cilta-cel: Legendary Bio's CAR-T therapy "frontrunner"

On February 28, Eastern Time, the US FDA officially approved the legendary BCMA chimeric antigen receptor T cell (CAR-T) product Ciltacabtagene autoleucel (cilta-cel, Ciddakio Race, trade name Carvykti

In May 2021, the CILTA-CEL listing application was accepted for priority review, and the Prescription Drug User Fees Act (PDUFA) was dated November 29, 2021.

In November 2021, Legends announced that the FDA had delayed the PDUFA target action date for CILTA-CEL by 3 months to February 28
, 2022.
(The FDA extended the review time, but did not require the company to submit new clinical data, meaning that the deferred approval is not related to the CILTA-CEL trial data.
)

It is reported that the CILTA-CEL submission of the Marketing Application (BLA) is primarily based on the results of the critical Ib/II CARTITUDE-1 study, which evaluated the efficacy and safety
of CILTARE in patients with recurrent and/or refractory multiple myeloma.
Of the 97 subjects recruited, 99% received end-line therapy ineffectively, and 88% had previously received at least 3-line therapy
.

The findings showed that at a median follow-up of 12.
4 months, the ORR reviewed by the independent commissioners was 97 percent, including 67 percent of the SRRs (strict complete response), 26 percent of the VGPR (very good partial response), and 4 percent of the PR.

≥ the incidence of grade 3 cytokine syndrome (CRS) is 5%, and the incidence of ≥grade 3 neurotoxicity is 10%.

In addition to the previously highlighted clinical data, at the recent 40th J.
P.
Morgan Healthcare Annual Conference, Dr.
Huang Ying, CEO and Chief Financial Officer of Legendary Biologics, released the latest data from the CILTA-CEL clinical trial: After a median 24-month long-term follow-up, the primary endpoint overall response rate (ORR) reached 97.
9%, VGPR was 94.
9%, and 82.
5% of patients achieved sCR
.
60.
5% of patients survive after 2 years without disease progression
.
Of the 61 patients assessed by MRD, 92% achieved a negative MRD of
10-5.

In addition to this cilta-cel, which runs at the end of regulatory victory, in the field of hematology, the legendary creatures have developed single-target/double-target/three-target CAR-T products for multiple potential targets, including BCMA, CD4, CD20, CD33/CLL-1, CD19/CD20/CD22, etc
。 Among them, the autologous CD4-targeted CAR-T therapy LB1901 has passed the FDA's IND application and launched a phase I clinical trial in the United States for the treatment of adult recurrent or refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (PTCL), which is a product
with rapid development progress in the pipeline of Legend Biologics.

Notably, earlier this month, Legendary Biologics received an email from the FDA saying that Phase I clinical trials of its LB1901 had been suspended
.
As for the reason for the suspension, neither the FDA nor the legendary creatures have mentioned
.
However, it is understood that the clinical trial was not stopped by the FDA, but the patient under the test had a condition
.

In the field of solid tumors, Legend Biologics has developed a variety of products to deal with gastric cancer, liver cancer, small cell lung cancer, non-small cell lung cancer and ovarian cancer, of which LB1908 targeting Claudin18.
2 and LB1902 targeting MSLN have entered phase I clinical trials
.

In addition, Legendary Biologics also has a chimeric antigen receptor natural killer cell (CAR-NK) platform
.

The CAR-T market has great prospects, with the first targeted BCMA product to meet the competition

CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy) cell therapy has now proven to be a powerful weapon
against blood-like cancers.
The therapy is a new type of precision targeted therapy for the treatment of tumors, the principle of which is to genetically reprogram the natural anti-infective and anti-cancer immune cell T cells of the patient's blood in vitro, and this re-edited patient T cell, after in vitro culture and modification, can identify the antigen markers on the cancer cells in the
patient's body.
Subsequently, these CAR-T cells are amplified using cell culture technology and re-injected into the patient to attack the cancer
.

Up to now, the US FDA has approved 6 CAR-T cell therapies to market, including four targeting CD19 and two targeting BCMA
.

In terms of market, according to Frost & Sullivan, the global CAR-T cell therapy market grew from $0.
1 billion in 2017 to $700 million in 2019 and $1.
1 billion in 2020, and is expected to accelerate growth in the next few years, expanding to $6.
6 billion in 2024 and further growing to $21.
8 billion
in 2030.

According to the 2021 performance announcements released by major pharmaceutical companies in recent days:

The earliest to go public, Novartis' Kymriah, saw sales of $587 million in 2021, up 24%
year-on-year.

This was followed by two of Gilead's products: Yescarta had sales of $690 million in 2021, up 23% from last year; Tecartus also achieved sales revenue
of $170 million in its first full fiscal year.

Bristol-Myers Squibb's Breyanzi, which went public last year, had a poor first-year performance of $87 million, while Abecma, which was approved a month later, had first-year sales of $164 million, nearly double
Breyanzi's full-year sales.

As the world's second approved BCMA-targeting CAR-T therapy, the most direct competitor after the cilta-cel is Abecma from Bristol-Myers Squibb on the same track, and the sales of this product have some reference value for cilta-cel, although the first year sales of the product may not be satisfactory
compared to the earlier CAR-T products.

However, based on previous clinical data, the median OS of patients who had previously received class 3 therapies treated with Abecma was 24.
8 months, the ORR was 73%, and 33% of patients achieved CR.

As mentioned above, the clinical data of the legendary biological cilta-cel shows that its ORR reaches 98%, 80% of patients have achieved sCR, and the safety also has certain differentiating advantages
.

It can be seen that the sales of cilta-cel may be slightly better in the future
.

It is understood that long before the formation of cilta-cel, legendary creatures have been favored
by the giant MNC.
In December 2017, Legendary Biologics entered into a global partnership and licensing agreement
with Johnson & Johnson's Janssen.
According to the cooperation agreement, in Greater China, Legendary Bio and Janssen share the cost and share the benefits in a 7:3 ratio; In the rest of the world, the two companies are divided into
five or five.

Currently, Legendary Bio has received an advance payment of $350 million and a milestone payment
of $250 million.

Domestic enterprises are not far behind, and the competition for CAR-T targets is poised to develop

Domestically, the State Food and Drug Administration has approved the listing of two CAR-T products, both targeting CD19
.
These two products are Fosun Kate's Achillense injection and WuXi Junuo's Regie Orensai injection, it is reported that both products are cooperative products, Achillense injection is introduced by Fosun Kate to Kite, and Regie Olens injection is introduced
by WuXi Juno to Juno.

It is worth mentioning that on February 27, WuXi Juno issued an announcement that the second indication of its CAR-T product Ricky Orensai Injection has been accepted by the State Food and Drug Administration for the treatment of patients with
relapsed or refractory (r/r) follicular lymphoma (FL).

In addition, there are also domestic Heyuan Biological, Keji Pharmaceutical, Yimiao Shenzhou and other enterprises actively joined, and all of its products have entered the clinical stage
.
Its research and development targets are mainly concentrated on CD19, followed by BCMA, and there is no shortage of dual-target products
.