Legendary biological new products approved, drug Mingjunuo products new indications approved: "sky-high price" CAR-T therapy when can really go to the public?

21st Century Business Herald reporter Ji Yuanyuan Trainee reporter Yan Shuo reporting from Shanghai and Beijing

On August 27, Legendary Bio announced that the company's self-developed cell therapy product, Kawei Di®(Generic name: Cedarkeorensae Injection) has been approved by the National Medical Products Administration (NMPA) for the treatment of relapsed or refractory multiple myeloma in adult patients who have progressed after receiving at least three-line treatment (at least One proteasome inhibitor and immunomodulator).

According to public information, Cedarkeorentham Injection is a genetically modified autologous chimeric antigen receptor T cell (CAR-T) therapeutic product targeting B cell maturation antigen (BCMA), which is administered as a single intravenous infusion. It is worth mentioning that Cedarkeorensel Injection became the first variety to be included in the breakthrough therapeutic drug program by the Center for Drug Evaluation (CDE) of the State Food and Drug Administration in August 2020.

On the same day, Pharmaceuticals announced that NMPA had approved its CAR-T cells targeting CD19.ImmunotherapyProducts of BINODA®(Generic name: Rekeorenthal Injection) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (r/r MCL) who have undergone second-line and above systemic therapy, including Bruton's tyrosine kinase inhibitor (BTKi).

This is the third marketing approval application submitted by Mingjunuo for regiolenzai injection and the first cell therapy product approved in China for the treatment of r/r MCL patients. Rekeolensai Injection was awarded by NMPA as a breakthrough therapeutic drug for the treatment of r/r MCL in March 2022 and was qualified for priority review in December 2023.

Up to now, there are six CAR-T products in China. In addition to the newly listed Cidaciolensa injection and the approved new indications, there are also four products of Fosun Kate's Akirensa injection, Reindeer Biology's Ikeolensa injection, Heyuan Biology's Nachiolensa injection and Keji Pharmaceutical's Zewociolensa injection.

A brokerage analyst told the 21st Century Business Herald that since the listing of the world's first CAR-T in 2017, the CAR-T production process at home and abroad has been very mature. After several years of development, domestic CAR-T products have also been approved one after another. Globally, CAR-T targets are still relatively fixed and limited, and further technological breakthroughs are needed. From the statistical point of view, there is no significant difference in the clinical efficacy of the approved products, so it tests the cost control ability of each company.

At present, most CAR-T therapies require individualized preparation, and CAR-T individualized customization characteristics determine higher production costs and production management costs. The characteristic of "one shot" is also one of the reasons for the high pricing of all approved CAR-T. How to promote the accessibility of drugs has become the focus of attention.

　　New developments in two CAR-T products

The approval of Cedaryl Aurisor Injection is based on the CARTIFAN-1 of a multicenter confirmatory Phase II clinical study (NCT03758417) conducted in China to evaluate the use of Cedaryl Aurisor Injection in patients with relapsed or refractory multiple myeloma who have received at least three previous lines of treatment (including at least one proteasome inhibitor and at least one immunomodulator).

According to Academician Chen Saijuan, the main researcher of the CARTIFAN-1 clinical trial, multiple myeloma (MM) is an incurable malignant plasma cell tumor, accounting for about 10% of hematological malignancies. Patients will eventually face recurrence, and with the increase in the number of recurrences, the difficulty of treatment also increases, the quality of remission of patients is worse, and the progression-free survival (PFS) and survival time after recurrence are shorter.

Cedaroxolenex injection consists of two nanobodies targeting BCMA in tandem, which bind to BCMA-expressing myeloma cells in vivo, induce the activation and proliferation of T cells, and eliminate myeloma cells.

It is worth mentioning that the Cedarkeorensa injection is composed of legendary biological andJohnson & JohnsonIts subsidiary Janssen Company (nowJohnson & JohnsonInnovative Pharma) signed an agreement in 2017 to co-develop and commercialize. Legendary Bio is responsible for market development and commercialization in Greater China, while the rest of the world outside of Greater China is ledJohnson & JohnsonDominant. Prior to this, Cedar keorensai injection has been approved in the United States, the European Union, Japan. According to the financial report, in the first half of this year, sales of the product were $0.343 billion billion, an increase of 81.5 percent over the same period last year.

The approval of regexiolenzel injection is based on the results of a single-arm, multi-center, pivotal clinical study of its use in the treatment of adult patients with r/r MCL in China. This phase 2, single-arm, open-label study in China included patients with r/r MCL who had been treated with targeted CD20 antibodies, anthracyclines or bendamustine, and BTKi.

MCL is a B- cell non-Hodgkin lymphoma with high heterogeneity and no cure currently available. MCL patients are mainly elderly male patients, and the diagnosis is in the late stage, and the prognosis is poor. Although in recent years, the treatment plan has been developed, from traditional chemotherapy to new targeted drugs such as BTKi, which has improved the prognosis of some patients with r/r MCL, but the vast majority of patients will still progress or relapse, and the overall survival (OS) of patients with treatment failure is short (6-10 months).

Studies have shown that nearly 70% of patients with relapsed or refractory mantle cell lymphoma have achieved complete remission after treatment with Rikeolensel injection. Safety data show that the treatment is generally well tolerated, and Rikeolensel injection has become China's first commercial CAR-T product for the treatment of relapsed or refractory mantle cell lymphoma.

The above-mentioned brokerage analysts said that more and more clinical data show that CAR-T has a significant effect on the treatment of hematological tumors. At present, patients who choose CAR-T mainly meet three conditions: first, their own diseases are suitable for CAR-T therapy; second, they have received traditional treatment methods are ineffective; in addition, economic ability can support them.

It should be pointed out that "economic ability can support" can be regarded as the key to the choice of CAR-T therapy to a certain extent. Although the latest listing of Cedar keorensai injection did not give a price, but from similar products or can predict the approximate range of its price. The price of the new indication approved for the new indication is 1.29 million yuan/needle, while the other four similar products are also around one million yuan per needle.

　　How to improve drug accessibility?

On August 27, the National Health Insurance Bureau officially announced the 2024 National Basic Medical Care.InsuranceInjuryInsuranceand fertilityInsuranceThe list of declared drugs for which the adjustment of the drug catalogue has passed the formal examination, and after the relevant drugs have been reviewed and the results revised according to the procedures, the four CAR-T products have passed the preliminary examination.

Jin Chunlin, director of the Shanghai Health and Health Development Research Center, said in an interview with a reporter from 21st Century Business Herald that before this, the executive meeting of the State Council reviewed and approved the ''Full Chain Supportinnovative medicineDevelopment Implementation Program, supporting the promotioninnovative medicineThe development of the whole chain is a clear positive signal, which is actually reflected in the results of this preliminary review. In terms of price, it is worth looking forward to whether this year will break the unwritten rule of "no 500000, no 300000" according to the degree of drug innovation.

In fact, relevant companies are also exploring multiple payment methods. Take Fosun Kate as an example. According to its semi-annual report, Akilensai Injection, as the first CAR-T cell therapy product approved for listing in China, has been approved for 2 The indications have been included in more than 110 urban Huimin insurances and more than 80 commercial insurances. In January this year, Fosun Kate also launched the first lymphoma by curative effect value payment plan.

"With the development of technology, the cost and price of all new drugs will gradually decrease from the beginning of their birth to their popularity, such as vaccines and antibody drugs that have undergone a process of change from expensive to civilian in price. CAR-T therapies will be the same trend, and we are very hopeful that we will see the popularity of CAR-T drugs in the coming decades." The above-mentioned brokerage analysts said that it should be noted that safety, effectiveness, and accessibility are all of great significance to the promotion of therapy. The pursuit of accessibility on the basis of ensuring safety and effectiveness should be the common pursuit of practitioners, rather than blindly pursuing "floor price".

The brokerage analyst further stated that corporate-level cost reduction and efficiency gains are critical to driving accessibility, which includes the choice of processes, production instruments and consumables. In the future, with the expansion of market demand, if production is still in manual operation, on the one hand, the technical proficiency is very high, which is a challenge to production capacity, on the other hand, it is not conducive to reducing production costs. Therefore, the use of automated closed production systems has become a trend in the industry.

According to Fortune Business Insights data, the global CAR-T cell therapy market will be $4.38 billion in 2023 and is expected to grow from $6.37 billion in 2024 to $16.35 billion in 2032, with a compound annual growth rate of 12.5 per cent over the forecast period.

　　Southwest SecuritiesIt was pointed out that as of the first quarter of 2023, there were a total of 1332 CAR-T research projects worldwide. There are 435 cases in the preclinical stage, 8 cases are reporting clinical. 877 cases are in clinical stage, of which 604 cases are in phase I clinical, 213 cases are in phase I/II clinical, 55 cases are in phase II clinical, 4 cases are in phase II/III clinical, 1 case is in phase III clinical.

In the face of the huge market size and increasingly fierce market competition, what are the advantages of China's CAR-T layout enterprises?

"First of all, my country's population base is large, and with economic growth, the demand and investment in medical and health are increasing. Whether it is for preclinical trials or commercial production, it can provide a broader patient sample and market space; secondly, our government supportsinnovative medicineDevelopment, such as the increasingly perfect examination and approval system, as well as financial and policy support for innovative pharmaceutical enterprises, provide good opportunities for the development of domestic CAR-T enterprises. In addition, at present, some countries in the world have included CAR-T in medical insurance. With the upgrading of China's medical payment system, the accessibility of domestic CAR-T products will be further improved." The brokerage analysts said.