Advanced Therapy Medicinal Products (ATMPs), which include cell and gene therapies and tissue engineered products, are a group of innovative products targeting diseases and conditions for which there are few, if any, effective treatments. The success of the first CD19 chimeric antigen receptor T cell (CAR T) products Kymriah and Yescarta against B-cell malignancies has raised the awareness of the high potential of ATMPs, but also shown the several challenges relating to their clinical use1. One of these challenges is the high prices asked by the manufacturers of these products, which are not always supported by national pricing and reimbursement bodies2.
In such cases, the discrepancy between a regulatory approval and a negative decision from a health technology assessment (HTA) body has raised concerns and questions from industry about how to ensure that an approved product also gets to the market and to patients. Many jurisdictions have created early access schemes and ways to communicate with regulatory and HTA bodies early on to ensure successful outcomes of both reviews3. However, the ATMP industry is facing challenges in both aspects.
The development of ATMPs has substantially increased with a focus on clinical trials in recent years. Several cell and gene therapy products have been authorised worldwide, most recently the CAR T product Tecartus from Kite Pharma Inc.4 in the US and Zolgensma for spinal muscular atrophy (SMA)5 in the EU.
Today there are more than 980 developers globally, the majority (78%) of whom are in North America and Europe.6 Over 1,000 clinical trials were underway worldwide at the end of 2019, two-thirds of which (64%) were in Phases 2 and 3. There has been a clear shift from early to late phase trials, as only four years earlier the majority of trials (> 90%) were in Phases 1 and 27. Since beginning of 2015, the overall number of ATMP clinical trials and ATMPs in Phase 3 has doubled, suggesting multiple new ATMPs will be approaching the marketing authorisation application stage in the next few years.
Today, the focus of ATMP development is heavily in gene therapy and genetically modified cells which constitute three-quarters of products in clinical trials. This is most probably due to the fast development of novel vectors and technologies, including genome editing. In addition, a lot of safety data has accumulated for certain gene therapy approaches (e.g. adeno associated virus vectors, AAV and lentivirus vectors, LVV), which reduces the regulatory burden before first clinical trials.
From an indication perspective, the majority of ATMP clinical trials (657/1066, 62%) 6 are in oncology, including leukaemia, lymphoma, and solid tumors, which may be explained by the great interest towards novel immunotherapies using genetically modified cells. In 2019, genome edited cells using the CRISPR/Cas9 approach proceeded to clinical trials both in the US and the EU8 and the first results from a trial studying an induced pluripotent stem (iPS) cell-derived product were reported in the EU 9.