The Latest Advances in Cell and Gene Therapy

By Dr. Priyom Bose, Ph.D.Reviewed by Lily Ramsey, LLM

The Current State of CGTs
Breakthrough Technologies 
Manufacturing Hurdles in CGT Development
Future Outlook 

Cell and gene therapies (CGTs) represent the cutting edge of drug discovery.¹ These are amongst the most advanced medical treatments, specifically designed to correct the root genetic cause of an underlying health issue. CGTs have the potential to revolutionize conventional treatment for a wide range of diseases that exhibit poor effectiveness.

Gene Therapy" />Image Credit: sdecoret/Shutterstock.com

The Current State of CGTs

According to the American Society of Gene & Cell Therapy (ASGCT) and Citeline, a total of 76 CGTs have been launched so far since the first product received approval from the global regulatory bodies in 2004.²

Although the majority of CGTs have been designed for the treatment of cancer and rare diseases, recently, researchers and pharmaceutical companies have focussed on other diseases as well. For instance, in 2023, new CGTs were launched by Lantidra and Elevidys to treat type 1 diabetes and Duchenne muscular dystrophy, respectively.^3,4

Based on the current estimates, the CGT market has been forecasted to reach over $40 billion by 2027. In recent years, more CGT products have been approved by global regulatory bodies, such as the US Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA).

Approximately, 10% of all new approvals by the FDA in 2023 were related to CGTs, which is a significant increase from 2021 and 2022.⁵ Similarly, the Catapult’s data also indicated a consistent rise in approved CGT products in the UK market, i.e., from 11 in 2023 to 14 in 2024.⁶

The 2024 annual review of the Cell and Gene Therapy Catapult highlighted that the UK remains an important market for developing and marketing new CGT.⁷ Recently, several new CGTs have been approved, including the treatment of hematological malignancies and hemophilia A.

Furthermore, the MHRA has become the first regulator globally to approve Casgevy (Vertex). This medicine uses the gene-editing tool, namely, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9), to treat β-thalassemia and sickle cell disease.⁸

Breakthrough Technologies

Advent and advancements in gene editing tools and cell therapy approaches, including autologous chimeric antigen receptor (CAR) T cell therapy, CRISPR-Cas9, and viral vector engineering strategies, have significantly contributed to rapid growth in CGTs.^9,10

These gene editing tools enable precise genetic modification with limited off-target effects, which has substantially increased therapeutic efficacy. Advancements in non-viral delivery systems offer a safer alternative to viral vectors that have significantly expanded gene therapy applications.

The implementation of artificial intelligence (AI) and automation have considerably transformed the landscape of CGT.¹¹ For instance, in comparison to traditional small molecule drugs, the process of manufacturing CGTs is incredibly complex because it involves the handling of live cells. Automation has effectively reduced the risk of contamination during biomanufacturing.

AI and automation have efficiently streamlined multiple complex steps involved in CGT development, such as cell extraction, genetic modification, expansion, purification, and formulation, before it is finally administered in patients.

Automation platforms enable consistent large-scale and small-scale production, which significantly contributes to the controlling of manufacturing costs. An increase in CGT production offers greater accessibility to both large patient populations and to niche groups.

Regulatory bodies, such as the U.S. FDA and the European Medicines Agency (EMA), are accelerating approvals for CGT clinical trials.¹² New regulatory frameworks, such as the FDA’s accelerated approval pathways and Regenerative Medicine Advanced Therapy (RMAT) designation, have reduced the timelines for potential CGTs.

A surge in investment and funding has also contributed to the increase in CGT production. For example, large pharmaceutical companies and venture capital firms have been heavily investing in CGT companies, which enables more clinical trials and expansion of manufacturing capacities.

A study by the Alliance for Regenerative Medicine (ARM) highlighted that CGT investment reached record levels in 2024. Increased awareness about the efficacy of CGT has drawn more patients with rare genetic diseases and cancers to participate in clinical trials.

Manufacturing Hurdles in CGT Development

CGTs are expensive to develop. Researchers have estimated that more than $1.9 billion could be required to design and bring a new CGT to market.¹³ Many research and development (R&D) projects struggle to obtain finance for CGT development.

Besides financial barriers, CGT companies also experience difficulty in product commercialization, which is pivotal for patient acceptance.

The current manufacturing process fails to meet the demands for CGTs, producing a huge gap between production and patient needs.¹⁴ The recent transformation of biomanufacturing companies from adopting semi-automated solutions to fully automated cell therapy manufacturing processes could effectively meet the demand.

Automation could considerably reduce the need for human intervention and decrease the risk of contamination.

CGTs have a shorter shelf-life compared to conventional medicines. Considering this, new regulatory policies promoting point-of-care manufacturing have been developed in the UK.

Future Outlook

In the future, scientists must focus on harnessing new technologies to reduce the manufacturing cost of CGTs.

A reduced CGT cost will also increase its utility to many patients belonging to different socio-economic backgrounds. The development of appropriate infrastructure and skills will help improve CGT production, which will help pharmaceutical companies meet the current demand.

Academic and industry stakeholders in the CGT sector may collaborate to build more training facilities and develop a strong workforce made up of a diverse pool of candidates.

Key stakeholders can come together to increase general awareness of CGTs, which could build a strong base as the industry prepares to commercialize more therapies.

References

1. Chancellor D, et al. The state of cell and gene therapy in 2023. Mol Ther. 2023;31(12):3376-3388. doi: 10.1016/j.ymthe.2023.11.001.
2. Gene, Cell, & RNA Therapies Landscape Report, Q2 2024 Quarterly Data Report. American Society of Gene & Cell Therapy. Citeline. 2024; Available at: https://www.asgct.org/global/documents/asgct-citeline-q2-2024-report.aspx
3.  Duan D. Duchenne Muscular Dystrophy Gene Therapy in 2023: Status, Perspective, and Beyond. Hum Gene Ther. 2023 34(9-10):345-349. doi: 10.1089/hum.2023.29242.ddu.
4. Parums DV. Editorial: First Regulatory Approval for Allogeneic Pancreatic Islet Beta Cell Infusion for Adult Patients with Type 1 Diabetes Mellitus. Med Sci Monit. 2023;29:e941918. doi: 10.12659/MSM.941918
5. Fermaglich LJ, Miller KL. A comprehensive study of the rare diseases and conditions targeted by orphan drug designations and approvals over the forty years of the Orphan Drug Act. Orphanet J Rare Dis. 2023;18(1):163. doi: 10.1186/s13023-023-02790-7.
6. Kakkaiyadi, K. Cell and gene therapy companies can shape the UK’s industrial strategy. 2024; Available at: https://www.pinsentmasons.com/out-law/analysis/cell-gene-therapy-companies-uk-industrial-strategy
7. Cell and Gene Therapy Catapult. Annual Review 2024. Available at: https://cgt.ams3.cdn.digitaloceanspaces.com/Cell-and-Gene-Therapy-Catapult-Annual-Review-2024.pdf
8. Parums DV. Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia. Med Sci Monit. 2024;30:e944204. doi: 10.12659/MSM.944204.
9. Rossi M, Breman E. Engineering strategies to safely drive CAR T-cells into the future. Front Immunol. 2024;15:1411393. doi: 10.3389/fimmu.2024.1411393..
10. Xu CL, et al. Viral Delivery Systems for CRISPR. Viruses. 2019;11(1):28. doi: 10.3390/v11010028.
11. Ludwig J, Mcintosh J. Simplifying CGT: A Necessary Precursor to Integrating AI and Automation. 2023; Available at: https://pharmaceuticalmanufacturer.media/pharmaceutical-industry-insights/latest-pharmaceutical-manufacturing-industry-insights/simplifying-cgt-a-necessary-precursor-to-integrating-ai-and-/
12. Ammar D, et al. Accelerating development of engineered T cell therapies in the EU: current regulatory framework for studying multiple product versions and T2EVOLVE recommendations. Front Immunol. 2023;14:1280826. doi: 10.3389/fimmu.2023.1280826.
13. Sabatini MT, Chalmers M. The Cost of Biotech Innovation: Exploring Research and Development Costs of Cell and Gene Therapies. Pharm Med. 2023; 37, 365–375. doi.org/10.1007/s40290-023-00480-0
14. Mireku A. Cell and gene therapy companies trip at scalability hurdle. 2024. Available at: https://www.pharmaceutical-technology.com/features/cell-and-gene-therapy-companies-trip-at-scalability-hurdle/

Further Reading

• All Drug Discovery Content
• Hit to Lead (H2L) Process in Drug Discovery
• Understanding Lead Optimization
• How is AI Transforming Drug Discovery?
• Hot Melt Extrusion in the Pharmaceutical and Food Industries