (EU CTR), we used a Python script to extract all the trials that self-classified them as ATMPs. Next, they were categorized by their phase (EMA-approved ATMPs, Phase I or Phase I/II, Phase II) and their therapy type (gene therapy, tissue-engineered medicines, somatic cell therapy, combination ATMPs, others). Initially, the focus was on gene therapy medicines by collecting data like the ATMP identifier, the target disease and the disease category with online research of basic information available. Nevertheless, the same methodology will later be applied for the other ATMP categories.
Results:
Of 43,989 registered clinical trials (as of August 2024) in the EU CTR, 727 ATMP-related studies were found with Phase I, I/II and/or II studies performed in Europe. Of these, 49 trials involved EMA-approved ATMPs. Phase I and Phase I/II studies were sub-classified. Among these trials (n=342), gene therapies were most common (n=169), followed by somatic cells (n=107), tissues (n=30) and combinations (n=7). 29 studies could not be clearly categorized according to EudraCT online entry and therefore need to be classified manually. 336 trials were Phase II studies. To analyze potential hurdles and challenges experienced during preclinical ATMP development in Europe, our initial focus are Phase I and Phase I/II studies, starting with gene therapy medicines. Among the 169 trials on gene therapies extracted from the register, 110 had preclinical studies performed in Europe. Fifty of these trials targeted cancer with their therapy, 57 focused on rare diseases and only 3 of them seemed to be developed for common diseases. For 54 studies, database entry suggests that the preclinical development of the ATMPs was conducted outside of Europe, mainly in the USA. Another 5 studies seemed to be falsely classified as ATMPs. These findings form the first step of implementing a comprehensive ATMP database. The next steps include the same analyses for the other ATMP categories and compiling detailed information sheets for each ATMP.
Conclusions:
While Europe conducts and participates in an increasing number of ATMP-related studies, a comprehensive overview of the landscape is lacking. It appears, that many ATMPs developed outside Europe reach European patients only at later stages of development (≥phase II). Moreover, it appears that ATMPs developed and entering Phase I in Europe only rarely reach market authorization. The JOIN4ATMP subproject aims to implement a comprehensive database to get an overview to further analyze the studies regarding possible barriers and share successful strategies on preclinical testing.