The First Domestic CAR-T Went Overseas, And The FDA Approved It!

The highly anticipated results of the first domestic CAR-T to go overseas were announced.

On February 28, the Biologics License Application (BLA) of Legend Bio's CAR-T therapy cilta-cel targeting B cell maturation antigen (BCMA) was officially approved by the FDA for the treatment of relapse/ Patients with refractory multiple myeloma (r/r MM). This is the first domestic CAR-T cell therapy approved by the FDA.

cilta-cel is a directed chimeric antigen receptor T cell (CAR-T) therapy targeting B cell maturation antigen (BCMA) independently developed by Legend Bio. The therapy contains 4-1BB co-stimulatory Domain and two BCMA-targeting single-domain antibodies designed to increase their comprehensive ability to target cancer cells for the treatment of adult relapsed/refractory multiple myeloma (MM).

In December 2017, Janssen and Legend Bio entered into a licensing agreement, which granted Janssen the rights to co-develop and market cilta-cel globally. cilta-cel received the first CAR-T clinical trial application (IND) approval from the State Drug Administration in 2018, and the US FDA's IND approval in the same year, followed by FDA breakthrough therapy and orphan drug designation in 2019 Obtained the Priority Medicine Designation (PRIME) qualification of the European Medicines Agency and the breakthrough therapy designation granted by the US FDA. In August 2020, it was awarded China's first "breakthrough therapy" qualification. In December 2020, Legend Bio submitted a rolling Biologics License Application (BLA) for cilta-cel to the FDA. In April 2021, Johnson & Johnson/Legend Bio has completed the rolling submission of the BLA application for Sidakhi Orenza to the FDA, and the FDA will give the approval result in November of that year; however, in November, the approval was delayed by the US FDA and will be finalized The approval date is adjusted to February 28 this year.

The FDA approval is based on results from the pivotal Phase Ib/II CARTITUDE-1 study evaluating the efficacy and safety of cilta-cel in patients with relapsed/refractory multiple myeloma. The study results showed that at a median follow-up of 12.4 months, the independent committee-reviewed objective response rate (ORR) was 97%, including 67% sCR (strict complete response), and 92.8% of patients achieved a very good partial response ( VGPR) and above. Grade ≥3 cytokine syndrome (CRS) occurred in 4%, and grade ≥3 neurotoxicity occurred in 9%.

Up to now, a total of 7 CAR-T therapies have been approved in the world, namely Kymriah of Novartis, Yescarta of Gilead, Tecartus, Breyanzi of BMS, and Abecma, co-developed with Bluebird Bio. WuXi Junuo's Ruiki Orenza injection (trade name: Benoda) and Legend Bio's Sidaki Orenza, among which, only Abecma and Sidaki Orenza target BCMA, and the other five All are CD19 CAR-T cell products. Abecma was just approved in March last year, with a price of $419,500 and sales of $164 million in 2021. There is still a lot of market space left for Sidakhi Orenza.

At present, the disclosed sales of several CAR-T therapies in 2021 are:

Kymriah: 2021 revenue of $587 million, a year-over-year increase of 22%. At present, Kymriah-related clinical trials are also being carried out in my country. In October 2019, Kymriah obtained the default approval for clinical trials from the State Food and Drug Administration, and the indication is relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.

Yescarta: 2021 revenue of $690 million, up 23% year-over-year. At present, Yescarta (Ekililenza injection) has been approved for marketing in China in June 2021, for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after second-line or above systemic therapy, including diffuse large B-cell lymphoma B-cell lymphoma (DLBCL) unspecified, primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma and DLBCL transformed from follicular lymphoma, currently not available for newly treated lymphoma patients and other For the treatment of cancer, the domestic price is 1.2 million yuan per injection (about 68ml). It is also worth mentioning that, due to the extremely high requirements of CAR-T therapy on the treatment center and treatment team, in the previous interview with Fosun Kite by Medical Valley, relevant executives revealed that Fosun Kite is working with key cities in various provinces across the country. The Hematology Department, Lymphoma Department and Cancer Hospital of the General Hospital will jointly build an international standard CAR-T treatment center, which will initially cover 70 hospitals. These hospitals must be certified by the quality department of Fosun Kite and a third party before they can become iKiliLan Sai injection treatment center.

Tecartus: $170 million in 2021 revenue.

Breyanzi: As a product of BMS that was only approved for listing in February 2021, because Novartis and Gilead have obvious first-mover advantages in similar products, Breyanzi's first-year performance was $87 million. However, BMS still has high hopes for Breyanzi, and it is also regarded as one of the 5 drugs that will provide an important contribution to BMS sales in the next two years. It is expected to achieve more than $3 billion in revenue in 2029.

Abecma: 2021 revenue of $164 million. As the world's first BCMA CAR-T cell therapy to receive regulatory approval, Abecma was approved in the United States in March 2021, the European Union in August 2021, and recently in Japan.

Ruiki Orenza Injection: Approved by the State Food and Drug Administration in September 2021, and there is no relevant revenue data yet. According to the previous listing price in Guangdong Province, it is priced at 1.29 million yuan per vial, each with a volume of about 5mL and containing no less than 25×10^6 CAR-T cells. It is worth mentioning that recently, WuXi Junuo announced that the China National Medical Products Administration has accepted the new adaptation of Ruikiolanza injection for the treatment of patients with relapsed or refractory follicular lymphoma (r/r FL). Symptom Marketing Authorization Application (sNDA). This is the second marketing authorization application for Reiki Aurexa Injection, which is expected to be the first cell therapy product approved in China for the treatment of r/r FL patients.