Cell and gene therapy represented by CAR-T therapy has become a prairie prairie

CAR-T therapy is a typical representative of cell and gene therapy (CGT), and it is also the most mature cell therapy at present.
It has shown amazing therapeutic effects in the treatment of lymphoma and multiple myeloma
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As of the end of March, there are 7 CAR-T drugs that have been listed or BLA (Biologics License Application) in the world (Yescarta and Yikaida are one), but CAR-T therapy is only one kind of CGT, the author will sort it out for you Take a look at the CGTs that could lead to the next generation of therapeutic technologies
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CGT is a method of transducing exogenous therapeutic genes into cells using gene therapy vectors, and then changing the original gene expression of cells and treating diseases through the transcription and translation of exogenous genes
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It is mainly divided into cell therapy and gene therapy
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The main forms of CGT products include gene therapy vectors, oncolytic virus products, cell products (such as CAR-T, NK cells),
etc.
Cell therapy mainly involves in vitro treatment.
The patient's cells are modified in vitro and then returned to the patient to achieve the therapeutic effect.
The typical representative is CAR-T therapy
.
Gene therapy mainly involves in vivo therapy, introducing foreign genes into target cells in patients, and then treating the expression of regulatory proteins at the gene level, so as to achieve the purpose of treating diseases
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In vivo therapy mainly relies on non-viral or viral vectors to transfer functional genes into host cells.
Commonly used non-viral vectors include polymer micelles, lipid particles, plasmids, etc.
, and commonly used viral vectors include adenovirus, adeno-associated virus (AAV), Retroviruses, lentiviruses,
etc.
01 A variety of CGT drugs are listed at home and abroad The development of CGT is closely related to the development of basic sciences such as molecular biology and genomics
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It can be traced back to the DNA double helix structure proposed in 1953 and the concept of gene therapy was first proposed in 1972, and the CGT industry has continued to develop
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In 2003, the world's first gene therapy drug recombinant human p53 adenovirus injection (Jinshengsheng) was approved in China, and many subsequent CGT products were approved one after another
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At present, the FDA has approved 2 viral vector therapies (Zolgenmsa and Luxturna) and 1 oncolytic virus therapy (Imlygic) in addition to the 6 CAR-T drugs that have been approved, and two CAR-T drugs have also been approved in China
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02 There are abundant research pipelines.
In the future, the CGT market can expect to benefit from the advantages of technology, policies, capital, etc.
The research and development related to CGT is in full swing.
There are about 1,300 cell and gene therapy projects in the world.
Regionally, the United States is the country with the largest number of CGT pipelines, with more than 600 pipelines, followed by China with more than 300 pipelines
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There are a wide range of therapeutic areas, mainly in the field of cancer, accounting for more than 60%
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From the perspective of clinical stage, 39.
5% of the global clinical are in phase I, 28% are in clinical phase I-II, 25% are in clinical phase II-III, and 6% are in clinical phase III
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From the perspective of clinical pipelines, most CGT projects are still in the early clinical stage, and with the advancement of clinical pipelines, CGT products may show a trend of accelerated listing
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Since their approval in 2017, sales of Yescarta and Kymriah have risen steadily, with sales of the two products in 2020 of $563 million and $474 million, respectively
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The compound annual growth rate from 2017 to 2020 is 332% and 329%, respectively
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The high-speed volume makes more CGT products have the potential to become blockbuster drugs in the future, and is also expected to drive the "nuggets fever" of CGT research and development
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2021 can be described as the first year of CAR-T cell therapy in China.
In June last year, Fosun Kite’s CAR-T product Akilunsai Injection (Yikaida) was approved, and WuXi Junuo’s CAR-T was approved in September.
The product is Rekilenza Injection (Benoda)
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The listing of these two drugs provides a new treatment method for patients with advanced hematological tumors in China
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iKelda is an autologous immune cell injection prepared from autologous CD19 chimeric antigen receptor T cells (CAR-T) genetically modified by a retroviral vector carrying the CD19 CAR gene.
It is the first approved drug in China.
CAR-T drugs
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After Fosun Kite introduced Yescarta from Kite (a company of Gilead Sciences, the world's first CAR-T product approved for the treatment of non-Hodgkin's lymphoma) from the United States, it carried out technology transfer and was authorized for localized production in China.
Targeted human CD19 autologous CAR-T cell therapy products
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The approval of iKelda is based on the results of a single-arm, open-label, multi-center bridging clinical trial conducted by Fosun Kite in China, which verified its efficacy and effectiveness in Chinese patients with refractory aggressive diffuse large B-cell lymphoma.
security
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Benoda is the second CAR-T product approved for marketing in China, the first approved Class 1 CAR-T product in China, and the sixth approved CAR-T product in the world
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Ruijirenxai injection is a CAR-T product independently developed by WuXi Juno on the basis of JCAR017 from Juno in the United States
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On April 3, 2022, the CDE has granted Breakthrough Therapy Designation to Benoda for the treatment of mantle cell lymphoma
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03 CGT treatment industry policy In June 2021, Fosun Kite's akirenxe injection was the first to be approved, becoming the first CAR-T product on the market in China
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Prior to this, CGT therapy was once frustrated by doubts about its safety, but from the perspective of national policy, after more than ten years of encouragement and standardized policy guidance, the field of CGT therapy in China has gone through three stages of development, and it has now entered Standardized development stage
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Let's review these three stages
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?Free development stage (1993-2015) In 2009, the Ministry of Health promulgated the "Catalogue of Class III Medical Technologies Allowed for Clinical Application", which included autologous immune cells (T cells, NK cells) therapy technology into the third class of medical technologies catalog
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In 2015, the "Administrative Measures for Stem Cell Clinical Research (Trial)" proposed the application requirements and specifications for clinical research on stem cell therapy, and stem cell therapy-related technologies are no longer managed in accordance with the third category of medical technology
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In the same year, the State Council cancelled the non-administrative licensing examination and approval for the clinical application of the third type of medical technology, streamlining administration and delegating powers, and the administrative management of medical technology was changed from the examination and approval system to the filing system, which reduced the time and energy cost caused by various cumbersome examination and approval procedures
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? Adjustment stage (2016) The "Wei Zexi Incident" in April 2016 sounded the alarm on the safety of CGT therapy.
The National Health and Family Planning Commission immediately suspended the clinical application of all unapproved third-class medical technologies All immunotherapy techniques are required to be used in clinical research only
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In 2016, the "13th Five-Year" National Science and Technology Innovation Plan proposed to develop advanced and efficient biotechnology, and carry out key technologies such as major vaccines, antibody development, immunotherapy, gene therapy, cell therapy, stem cell and regenerative medicine, and human microbiome analysis and regulation.
research
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? Standardized development stage (2016-present) In 2017, the State Food and Drug Administration promulgated the "Technical Guidelines for Research and Evaluation of Cell Therapy Products (Trial)", which proposed the safety, Valid, quality-controllable general technical requirements
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In 2019, CDE solicited opinions on the "Technical Guidelines for Pharmaceutical Research and Evaluation of Gene Therapy Products and Immune Cell Therapy Products" to provide guidance on the pharmaceutical research and production process of gene therapy and immune cell therapy products
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In 2021, the "Technical Guidelines for Clinical Trials of Immune Cell Therapy Products (Trial)" will put forward suggestions and recommendations on the technical issues of exploratory clinical trials and confirmatory clinical trials of cellular immunotherapy products, and standardize the evaluation methods of product safety and efficacy.

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04 Summary In a word, CGT therapy is another blockbuster drug after small molecules and macromolecules.
It has the advantages of long-lasting efficacy, multiple targets, and coverage of refractory diseases in a single treatment.
At the same time, CGT technology is based on gene therapy vectors.
Process development and quality control are difficult, and are closely related to basic research such as genes
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"The Fourteenth Five-Year (2021-2025) Plan for the National Economy and Development of the People's Republic of China and the Outline of the Vision for 2035" proposes to tackle key scientific and technological frontier fields, gene and biotechnology, genomics research and application, genetic cells and genetic breeding, Technological innovations such as synthetic biology and biopharmaceuticals, and research and development of vaccines, in vitro diagnostics, and antibody drugs, and CGT-related fields have good development prospects in China
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