(CSPOT44) Planned and Ongoing EMA-mandated Post-approval Observational Studies of Cell & Gene Therapies (CGT): What Can We Learn from Study Characteristics?

Background: Cell and gene therapy products (CGTs) can include gene therapy, cell therapy, and tissue-engineered medicines. We have also included small interfering ribonucleic acid (siRNA) therapies. Since CGTs aim to create a permanent/long-lasting change in the patient’s body, this may directly or indirectly lead to long-term increased risk of adverse events, which may not be anticipated prior to approval of the CGT. Observational post-approval studies can help assess long-term safety, effectiveness and durability of CGTs.

Objectives: To provide an overview of key design characteristics of planned and ongoing observational CGT studies that were required by the EMA, and which reported “risk assessment” as one of the study scopes.

Methods: We conducted a search of planned/ongoing (as of JAN 2024) EMA-mandated post-approval studies using a EU register/platform of non-interventional studies (EU PAS Register) and identified 174 potential studies. We manually reviewed these study entries to identify those which included a CGT. Of the CGT studies identified, we manually extracted study design characteristics.

Results: Of the 174 studies, 17 assessed CGTs.

Of the 17 CGT studies, 6 involved cell therapy, 5 involved gene therapy, 5 involved siRNA, and 1 involved tissue-engineered medicine. More than half were first registered in the last 3 years (n=12), and the range for year of first registration was 2013 to 2024.

All of the studies aimed to assess real-world safety of the CGT. Often, but not always, selected events of interest were specified as study outcomes. Many of the studies also specified subpopulations of interest. Only four of the studies reported patient quality of life as one of the study outcomes.
The most common length of planned follow-up was 15 years (n=8), 2 planned 10 years, and 6 planned 5 years or less of follow-up. The median size was 300 patients. The majority (n=11) planned 100-500 patients. Approximately half of the studies were restricted to adults only (n=9), while the rest allowed for both pediatric and adult ages.

The majority reported that they were not planning to use an established data source (n=10). Approximately half (n=8) reported only one type of data source. 14 studies reported at least one of their sources of data as “Prospective patient-based data collection”, 6 of which reported it as the only source of data. 6 studies reported “disease/case registry” as one of their sources of data, none of which reported it as the only source of data.

Conclusions: In the last few years, the number of planned/ongoing observational CGT studies, that were mandated by the EMA and which include risk assessment as a reported study scope, has increased considerably. Further understanding of these studies may help guide design and execution of future CGT studies.