Behind the upcoming approval of the first CAR-T: the pile CD19 market has become Red Sea

Recently, according to the Official Website of the State Drug Administration (NMPA), Fosun Kate CAR-T product Aquilonsai injection application has entered the administrative approval stage.
approved, it is also considered to be the first car-T therapy product approved in China and the fourth in the world.
"zero breakthrough" news immediately brush screen, China's CAR-T therapy or finally to the commercial "dawn eve."
And in addition to Aquilan race injection, the current domestic declaration of the listing of CAR-T products and the drug Ming Juno's Ricky Lunsai injection, the product in June last year to the national CDE to submit a listing application, is the second domestic declaration of the listing of CAR-T therapy.
It's worth noting, however, that whether it's Fosun Kate or The Drug Ming Juno, or the three CAR-T therapy products that have been approved overseas, they're all a common target: CD19.
, CD19 has become a successful and popular target in car-T cell therapy.
data show that CD19 is currently the target of CD19 car-T clinical trials accounted for up to 53% of the project, and in China 357 CAR-T clinical trials, CD19 target trials involved as high as 175.
the other side of the hot race, or a brutal and realistic competition.
as some industry insiders have admitted, "Domestic CD19 CAR-T has hundreds of similar products, clinical trials will rob patients, where do you come from the market?" "1, more than half of the CAR-T clinical trial pile CD19 target as one of the tumor-related antigens, CD19 antigens are generally expressed in normal B cells and tumor B cells, in other tissues and blood cells are not expressed, so it is considered the ideal target for CAR-T treatment of B cell tumors.
, major pharmaceutical companies and institutions have shown great enthusiasm for CD19 targets, and in the field of CAR-T treatment of hematoma, CD19 targets have become the most frequent research object.
relevant information, the current global clinical research CAR-T project involves more than 47 targets, in addition to star target CD19, but also including BCMA, CD22, CD20 and other popular targets.
, according to Clinical Trials, CD19 is currently the world's target car-T clinical trials accounted for as much as 53%, BCMA targets in second place, accounting for 14%.
same time, about 75% of CAR-T clinical trials are concentrated in hematomas, which are still small.
Global CAR-T Research Project Adaptation and Target Distribution (Source: Clinical Trials, Guotai Junan Industrial Research Institute) Clinical Trials further points out that as of June 30, 2020, there were more than 600 registered CAR-T therapeutic clinical trials worldwide, with China leading the world with 357 clinical trials and the United States second with 255.
china and the U.S. account for about 88.8% of the world's CAR-T clinical trials, and the number of clinical trials in China is already 1.4 times that of the U.S. (data may not be complete, for informational purposes only).
the number of car-T clinical trials worldwide (Source: Clinical Trials) Domestically, CD19 is the most common study subject of CAR-T therapy in the field of hematoma, with 175 trials involving this target, of which 128 are C D19 CAR-T single-drug therapy, while CD19 CAR-T cells are also used in association with other treatments, such as CART-22 (18 trials) and CAR-T-20 (13 trials).
BCMA was the second most studied target, with 43 trials, 27 of which used BCMA CAR-T as the sole treatment.
the distribution of car-T test targets for hematomas currently registered in China (Source: Clinical Trials) of course, CD19 has indeed been a great success in the field of hematomas.
well-known, novart's Kymriah, Gilead's Yescarta and Tecartus are currently on the market worldwide, all of which target CD19.
as early as August and October 2017, the FDA approved the listing of Kymriah and YesCarta, and Tecartus was approved in July 2020, three years apart.
CAR-T may not be able to call it a "success" in terms of annual sales of $278 million and $456 million in 2019 for Kymriah, YesCarta.
There is a view that a promising new drug should maintain very high growth growth in each quarter of the first few years of the market, and from the current CAR-T sales overseas, the market because of concerns that its sales are not as good as expected, the business outlook is difficult to support the overall market valuation, and look at the decline of CAR-T's industry prospects.
2, China CAR-T market: homogenization is serious, fierce competition so the domestic market? Not to mention the prospect of commercialization, in fact, in addition to the aforementioned Mention of Fosun Kate and Drug Ming Juno, the current domestic other CAR-T products in the clinical research stage are also mostly around cd19 targets, target adaptation is mainly concentrated in B-cell lymphoma, non-Hodgkin's lymphoma, leukemia three categories, fierce competition and homogenization serious.
following, we count the domestic layout CD19 CAR-T major enterprises and related products specific situation.
combing process, we found that dozens of domestic enterprises have received CD19 CAR-T clinical approval, of which Fosun Kate and Pharmaceutical Ming Juno in the first echelon, has been in the listing approval process, the second echelon including Heyuan Biological, Yi Miao Shenzhou, Koji Bio, Galaxy Biology, Hengrui Dasheng, Bosheng Gianco and so on have also entered the I./II.
following are the specific situation of the domestic CD19 CAR-T layout enterprise.
CD19 CAR-T part in the research enterprises (incomplete statistics, may be wrong, welcome to point out) (Source: corporate website, public information / cartat: shell society) 1, Fosun Kate Akilon sai injection is Fosun Kate from the United States Kite introduced YESCAR technology, and authorized to local production in China CAR-T therapy products, The adaptations approved for this listing are adult patients with relapsed or refractic large B-cell lymphoma after treatment of second-line or above systemic treatment, including diffuse large B-cell lymphoma (DLBCL) non-special-finger type, primary vertical B-cell lymphoma (PMBCL), high-level B-cell lymphoma, and filter lymphoma transformation DLBCL.
a registered clinical trial study called ZUMA-1 evaluated the efficacy and safety of Yescarta( i.e. Equililonsai injections) in 101 adult patients with relapsed/re treatable large B-cell lymphoma.
long-term follow-up results showed that follow-up ≥4 years (median, 51.1 months), Yescarta treatment brought lasting relief to patients, with a median total survival (OS) of 25.8 months and a four-year OS rate of 44%.
2, the first company in China to obtain CD19 CAR-T IND clinical approval is actually drug Ming Juno, but then Fosun Kate first submitted a listing application.
was founded by Drug Mingkangde and Juno of the United States, and the Ricky Lunsey injection was introduced to Juno JCAR017 and filed for listing on June 30, 2020.
this listing application for three-line treatment for diffuse large B-cell lymphoma (DLBCL).
According to the announcement disclosed by Drug Ming-Juno, The ryquilansai injection has been shown to be effective in registered clinical trials treated in patients with a large number of pretreated and poor prognosis r/r DLBCL, with an optimal ORR of 75.9% and an optimal CRR of 51.7% as of June 17, 2020.
3, Kozi Biocozi Bio was established in 2014 to develop innovative car-T cells and other tumor immunotherapy drugs, covering blood tumors and solid tumors, of which the clinical phase of the four CAR-T therapies targeted CD19, BCMA, GPC3 and Claudin 18.2.
CT032 humanized CD19 auto-CAR T cell injection was independently developed by Kozi Bio, with the target adaptive disorder being relapsed/difficult to treat non-Hodgkin B-cell lymphoma.
March 2019, CT032 clinical trials applied for implied CDE approval.
4, hemolytic biology CNCT19 cell injection is a CAR-T cell therapy product with independent intellectual property rights of hemolytic organisms targeting CD19, derived from the long-term technological innovation accumulation of the Hospital of Hematology (Hematology Research Institute) of the Chinese Academy of Medical Sciences, aimed at meeting the urgent clinical needs of malignant blood tumors in China.
November 2019, CNCT19 obtained implied approval for two clinical trials in China for recurring or resuscitable acute lymphoblastic leukemia, recurrence or recurring invasive B-cell non-Hodgkin's lymphoma.
, CNCT19 clinical trials for non-Hodgkin's lymphoma have entered phase 2 clinical phases, with clinical research leading the way.
5, Yimyo Shenzhou / Synthesic Pharmaceuticals in July 2020, Yi mei Shenzhou announced that the company CD19 CAR-product IM19 treatment recurrence / difficult to treat non-Hodgkin's lymphoma clinical trial through the Beijing Cancer Hospital ethics review, will soon be launched Phase I clinical trials.
in a previous clinical study of 22 patients with relapsed non-Hodgkin's lymphoma, the objective remission rate of IM19 single-drug therapy reached 73% and was safe.
In addition, Yimyo Shenzhou has reached a partnership with Synthesic Pharmaceuticals, which will be responsible for the registration and commercialization of IM19 in China and some overseas regions, and yiyi Shenzhou will receive advance payments, milestone payments and sales share.
6, Galaxy Bio/Horsepower as early as October 2018, Galaxy Biology and its subsidiary Horsepower jointly developed the CAR-T drug "anti-CD19 molecular chime antigen-modified self-contained T lymphocyte injection" obtained clinical experimental approval, adaptive to lymphoma.
results from an earlier clinical trial, the drug was effective and did not have severe cytokine storms (CRS) or neurotoxic adverse reactions.
7, HangRun Dasheng Hengrun Dasheng was founded in 2015, the company is now forming a CAR-T technology-led, TCR-T cell therapy project, CAR-NK cell therapy project, lysovirvirus therapy and other research and development projects in parallel to promote the product pipeline.
Hengrun Dasheng in the study of anti-human CD19 T cell injections are currently in China to obtain two clinical trial approvals for the adaptation of the treatment of relapsed / refractic CD19 positive lymphoma, as well as the treatment of recurring / refractic CD19 positive acute lymphoblastic leukemia.
8, Bosheng Gianco December 2019, Bosheng Gianco "target CD19 self-embedded antigen-infusion agent" new drug clinical trial application was officially approved by CDE, the adaptive 18-70 years old recurrence or refratic B cell acute lymphoblastic leukemia.
It is learned that Bosheng Gianco this approved clinical CAR-T drugs, is the first in accordance with the full closed system, fully automatic process production requirements to declare and obtain clinical trial approval of CAR-T drugs, in the early clinical verification studies, showing excellent clinical mitigation rate.
9, precision biopCAR-19B cell autolognation preparation is independently developed by Chongqing Precision Bio, for CD19 positive B cell origin of the malignant blood system developed cell immunotherapy products, in February 2019 by the State Drug Administration approved clinical trials to treat children and adults relapsed recurring refractory acute lymphoblastic leukemia (r/rALL).
it is known that pCAR-19B optimizes the CAR structure for Chinese groups, while adopting a safer gene transducting vector system for better effectiveness and safety.
10, Stansey Sdansai products include multiple pipelines covering multiple solid and hematoma areas.
December 2019, The CD19 CAR-T product ICT19G1 declared by Stansey has been approved for clinical trials to treat adult recurrence of CD19-positive B-cell line acute lymphoblastic leukemia.
it is also worth mentioning that the Sdancer pipeline in the treatment of CD19 and PD-L1 double positive NHL ICTCAR014 has also been approved by the U.S. FDA IND, officially entered clinical trials.