TOPRA Annual lecture

Regulatory Rapporteur

December 2023  |  Volume 20  |  No.11

Key points:

• Cell and gene therapies (C&GT) are at the teenage stage of growth, but their success is established already with significant value to patients, including long-term outcomes and potential cure.
• There have been exciting advances in the C&GT field with the CAR-T cell and gene editing revolutions; the future looks to gene editing, engineered cell and synthetic biology.
• New financing and reimbursement models are needed and jointly we have to ensure the sustainability of the field for the patient benefit.

Dr Miguel Forte started his lecture by describing the fantastic cell and gene therapies (C&GT) opportunity for patients and other stakeholders in the pharmaceutical industry; he described a complex business with significant investment and value to patient in oncology and rare disease.

The first gene therapy Luxturna was first approved in the US only six years ago (in 2017), and there are now 87 C&GT products approved globally, including 62 non-genetically modified cell therapies, 11 genetically modified cell therapies and 14 gene therapies. There is also a significant ongoing investment as 800 to 1,100 of each of these types of therapies were in development (pre-clinical to pre-registration) as of June 2023.

Forte shared key advances for C&GT, in particular gene engineering of cells for a therapeutic purpose, also referred to as adoptive cell therapies. He described engineering of Chimeric Antigen Receptor (CAR) T cells as a revolution for the field. While there are other adaptive cell therapies, CAR-T cells are currently by far the most studied with over 1,200 ongoing clinical trials. Gene engineering approaches have also been transformed with now 15 gene engineering approaches including viral, non-viral vectors and gene editing tools. In addition, there are exciting advances in manufacturing CAR-T cells, with potential for reduction of manufacturing time from typically more than six days to within 24 hours.

The difference in investment and number of clinical trials for C&GT were presented for the different regions with significantly higher investment in the US, and a higher number of clinical trials in Asia and US, compared to the EU. Forte highlighted the importance of increasing investment in EU and referenced the Clinical Trials Regulation (CTR) and Accelerating Clinical Trials (ACT) objectives of making the EU more attractive to increase the number of clinical trials in EU. The characteristics of C&GT clinical trials were also presented; these are typically open label, single arm and with no comparators, often with less than 100 patients and taking less than two years to complete.

Custom-made, personalised cell and gene therapies are significantly more expensive than other medicinal products prepared and prescribed for a broad population, however they are only administered once and have the benefit of long-term outcome and potential curative effect. As such, they were compared to transplants, which similarly require significant investment, but have anticipated durable benefits. The cost of C&GT treatment is therefore very high and new financing and reimbursement models are required to ensure the sustainability of the field for patient benefit.

The approval of new gene therapies may be at an inflexion point: while five gene therapies for rare genetic conditions were approved between 2017 and 2022, another five may be approved in 2023 alone. Forte believes that the future of C&GT is about gene editing, engineered cell and synthetic biology. In particular, he highlighted the editing revolution taking place for gene therapies with CRISPR, prime and epigenetic editing. Finally, most of the C&GT clinical trials are in oncology or rare disease, however it is expected that these therapies will be applied to other therapeutic areas affecting a broader population, such as cardiovascular disease.

Forte presented an exciting regulatory landscape which has already shown dynamic growth, but continues to hold exponential promise for broader populations.