Cell and gene therapy (CGT) is a new biomedical method that uses cell and gene technology to treat or prevent diseases.
The latest studies have shown that CGT technology has shown good clinical prospects in the treatment of hereditary diseases, cancers and certain viral infectious diseases, especially in the fields of cancer and rare diseases. With the continuous advancement of technology and the expansion of clinical applications, the field of CGT is booming with unprecedented innovation vitality.
Based on part of the contents of the Blue Book on the Status and Future Trends of the CGT Industry, this article provides an in-depth analysis of the innovation trends in the field of CGT, and discusses the latest progress made in broadening indications, innovating treatment strategies, and optimizing cost control and payment models, providing readers with a comprehensive and in-depth perspective.
1. The application field of CGT continues to expand: to solid tumors, infectious diseases, and chronic diseases
The application field of CGT has expanded from rare diseases and hematologic tumors to solid tumors, infectious diseases, and chronic diseases. The potential of CGT is being explored, from an initial focus on hereditary rare diseases and hematologic malignancies such as hemophilia, leukodystrophy and B-cell lymphoma, to solid tumors, chronic diseases and infectious diseases.
Tumors and infectious diseases account for a significant proportion of gene therapy clinical trials in the world and in China, indicating that the application boundaries of CGT are constantly expanding. For example, the exploration of the treatment of chronic diseases such as diabetes and cardiovascular diseases, as well as infectious diseases such as AIDS, is becoming a research hotspot, indicating that CGT is moving towards diversified therapeutic areas.
2. Innovation of CGT treatment strategy: universal, multi-target and combination therapy
1. CGT industry development challenges
While cell and gene therapy has shown great therapeutic potential, it will take many challenges to realize its broad application and commercial potential, including technological innovation, regulatory environment, production costs, payment mechanisms, and ethical and social acceptance.
(1) Effectiveness challenges
(1) Targeted delivery efficiency: It is key to ensure that the therapeutic gene or cell accurately reaches and acts on the target cell or tissue. Currently, efficient and specific delivery systems remain a challenge, especially for targeting non-dividing cells or deep tissues.
(2) Persistence and expression control: In some cases, gene therapy requires long-term stable gene expression to maintain therapeutic efficacy, while in other cases, controllable gene switches may be required to modulate therapeutic activity, which requires precise gene regulation mechanisms.
(3) Immune response: The patient's immune rejection of transgenic cells or vectors may affect the effectiveness of treatment, and strategies are needed to reduce or manage this response.
(2) Security challenges
(1) Off-target effects: Gene editing technologies such as CRISPR may lead to accidental editing of non-target genes, causing potential safety issues and requiring more precise and specific editing tools.
(2) Carcinogenic risk: Gene insertion may activate proto-oncogenes or interfere with tumor suppressor genes, increasing the risk of cancer, and adequate risk assessment is required before treatment.
(3) Long-term side effects: As the long-term effects of CGT are not fully understood, long-term monitoring and research are necessary to ensure that there are no unforeseen health consequences.
(3) Cost challenges
(1) High treatment costs: The personalized customization, complex production process and strict quality control of CGT lead to extremely high treatment costs, which are unaffordable for most patients.
(2) Large-scale production problems: The production of cell and gene therapy products often requires a high degree of customization, which makes it difficult to achieve the large-scale production efficiency of traditional drugs, which increases costs.
(3) Payment and reimbursement mechanism: The existing medical insurance and reimbursement system has not fully adapted to the high cost characteristics of CGT, and how to establish a reasonable payment model to ensure patient accessibility is a major problem.
and (4) ethics and social acceptance
(1) Ethical considerations: Gene editing, cell therapy and other technologies touch on human genetic material, which has triggered extensive discussions on ethical issues such as gene privacy and gene-edited babies.
(2) Public awareness: Improving the public's understanding and trust in CGT technology and reducing misunderstandings and fears is an important part of promoting the healthy development of the field.
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2. CGT R&D strategy
In the field of cell therapy, innovative technologies such as universal CAR-T, multi-target CAR-T, and immune cell combination therapy are emerging.
Universal CAR-T (UCAR-T): It has the advantages of industrial mass production, short cycle time and low cost, and can solve various problems of customized CAR-T, such as off-target toxicity, cytokine storm and other safety issues, as well as complex preparation process, T cell failure, limited indications and high cost. The emergence of universal CAR-T therapy will greatly promote the popularization and application of CAR-T therapy.
Multi-target CAR-T: It can effectively avoid tumor recurrence caused by antigen escape and improve the efficiency of cell therapy. For multiple targets, multi-target CAR-T can overcome the problems of easy loss of a single target, decreased response, and negative impact of heterogeneous cells, and improve the therapeutic effect.
Immune cell combination therapy: Combining immune cells (such as CAR-T, NK, macrophages) with monoclonal antibodies/bispecific antibodies can greatly improve anti-cancer efficiency. In addition, stem cell combined immunotherapy has also shown great potential, by differentiating stem cells in vitro into immune cells such as CAR-T, NK, DC, etc., and then infusing them back into patients, to achieve large-scale mass production, reduce costs, and reduce the steps of patient autologous cell extraction and production.
Third, cost reduction and innovative payment models go hand in hand
In the face of the high cost of treatment at CGT, cost reduction and innovative payment models have become the direction of joint efforts within and outside the industry:
1. CGT cost reduction path
(1) The general-purpose CAR-T can reduce the total cost of consumables from $60,000 to $2,000, and the QC cost from $30,000 to $1,000, thereby reducing the production cost from $95,780 to $4,460 for a custom CAR-T.
(2) Stem cell combined with immunotherapy can also achieve large-scale mass production and reduce costs.
(3) CRO/CDMO can also effectively reduce costs.
2. Explore innovative payment systems for CGT
(1) The United States has introduced payment policies related to CAR-T therapy, and in 2021, it is proposed to include CAR-T cell therapy products in DRG package payment, create a new MS-DRG, and use the mechanism of DRG payment "surplus retention, excess self-responsibility" to effectively control the treatment cost of CAR-T products and reduce the burden on patients.
(2) In Japan, the payment model of CAR-T therapy is based on the patient's age and clinical benefits, and the patient pays 10%-30% on the basis of medical insurance payment, and the specific payment amount can be reduced to about 410,000 yen.
(3) Up to now, 5 CAR-T models have been approved for marketing in China, the price of BCMA is as high as 1.166 million yuan/needle, and the price of Yikaida ®, Carteyda ®, and Yuanruida ®, which target CD19, is as high as 1.2 million yuan/needle, 1.29 million yuan/needle, and 999,000 yuan/needle, respectively, all of which have not yet entered the medical insurance catalog, and there is still a long way to go for CAR-T therapy to be truly implemented for patients.
Information query of CAR-T therapies approved for marketing in China
Image source: Yaorong Cloud Global Drug R&D Database
(4) At present, commercial insurance, such as Taiping Life, Ping An Life, Xinhua, Zhong'an and other insurance institutions have included CAR-T therapy into the scope of protection, and at the same time, millions of medical care can reimburse CAR-T therapy drugs, such as Huimin Insurance, as well as millions of medical insurance, high-end medical insurance, special drug insurance, etc. Fosun Kite, JW Therapeutics, and Innovent Biologics/IASO Biologics have all blazed new trails outside of medical insurance and actively tried various innovative payment methods to solve payment problems and improve access to medicines.
Epilogue:
The field of CGT is undergoing a profound transformation, from the expansion of therapeutic areas, the innovation of treatment strategies, to the innovation of cost control and payment models, and every step of progress indicates that this cutting-edge technology is gradually maturing and bringing the dawn of cure to more patients. In the future, with the continuous breakthrough of technology and the continuous optimization of the policy environment, CGT is expected to open a new era of precision medicine and become an important weapon for mankind to fight diseases.
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