Cellular immunotherapy has experienced a long history of development, and ushered in a breakthrough in recent years. Up to now, there are 366 car-t products under research in the global market, and three car-t products have been approved to go on the market, including yeskarta and tecartus of kite
Pharmaceutical and kymriah of Novartis. With Fosun Kate's car-t products nearly approved, it is expected that several car-t products will be approved and put on the market in 2021, and the commercial application of cell therapy in China will be launched this year.
But the development of an emerging technology will inevitably face many problems. How to price car-t therapy? How much room for decline in the future? How about the capacity?
1、 What are the difficulties in commercialization of car-t therapy?
Dr. Wang Yanbin of beiheng biology said that cell therapy is still in a very early stage of development, and each technology has its own development process. Since the first product of cell therapy was launched in 2017, three products have been approved, and more products will appear in the future. Moreover, car-t as a highly personalized treatment method, can not achieve mass production, high production costs, and millions of treatment costs also lead to limited access to car-t therapy.
The manufacturing and application process of cell products is complex, and the whole process needs to be carried out in a sterile, toxin free and accidental pollution-free environment. A series of processes such as cell extraction, separation, induction, amplification and reinfusion need to be completed in a relatively short time, which has high requirements for technical personnel and strict requirements for storage and transportation. Moreover, the application scenario of cellular immunotherapy must be hospitals, which also need to make adequate preparations. Biopharmaceutical companies need to cooperate with the hospital in depth to complete the collection of patient samples to the cell transfusion.
In addition, the safety of car-t therapy needs to be further improved. At present, three approved car-t therapies have shown outstanding efficacy in clinical trials, but the safety problem is also prominent. The labels of these three therapies have been given black box warnings by FDA, including cytokine release syndrome (CRS) and neurotoxicity (NT). In addition, adverse reactions include allergic reaction, severe infection, prolonged hemocytopenia, decreased immunoglobulin, secondary malignant tumor, etc.
2、 How to price car-t products? How much room for decline in the future?
In fact, the total cost of car-t includes not only the above-mentioned drug prices, but also many other medical expenses, such as lymph node dissection and car-t adverse reaction management costs, hospitalization expenses and so on. Although car-t therapy has obvious advantages in the treatment of blood diseases, millions of treatment costs can not be borne by most patients.
The pricing of car-t therapy in China is about to be announced, and there may be some price reduction. However, considering the high production cost, marketing expenses and early-stage R & D investment, the price reduction space in the future is limited. Moreover, for innovative drugs, especially cell therapy drugs such as car-t, it is not realistic to let medical insurance pay for them in the short term, and it is still unknown how many patients can bear the high cost of treatment. Another bottleneck of auto car-t products is the limited production capacity, which is usually close to the commercial production base of GMP, but the annual production capacity can only meet the needs of 1000 patients. It can be predicted that the commercialization will face many problems and challenges in the future.
At present, cell therapy is in the era of individualized therapy. With the continuous emergence of new technologies, we are still full of confidence in the cost reduction of future products. The key to reducing cost and improving accessibility is technological innovation. Dr. Wang Yanbin said that the general car-t developed by beiheng bio can significantly reduce production cost by 15 times compared with auto car-t.
3、 Future development trend of car-t products
For the future development trend of car-t therapy, Dr. Wang Yanbin mentioned the following points:
1. Development of auto car-t to universal car-t
Universal car-t therapy is essentially a kind of allogeneic car-t cell therapy, which does not need to separate T cells from patients, but uses T cells donated by healthy volunteers By gene editing technology, T cell TCR and other gene knockout can not only avoid the host's immune rejection of car-t cells, but also avoid the immune attack of allogeneic T cells on host organs (GVHD). Compared with auto car-t, universal car-t has the advantages of low price, stable quality and high success rate, so it can achieve standardized batch preparation, timely supply and low cost.
2. Breakthrough the bottleneck of poor curative effect of solid tumor
Car-t research of solid tumor is also a hot spot. At present, there are few targets of cellular immunotherapy with significant clinical effect, mainly focusing on CD19, BCMA and other blood tumor targets. GPC3, claudin18.2, NKG2D and other targets in the study of solid tumor clinical efficacy did not meet expectations. In the next few years, car-t therapy will make breakthroughs in how to overcome the microenvironment and heterogeneity of solid tumors.
3. From monotherapy to combination therapy
Car-t combined with drug therapy to enhance the efficacy and prognosis is also a development trend in the future. For example, car-t combined with immune checkpoint proteins (such as PD-1, PD-L1), oncolytic virus and Btk inhibitors can improve the efficacy, safety, survival and quality of life of car-t.
In addition, there are many other cell therapy products, not just car-t. in the future, car-nk, TIL, tcr-t and car-m may play a role in different indications.
epilogue
The emergence of car-t therapy makes more patients see the possibility that some diseases can be cured. It provides a choice for the diseases that are difficult to cure or the current treatment standard only relieves symptoms to varying degrees. For the Chinese market, the exploration of cell gene therapy from technological innovation to industrialization and commercialization has just begun. The process development, laws and policies, application experience, high cost and commercialization development of car-t technology need to be solved.
The development of an emerging technology is bound to face many problems, but with the update and iteration of the technology, cellular immunotherapy will win huge market potential after breaking through the universality problem, solving the safety problem and expanding the indications, and bring the hope of cure to patients.
What do you think of the first domestic car-t product, Agilent? Welcome to comment and discuss~
Introduction of experts:
Wang Yanbin, Ph.D., COO of behemoth. Beiheng bio is a leading innovative Biomedical Company in the development and commercialization of cell therapy products. It is jointly founded by doctors from top universities at home and abroad and operation teams with rich business experience. The fifth generation of "off the shelf" universal car-t cell therapy products developed by beiheng biology, with the international leading R & D level, is expected to fundamentally solve the current car-t "high cost, long time, difficult production, personalized" dilemma, and truly realize the accessibility of immune cell therapy. Build a bridge between life and health, let every patient get a chance to cure.
January 26, 2021
