In 2012, Emily, who lives in Pennsylvania, USA, participated in a clinical trial of CAR-T therapy conducted by the University of Pennsylvania. At that time, the 7-year-old girl had been fighting acute lymphoblastic leukemia for two years, and had undergone countless chemotherapy treatments to no avail. In the end, Emily became the world’s first leukemia child who was “cured” by CAR-T therapy, and what worked on her was the world’s first CAR-T therapy, Novartis’ Kymriah. Today, Emily’s tumor has not returned in 10 years, and this revolutionary therapy has also ushered in a new era of personalized cancer treatment.
CAR-T therapy, Chimeric Antigen Receptor T cell immunotherapy, can accurately identify and quickly destroy cancer cells, known as “directed cruise bio-missiles”. Since the commercialization of the world’s first CAR-T for more than 5 years, the efficacy and commercial value of this new tumor immunotherapy method have been fully verified in market practice.
The billion-dollar sales champion was born
So far, a total of 8 CAR-T products have been approved for marketing in the world, of which 6 target CD19 and 2 target BCMA, and the indications are all kinds of hematological malignancies.
In addition to WuXi Juno’s Ruiji Orunsa injection and Fuxing Kite’s Akilunsa injection, the sales of the other 6 CAR-T products have been disclosed by pharmaceutical companies such as Novartis, Gilead, BMS, and Legend Biotech. . Among these 6 products, the one with the shortest time on the market is Carvykti of Legend Bio, and the one with the longest time on the market is Novartis’ Kymriah.
Dynamic point technology organizes from public data
Novartis’ Kymriah is the world’s first FDA-approved CAR-T cell therapy, and it has been approved for three indications. In 2022, Kymriah will achieve sales of US$536 million, a year-on-year decline of 9%.as 8 modelsCAR-T therapyThe earliest and most expensive one on the market,Kymriah has become the only CAR-T product with declining revenue.Novartis stated that this is due to the fierce competition for the first-line treatment of relapsed/refractory diffuse large B-cell lymphoma. up to now,Three overseas CAR-T therapies for patients with diffuse large B-cell lymphomaAmong them, the first CAR-T product with annual sales exceeding US$1 billion has appeared, which is Gilead’sYescarta,Its sales in 2022 will reach US$1.16 billion, a year-on-year increase of 66.9%. In competition with Yescarta, the demand for Kymriah in the European and American markets has declined. Gilead’s other CAR-T therapy, Tecartus, achieved revenue of US$299 million last year, a year-on-year increase of 70%, and the growth momentum is good.
BMS’s Abecma and Breyanzi have a combined revenue of $570 million in 2022, with both products approved in the first half of 2021. Abecma is the first FDA-approved CAR-T therapy targeting BCMA for the treatment of relapsed/refractory multiple myeloma. Sales in 2022 will increase by 136% year-on-year. Breyanzi is the fourth CD19 CAR-T product approved by the FDA for third-line treatment of LBCL.According to industry analysis, based on the late entry of Breyanzi into the market and the high competition for the same target and indication, it is difficult to increase its subsequent sales.
Legend Bio’s Carvykti is the second BCMA-targeted CAR-T therapy approved by the FDA for the treatment of relapsed or refractory multiple myeloma.asThe first domestically produced CAR-T therapy that has successfully launched overseas, the price of Carvykti has been benchmarked against Novartis’s Kymriah. In the first year of listing, Carvykti earned US$134 million in revenue, which is still a certain gap compared with the US$164 million in the first year of listing of the same target Abecma.
Explore new ideas for cost control
2021 is the first year of cellular immunotherapy in China. Fosun Kite’s Akilunsa injection and WuXi Junuo’s Ruiji Orensai injection have been approved for marketing in China, setting off a wave of CAR-T in the field of cancer treatment.
According to The Lancet, as of November 15, 2021, 714 clinical studies of CAR-T cell therapy have been registered in China.The Insight database shows that as of February 23, 2023, there have been 43CAR-T Cell TherapyEnter domesticallyClinical Trials.
In January of this year, Legend Biotech’s marketing authorization application for Carvykti has been included in the priority review and approval process, and will compete with Reindeer Biotech’s Ikilunsa and Science and Technology Pharmaceuticals’ Zewoki Orunsa for the third domestic CAR-T therapy . In addition, this high-value and highly popular cutting-edge therapy has also attracted the layout of many biopharmaceutical companies such as Bangyao Bio, Saibiman Bio, Boshengji Medicine, and Hengrun Dasheng.
According to data, as of June 2022, since the first domestic CAR-T therapy, Akilunsa injection, has been on the market for one year, more than 200 patients have been treated, and the cumulative sales have reached 240 million yuan. In cooperation with more than 80 hospitals across the country, a cell therapy center has been established. At the same time, this product has been included in Huimin Insurance in more than 30 provinces and cities, and more than 50 commercial insurance institutions have included it in the reimbursement list.
It is not difficult to see that compared with several foreign products, the revenue of CAR-T therapy in the domestic market is relatively lagging behind. Behind this, product pricing is an important constraint.
At present, the prices of the two CAR-T therapies that have been approved in China are 1.2 million yuan per injection and 1.29 million yuan per injection, while the price of the lowest approved product abroad is 373,000 US dollars (about 2.57 million yuan). )/needle, more than twice that of domestic products.This means that domestic products need to obtain more than twice the sales of foreign products to achieve the same sales. On the other hand, although the price is already far lower than that of foreign products, injections with a single cost of one million yuan are already veritable sky-high prices in China, which also affects the promotion of CAR-T in the domestic market.
The two CAR-T products of Fosun Kate and WuXi Junuo have entered the preliminary review list of medical insurance negotiations, which once aroused expectations and attention, but in the end, neither of them was officially included in the medical insurance. For pharmaceutical companies, high research and development costs, high-demand raw materials, specificity of private customization, and complicated preparation processes are all reasons for their reluctance to lower prices. At the same time, the verified and temporarily irreplaceable efficacy of CAR-T products also gives manufacturers the confidence to maintain high prices.
In addition to medical insurance, the exploration of other innovative payments has achieved little success. As mentioned above, Huimin Insurance will launch curative effect insurance for CAR-T in 2021, and some commercial insurance companies will also launch special drug insurance for CAR-T therapy, with an insured amount ranging from 1 million to 3 million yuan. However, if ordinary patients need medication, there is still a large funding gap. For this reason, the international community is also trying models such as installment payment based on efficacy.
summary
At present, CAR-T therapy has made significant breakthroughs in the treatment of hematological tumors. However, as shown above, the research and development pipelines of pharmaceutical companies that have been approved for marketing and clinical use have been highly concentrated on lymphoma, leukemia, and multiple myeloma, and their targets are also limited to BCMA and CD19. When CAR-T therapy for hematological tumors has fallen into involution, the application of CAR-T in the treatment of solid tumors is still due to bottlenecks such as weak tumor tropism, strong tumor heterogeneity, immunosuppressive microenvironment, and on-target desulfurization toxicity. in the early stages.
Compared with solid tumors, the incidence of hematological malignancies is less, which fundamentally limits the market for CAR-T therapy. However, in further research experiments, CAR-T therapy has expanded its indications beyond hematological tumors, that is, autoimmune diseases with a relatively higher incidence, mainly including systemic lupus erythematosus and anti-synthetase antibody syndrome.
In addition, choosing to seek overseas commercialization and improving the awareness of doctors and patients through market education will also help to improve the ultimate market space of CAR-T therapy.
