You can't just learn to walk and want to run.
CAR-T products have never been so entangled as they are today.
On the last working day before the Spring Festival in 2022, the Ministry of Industry and Information Technology, the National Development and Reform Commission, the Health Commission, the Medical Insurance Bureau and other nine ministries and commissions jointly issued the "Notice of the 14th Five-Year Plan for the Development of the Pharmaceutical Industry", which clearly states that in the field of biological drugs, the focus will be on the development of chimeric antigen receptor T cells (CAR-T) for new targets and new indications.
This is the second time that CAR-T has been mentioned at the national level in the five-year plan since the 13th Five-Year Plan for the pharmaceutical industry in 2016, and the importance is self-evident. It is reasonable to say that after 5 years of promotion, the market should have blossomed a hundred flowers long ago. However, to date, there are only two CAR-T products approved for listing in China.
At the same time, the National Drug Review Center promulgated the "Technical Guidelines for the Clinical Risk Management Plan for the Declaration and Listing of CAR-T Treatment Products" before the Spring Festival, which put forward a large number of requirements for the declaration of CAR-T cell therapy products, the core of which is to reduce the risk of the product. In the future, CAR-T will be strictly implemented in accordance with the new requirements.
In addition, on the payment side, the currently listed CAR-T products have not been able to pass the economic review of the National Medical Insurance Bureau.
CAR-T's policy encouragement and actual industrial development have formed a sharp contrast.
The market is not good
Businesses are trying to avoid fatalities
In 2021, Novartis' financial report showed that Kymriah's global sales of $587 million did not enter novartis' top 20 products for sale.
Kymriah is Novartis' CAR-T product, approved for marketing in the United States on August 31, 2017, for the indication of acute B-cell lymphoid leukemia in children. At that time, FDA Director Gottlieb also commented: "The approval of CAR-T products has ushered in a new era of drug treatment." ”
But three years after going public, CAR-T didn't show the good sales it had imagined. Not only in the United States, but also in China.
Fosun Kate and WuXi Junuo' self-developed CAR-T cell therapies will be listed in China in 2021, and the current market pricing of both products is not less than 1.2 million yuan. Huang Hai, CEO of Fosun Kate, has previously publicly stated that the company has cooperated with the "Huiminbao" launched by local governments and the commercial insurance of mainstream insurance companies to achieve that all patients who need treatment can be used, used well and affordably.
Doctors are not familiar with it, patients are even stranger, especially car-T, a treatment method that is different from previous drugs, makes all participants wary of sky-high drugs.
Car-T's innovation is that it uses defense mechanisms that evoke the patient's own immune system to kill cancer cells, rather than directly attacking cancer cells with foreign drugs. After the T cells are extracted from the patient's own blood, car cells are loaded and then transfused back into the patient's body to kill cancer cells.
CAR-T has obvious anti-cancer effects, but the successive death incidents of patients in clinical trials have also made the regulatory authorities feel overwhelmed.
In August 2020, a CAR-T clinical trial being conducted by biopharmaceutical company Poseida was halted due to the death of a patient. In June 2021, Tmunity, invested by Gilead and Ping An Venture Capital, died in a trial of CAR-T cell therapy for prostate cancer.
Both trials featured immune effector-associated neurotoxic syndromes or macrophage activation syndromes, which are common adverse effects in CAR-T cell therapy.
This is the thing that the authorities are most worried about. Since September 2021, the National Center for Drug Review (CDE) has issued a number of documents to ensure that the post-marketing safety risks of CAR-T cell therapy are controllable. At the end of January this year, the CDE once again issued clinical guidelines, requiring reporting companies to report the possible safety risks of CAR-T cell therapy products from the chronological order of production, transportation, treatment, drug administration, follow-up and so on.
In addition to the safety of the drug itself, CDE has also "crossed" the work of the Health Commission, requiring CAR-T reporting enterprises or marketing licensors to carry out education and training of medical staff and patients, and ensure the effectiveness of training.
In the field of CAR-T, China has woven a regulatory network composed of laws, regulations, management systems and guidelines, which is not inferior to developed countries in Europe and the United States, which is also a treatment that other drugs do not have.
For CAR-T products, the attitude of the drug approval department is actually very cautious, which will inevitably affect the use of the market.
Cost constraints Price is difficult to reduce
The narrow application surface is the reason
CAR-T, which is being used clinically in China, is actually not prescribed much at present.
In July 2021, fosun Kate's first prescription for "Yi Kaida" was issued at Tongji Hospital of Huazhong University of Science and Technology, and after 100 days of listing, at least 10 patients nationwide were ready to use "Yi Kaida". After WuXi Juno's "Benotda" was approved for marketing in September 2021, the first prescription was issued at Hunan Provincial Cancer Hospital on December 9 for diffuse large B-cell lymphoma.
Up to now, the State Food and Drug Administration has not notified the clinical adverse reactions of the two products that have been listed. However, some insiders pointed out that Fosun Kate and WuXi Juno are collecting patient use information, and the final assessment will take time.
However, the incidence of special lymphoma indications for CAR-T cell therapy is 2 in 100,000. With such a large population in China, it is conservatively estimated that only 20,000 patients are eligible for use.
Lack of a large patient population, R & D companies can not be large-scale production, resulting in the cost of products is difficult to reduce. Moreover, the efficacy of CAR-T is not as good as that of the sky.
The use of CAR-T cell therapy by medical workers in various countries is still in the clinical exploration stage. "The first problem at present is to ensure clinical efficacy." Wang Liqun, the former CEO of Fosun Kate, pointed out that if patients spend more than 1 million yuan and ultimately do not achieve the expected treatment effect, neither the patient nor the product is ideal.
The market is already impatient. According to the incomplete statistics of the Health Knowledge Bureau, the State Food and Drug Administration has received more than 26 marketing applications for CAR-T therapy, including legendary biology, Keji biology, Genxi biology, Yongtai biology and so on. After all, a user of more than one million, is everyone who wants to challenge the market.
But of the 1.2 million, how much can the company make?
CAR-T is different from other innovative drugs, the cost of CAR-T does not depend on the enterprise itself, mainly from the upstream and downstream supply chains of the industry, materials, reagents, equipment, packaging, testing, labor costs and cold chain logistics, which account for an important proportion. Wang Liqun believes that CAR-T cannot drop by 50% like PD-1, "even if the current price of millions of yuan, the profit of CAR-T cell therapy is very small." ”
This also doomed CAR-T to be unable to obtain medical insurance support.
These problems could have formed a strong social public opinion oppression with the embrace of CAR-T, just like the "700,000 sky-high drugs" in 2021, allowing the medical insurance department and enterprises to sit down and talk. Although enterprises have more concessions, good villains are progress.
In today's situation, CDE is stuck in CAR-T from the source, and I am afraid that related companies do not even have the opportunity to sit down.
Who can pay for CAR-T?
The only way out facing CAR-T cell therapy is to expand clinical indications.
In addition to B-cell lymphoma, companies are currently looking for differentiated indications. The focus of legendary organisms is multiple myeloma, Ziko biology tends to stomach cancer, hepatocellular carcinoma, and central nervous system leukemia is the breakthrough point of Yucardi Biology.
A researcher at a brokerage company told the Health Bureau that the future value of CAR-T cell therapy lies in solid tumors.
On February 4, Arcellx officially landed on the NASDAQ and raised $142.3 million to promote CAR-T therapy for the treatment of recurrent refractory multiple myeloma. In addition, there are a large number of studies focused on the treatment of neuroblastoma with CAR-T.
This may be the direction of CAR-T drug development that the country has encouraged and promoted in two consecutive five-year plans. Compared with existing targeted drugs and immune drugs, the mechanism of action of CAR-T is completely different, and it belongs to another technical path for treating tumors. Macroscopically, with CAR-T, the choice of treating tumors will be much wider.
Before the first step of the Long March, CAR-T's product attributes also need to be clarified.
In its "Reply to Recommendation No. 4371 of the Third Session of the Thirteenth National People's Congress", the National Health Commission said: "Our committee has always encouraged and supported the research, transformation and industrial development of stem cells and immune cells. The reply also made it clear that the national drug regulatory authorities have formulated supporting policies for relevant preparations to pass drug approval.
The "Guiding Principles" issued by cde this time can at least determine one point: CAR-T as a therapeutic technology involving clinicians in production, the future dominance is still in the drug regulatory department. This sets the tone for the regulatory thinking of many products of cell therapy and gene therapy.
The industry generally believes that China's supervision of cell therapy is expected to change from the "dual-track system" of health and drug supervision to the "single-track system" of regulating drugs, which is an important sign of international standardization.
Capital's sense of smell has captured changes in regulatory policy. Just this past January, 8 companies carrying out cell therapy research and development, such as Uninuo Biology and Shimai Pharmaceutical, obtained financing. The market always gives people room for imagination, which is actually a good thing for the industry.
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