Summary of the most full CAR-T drug market approval.

On June 6, 2020, Nanjing Legendary Bio was listed on NASDAQ, and CAR-T drug became a hot topic in the industry againAnd WHAT about the registration approval of CAR-T drugs in China? Below is the author's summary of THE CAR-T drug approval process and trendsSince Nanjing Legend received the first domestic clinical trial approval for CAR-T drug on March 13, 2018, car-T drug development projects have seen a blowout growthAs of 31 May 2020, a total of 41 IND declarations of these drugs were accepted by CDE, as shown in table 1 on indications and targetsNote: (1) During the period of approval to carry out clinical trials, applications for new indications and acceptance of new clinical trials (with new acceptance numbers) are counted according to the new declared varieties(2) Under the same acceptance number, there are several indications of the declaration, according to a declared variety countSupplemental applications submitted due to significant changes (experimental programs, pharmaceutical, non-clinical lysmic important safety findings, etc.) are counted according to the same declared variety(3) Long-term follow-up application for registration declaration of imported drugs (with new acceptance number) shall be counted according to the same declared variety(4) NDA application, according to the same IND declaration symbol count28 filing units and 6 targets in 41 accepted registration applicationsBecause many units declared a number of indications and targets, according to indications and drug targetstatistics, a total of 33After quarterly statistics by year, there are 37 (see figure 1 below)can be seen from Figure 1, whether from the number of declared varieties, or from the number of units declared, 2018 can be called CAR-T registration declaration of the most "crowded" yearEspecially in the first two quarters, 19 declared varieties, the cumulative number of declared units reached 14, accounting for almost half of the total number of declarations so farThe number of registrations now averages less than 10 (homes) per year, and the seasons are around 1-2 (homes)by KYMRIAH and YESCARTA first listed stimulus, CD19 similar CAR-T varieties of domestic declaration sharply increasedIn mid-2018, the number of processes reached a staggering 23, accounting for 56% (23/41) of total CAR-T filings to date, and 74% (23/31) of similar filings, especially in the first two quarters By 2019, the number of registrations will be reduced to 4 (homes) (see figure 2 below) it is worth noting that a small number of enterprises began to lay out other CAR-T varieties, winning the first opportunity As Nanjing Legend declared BCMA-CAR-T (the world's first new target for multiple myeloma), Kozybio declared GPC3-CAR-T (the world's first new target for solid tumors) (see table 2 below) 2018 this wave of CAR-T registration fever has made the review and approval process extremely "congested" and increased competition among companies A significant number of reporting units failed to obtain approval for clinical trials or to obtain implied permission for clinical trials (Notes) The original State Administration of Food and Drug Administration (CFDA) No 50 of 2018 adjusted the clinical trial approval process to: "From the date of acceptance and payment of the application, the applicant has not received CDE denial or challenge opinion, may carry out drug clinical trials in accordance with the submitted program", that is, the implied licensing system, implemented on July 24, 2018, a total of 19, 90,990 clinical units approved in the following table 3 Among them, Kozy bio declared targets for CD19 and BCMA (for blood tumors), GPC3 and CLDN18.2 (for solid tumors) of 4 indications, approved 3, 2 have entered The I/II period, the largest domestic Chongqing Precision Biology has also been approved for three indications The two approved indications are Nanjing Legend, Shanghai Hengrun Dasheng, Shanghai Mingju, Beijing Art Miao, Heyuan Biology and Huadao Bio There are 11 types of approved clinical indications, of which 9 are blood tumors and 2 are solid tumors With the exception of Two solid tumors (HCC and Gastric Cancer/Pancreatic Cancer) indications declared by Cozico, the remaining unit reported indications are blood tumors, including MM, B-ALL, and B-cell-derived lymphoma (including B-NHL and DLBCL) a total of 26 clinically approved varieties of registered CAR-T drugs, with an approval rate of 63.4 per cent (see table 4 below) Among them, CD19-CAR-T varieties approved the rate of about 60% This is well below the overall approval rate of CDE (the average approval rate for the last two years is 84% ) in the internal data of Thesa At present, most units of declared varieties are still in the clinical Phase I stage, and even clinical trials have not yet started The fastest-moving are Nanjing Legends, Kozi Bio, Shanghai Hengrun Dasheng and Chongqing Precision Creatures, as well as Shanghai Fosun Kate and Novartis (China) The former has a first-mover advantage, and technical strength, the latter is also carried out earlier, there is relatively mature experience can be introduced digestion , on February 26, 2020, YESCARTA (CD19-CAR-T) in the domestic counterpart - Fosun Kate's Ijilillonse injection (proposed name, code name, code-named FKC867) of the new drug listing application (NDA) has been accepted adult LBCL patients treated for recurrence or difficulty after second-line or above systemic treatment, including non-specific DLBCL, PMBCL (primary transsexual B-cell lymphoma), HGBCL (higher-order B-cell lymphoma) and TFL (DLBCL for the conversion of optometry lymphoma) This is the first CAR-T cell therapy product to be officially accepted by the State Bureau for patients with multiple myeloma who relapse to treat, Nanjing Legend recently updated its long-term follow-up data on phase I.b/II clinical treatment of BCMA-CAR-T (median of 11.5 months), showing a total efficiency of 100%, a total remission rate of 86%, and a 9-month survival rate of 86% similar, the latest follow-up results of the Cozibiological report also showthat that in patients with multiple myeloma who were treated with multiple lines of treatment, after treatment with BCMA-CAR-T, good safety and significant effectiveness were shown, with a total remission rate of close to 80%, and a median progression-free survival of 16.6 months data is very close So are they all likely to be approved by the end of the year? Perhaps, let's take a look at the approved CAR-T drugs, Novartis's KYMRIAH and Kate's (now Gilead's) YESCARTA, and their path to the market may be someinspiration (see figure 3 below) For the declaration of pre-B-ALL indications, KYMRIAH from indto situ to BLA approval, almost 3 years, even for DLBCL indications supplementary applications, also took about 1 year YesCARTA's declaration of DLBCL indications is similar to that of about three years CDE's standard approval process for NDA is 150 working days Combined with the bumpy approval process of KYMRIAH and YESCARTA, there will be a lot of uncertainty about the listing of the CAR-T varieties of Nanjing Legend and Kozi Bio before the end of the year, and there may be many challenges in the approval process By contrast, Fosun Kate and Novartis China may have done better with their previous successful approval experience 2020, it is bound to be a year of dark tide for CAR-T drugs It remains to be seen whether the Nanjing legend can create the legend again Wen, Ke Zhikang Medicine Di-Second.