The review was released by CGT Catapult, a center of excellence in the UK that provides cell and gene therapy relevant clinical, process development, manufacturing, regulatory, health economics and market access expertise.
Industry backed trials are now accounting for approximately 75% of all advanced therapy medicinal product (ATMP) clinical trials in the UK. “The majority of these commercially sponsored trials are backed by non-UK based companies demonstrating the appeal of the UK ecosystem for these types of trials due to the regulatory environment and scientific and clinical expertise available.”
The report also noted that the ongoing activities of the Advanced Therapy Treatment Centers network, funded by the UK government Industrial Strategy Challenge Fund, continues to support the development of the UK infrastructure for clinical adoption of ATMPs. “This network has been successful in building systems within the NHS to ensure that products progress effectively through clinical development and can be commercialized in the UK to reach patients.”
CGT Catapult said the overall growth in the number of ATMP clinical trials in 2020 may imply that the onset of COVID-19 and the pressures it caused on the healthcare system have not had an impact on this industry.
However, as the UK watchdog, the Medicines and Healthcare products Regulatory Agency (MHRA), does not need to be notified of interruptions to trials due to COVID-19, the true impact of the pandemic on all stages of clinical trials may not be yet fully ascertained, it added, with the impact only “likely to become more apparent in clinical activities over the next two to three years.”
Breakdown of trials by phase
The publication saw the highest increase in Phase II trials; they grew by 42% in 2020, followed by a 27% increase in Phase III trials, a 20% increase in Phase I/II trials, and a 19% increase in Phase I trials. “We are also reporting an additional Phase IV clinical trial.”
Vector usage trends
The majority of the biological medicine product trials in the UK are employing viral vector mediated gene transfer, with an even distribution between in vivo and ex vivo gene delivery method, according to the review.
Adeno associated virus (AAV) and lentiviral vectors are the most common in vivo and ex vivo gene delivery vectors, respectively.
"For in vivo gene therapy clinical trials, we note that AAV based vectors remain the main vector of choice (81%) with a small proportion of trials using adenovirus (5%), lentivirus (4%), or non-viral vectors (5%). For ex vivo clinical trials, the use of lentiviral vector delivery dominates (68%), followed by retroviral vectors (22%). In 2020, we also see an emergence of non-viral ex vivo based gene therapies, which accounted for 5% of ATMP trials observed.
“The ex vivo vectors are predominantly used for CAR-T based therapies (CAR-T and CAR-T + gene editing), which account for 47% of ex vivo clinical trials. This is followed by gene corrections/insertion therapies, which account for 42%. The ex vivo CAR-T and TCR based clinical trials almost exclusively focus on oncology, whilst gene corrections focus on multiple disease types.”
The cell types investigated in ATMP clinical trials remain largely unchanged from 2019. T-cells continue to be the dominant cell type, accounting for 44% of UK ATMP clinical trials. “This is as expected since research into oncology, the largest therapeutic area, is largely T-cell focused, and is consistent with previous years.”
Increasing focus on metabolic diseases
Oncology remains the main therapeutic area accounting for 35% of the overall UK ATMP trials ongoing, followed by ophthalmology (12%) and hematology (12%), said the authors.
Similarly, of the trials initiated in 2020, oncology was the largest therapeutic area with hematological indications (19%) and metabolic diseases (18%) being the second and third largest therapeutic areas targeted. “This increase in clinical studies targeting metabolic diseases potentially suggests an emerging therapeutic area targeted by ATMPs.”
Somatic cell therapy space lags
Gene therapy trials currently account for 70% of the ATMP clinical trials in the UK, somatic-cell therapies account for around 20% of such investigations, whilst tissue engineered therapies make up the remaining 10%, finds the review.
Of the gene therapy studies, there is a fairly even split between ex vivo (53%), which includes CAR-T and transduced hematopoietic stem cell derived products, and in vivo (47%) genetic modification.
Whilst there has been an increase in the number of all ATMP clinical trials for both autologous and allogeneic therapies, the proportion of autologous to allogeneic products has remained consistent throughout the years, with approximately 70% being autologous and 30% allogeneic, said the authors.
Overall, the majority of UK ATMP clinical trials are currently recruiting (53%) or in follow-up (26%). “The proportion of trials in recruitment for somatic-cell therapies is significantly higher than for gene therapies and tissue engineered therapies. This suggests that the somatic cell therapy space is not as mature as the gene therapy space.”
The growth seen in 2020 of Phase III and IV trials is indicative of the ATMP space maturing and sponsors progressing though their clinical development programs, with the approaching long-term safety studies, continued the review.
"Additionally, many new umbrella trials have started, which group together long-term safety follow-ups on various trials where subjects have been exposed to the same therapy. In the coming years, it is likely that the greatest impact on trial status will be these trials having longer follow-up periods."