The Paper's reporter Li Xiaoxiao
2021 is the first year of commercialization of CAR-T therapy in China.
Different from chemotherapy, radiotherapy and immunotherapy of traditional tumor treatment, CAR-T therapy belongs to cell therapy, mainly through genetic engineering technology, artificially modifying T lymphocytes of tumor patients, generating tumor-specific CAR-T cells after a large number of cultures in vitro, and then feeding them back into the patient's body to attack cancer cells, and then achieving the goal of treating diseases, which can be called opening up a new world of tumor treatment.
At the regulatory level, two CAR-Ts have been approved in China. In June, Fosun Kate's Agilense Injection (trade name: Yikaida) was approved, becoming the first CAR-T cell therapy product approved for marketing in China. In September, WuXi Junuo's Ricky Olonsai Injection (trade name: Benoda) was officially approved.
At the public level, the post of "1.2 million yuan for a shot, 2 months of cancer cells cleared" made car-T therapy successfully out of the circle. At an event at the end of September, Xu Pengpeng, deputy chief physician of the Department of Hematology of Shanghai Ruijin Hospital, who participated in the treatment process of the patients in the post, revealed: "The phone calls of hospital leaders have been broken, and the switchboard of the hospital has received hundreds of consultation calls in one night."
In addition to Fosun Kate and WuXi Junuo, there are not many entrants in the field of DOMESTIC CAR-T therapy. A research report by Yuekai Securities pointed out that in 2020, there are 335 ongoing CAR-T clinical trials in China, and the top clinical progress includes legendary biological, Keji Pharmaceutical and other enterprises.
When car-T, a tumor treatment method, begins to make continuous progress or commercialization, how to correctly understand CAR-T therapy, and whether the million-level high price will fall, how to further reduce the price, has become an important issue facing the entire industry and doctors and patients.
IS CAR-T therapy a miracle drug? Currently, it mainly targets blood tumors
The "one shot to clear cancer cells" post once made people think that CAR-T therapy is a miracle drug, in fact, its approved indications are still limited.
From the public research results, it is currently mainly aimed at blood tumors. The CAR-T beneficiary often mentioned in the industry is emily, an American girl, who has achieved 10 years of tumor-free survival after CAR-T treatment, and suffers from leukemia in blood tumors. At present, the indications for the approval of the two DOMESTIC CAR-T products are lymphoma.
Did the patient in the above fire post really achieve a "one-shot cure"? Xu Pengpeng stressed that the patient's imaging efficacy evaluation results are "total remission", the body temporarily has no tumor performance, but it is necessary to further look at the long-term follow-up, the patient will return to the hospital again after 3 months after treatment to carry out efficacy assessment, if no tumor signs have been found, then from a high probability, the possibility of achieving cure in the future is very large.
Compared with hematological tumors, CAR-T therapy has limited progress in the treatment of solid tumors such as lung, liver, and stomach cancer.
"If the blood tumor is likened to a scattered soldier, the solid tumor is a stubborn enemy in the bunker, the former can be broken individually, and the latter needs to fight a tough battle." For solid tumors, CAR-T cells not only need to break through the walls of solid tumors, but also need to fight in the harsh solid tumor microenvironment after entering the solid tumor tissue, and the difficulty can be imagined. In an interview with the surging news reporter, Keji Pharmaceutical said that there is a big difference in technical difficulty in the use of CAR-T therapy for hematological tumors and solid tumors.
Legendary Biology further explained to the surging news reporter that the target expression of solid tumors not only lacks specificity, but also has high heterogeneity, disorders of the vascular system within the tumor, dense matrix, and difficult for T cells to reach infiltration. In addition, the tumor microenvironment is mostly composed of immunosuppressive molecules and inhibitory immune cells, and even if T cells enter, their proliferation and tumor killing ability will be significantly affected.
However, from the currently announced product line, breaking through the physical tumor is the direction that all companies in the CAR-T track are working towards. In the interview, a number of CAR-T companies believe that in the future, solid tumors, including solid tumors with high incidence in China, are expected to become the main therapeutic areas of cellular immunotherapy products represented by CAR-T.
A needle of 1.2 million, why is CAR-T expensive?
In addition to words like "one shot to remove cancer cells", the figure of 1.2 million is another important reason for the attention of car-T therapy.
In fact, as early as the beginning of June this year, Fosun Kate's Agilense injection was just approved, and a sales order was circulated in the industry, according to which the retail price of Agironsey injection was 1.2 million yuan / about 68ml, which was accused of "sky-high price".
The reason why CAR-T products are so expensive is inseparable from their customized production. Fosun Kate said in a reply to the surging news reporter that because car-T cell therapy products are a highly customized drug, its price is determined by many factors, including operation, production, research and development, logistics and other costs.
"The product is currently priced at the lowest price in the world in China." In its response, Fosun Kate stressed that the current pricing of the therapy in various countries around the world is basically about 2.5 million yuan, and the original research product Yescarta (the world's second approved CAR-T product) that is fully imported from the domestic approved product is completely technology, and the process technology follows the same process in other countries.
For the pricing of CAR-T, a domestic oncologist told the surging news reporter that in foreign countries, the cost of the CAR-T drug itself is relatively expensive compared with the medical fee, and even feel that it is not expensive, while in China, the diagnosis and treatment fee is relatively cheap, and the product cost is also very expensive.
"The cost problem should ultimately be determined according to the specific conditions such as the production cost of the enterprise, and it should also be linked to the overall economic level." Doctors and patients certainly want the cheaper the better, but if innovation doesn't pay off, companies don't have the incentive to develop, and patients end up suffering. The aforementioned oncologist stressed.
How can technical means reduce the cost of CAR-T?
The preparation of CAR-T usually includes multiple complex links such as plasmids, viral vectors and CAR-T cells, and there are differences in the production methods and strategies of different enterprises, but further controlling the cost of CAR-T from technical means to achieve the price reduction target is the direction that various companies are exploring.
"International counterparts outsource the production of viral vectors, and this cost can be very high, because third-party service companies may have low yields per batch, resulting in high vector costs that are evenly distributed to each patient." Keji Pharmaceutical introduced to the surging news reporter that its plasmids, viral vectors and CAR-T are all produced independently, and there are advantages in preparation costs.
In terms of reducing production costs, WuXi Junuo has established a Next-generation (Nex-G) development strategy that includes reducing production costs from the near, medium to long term, simplifying and/or replacing/merging unit operations by improving the efficiency of raw material use, domestic substitution and implementing new technologies to achieve large-scale cost reductions.
The current CAR-T products mainly take the autologous CAR-T technology, that is, the T cells collected from the patients themselves and then processed, and the corresponding universal CAR-T - T cell source comes from a healthy donor, which can be used for multiple patients after treatment and preservation, and this technology is also an important means to reduce the cost of CAR-T.
Legendary biology mentioned: "Compared with autologous CAR-T cells, the T cells in the allogeneic universal CAR-T cells are donated by healthy volunteers and can be prepared in advance to ensure the timeliness of treatment and achieve large-scale mass production, which will reduce the cost a lot." ”
"Nowadays, researchers from all over the world are working hard to carry out innovative research and development of general-purpose CAR-T platforms and products, of course, it is still in a relatively early stage, but we believe that this technical bottleneck will be broken sooner or later." Legendary creatures are emphasized.
At a CAR-T therapy seminar at the end of July this year, an analyst who has long been concerned about the pharmaceutical industry publicly said: "We must believe that the manufacturing capacity of Chinese companies will be able to reduce process improvement and production costs starting from raw materials to the lowest in the world, and it must be able to reduce to the lowest in the world." Another analyst pointed out that from the perspective of production costs, it is estimated that domestic CAR-T products have the opportunity to drop to about 180,000, and even to less than 100,000 in the future.
Can Commercial Insurance Solve THE HIGH CAR-T Price?
If the exploration from blood tumors to solid tumors and how to reduce production costs is a scientific problem of CAR-T therapy, then how to make eligible patients afford CAR-T now or in the future is a social problem.
In July this year, the official website of the National Medical Insurance Bureau released the "Announcement on Announcing the Adjustment of the National Medical Insurance Drug Catalogue in 2021 through Preliminary Review of Drugs and Information", which includes Fosun Kate's CAR-T products. It is not yet possible to confirm whether the product can be negotiated by Medicare to reduce the price.
There is a view in the industry that under the medical insurance policy of wide coverage and basic insurance, the national medical insurance is unlikely to pay for CAR-T therapy in a short period of time. Solving the accessibility of CAR-T therapy through commercial insurance has become the common idea of all CAR-T companies.
In July this year, Fosun Kate included Yi kaida in fosun united health insurance's list of purchased special drugs, and the corresponding medical insurance product is Beyond Insurance 2020, which supports full reimbursement. In August this year, WuXi Junuo signed a strategic cooperation agreement with Magnesium Health, according to which the two sides will strengthen cooperation in the field of urban supplementary medical insurance and health insurance to reduce the payment pressure of patients through commercial insurance. In addition, Ping An e-Life Insurance 2022 also includes two CAR-T products that have been approved so far.
There are different views in the industry on whether commercial insurance can solve the problem of high prices of CAR-T therapy.
"Relying on commercial insurance to solve the payment problem of CAR-T therapy, optimistically speaking, three or four years, pessimistically, it will take five, six, seven or eight years." Xuan Jianwei, director of the Institute of Pharmaceutical Economics of Sun Yat-sen University, said in an interview with the surging news reporter that commercial insurance is not very mature in China, and at this stage, the use of some innovative payment methods and social funds may be a more feasible method.
Xuan Jianwei mentioned that there are many ideas for innovative payment methods, one of which is to pay according to the efficacy, such as "spend 1.2 million to buy this drug, the cancer is cured, and charge 1.2 million; if the drug does not work, is it possible to return a part of the patient's cost while retaining the cost of the enterprise".
A similar approach was proposed as early as August 2017, when Novartis' CAR-T product, Kymriah, was first approved in the United States, becoming the world's first CAR-T product with an initial pricing of $475,000. For the price, Novartis has publicly stated that it is discussing a "pay-for-effect" pricing scheme with the U.S. Centers for Medicare and Medicaid Services (CMS).
It is worth mentioning that CAR-T therapy also has a scale effect, and its price will decrease accordingly as the amount of use increases. Xuan Jianwei told the surging news reporter that the price of any drug can be reduced with the increase of the amount, and the same is true for CAR-T therapy, but due to special features such as CAR-T customization, "it will not drop as much as other drugs, which is a more objective assessment." ”
Editor-in-Charge: It's Winter
Proofreader: Ding Xiao