The legendary creature CAR-T sells well in Europe and the United States! Domestic CAR-T is still involutional! "Going to sea" through the winter?

GenScript Biotechnology recently announced that Legend Biologics' cell therapy CARVYKTI (Cedakiolence) achieved net sales of 55 million US dollars in the third quarter of this year, doubling from 24 million in the second quarter, and the total sales of the two quarters were about 570 million yuan, exceeding market expectations
.
Cedarquiolensis once again demonstrates strong market potential
.

Cedakiolensel was approved by the US Food and Drug Administration (FDA) on February 28 this year, becoming the first cell therapy independently developed in China and approved overseas for the treatment of adult patients
with relapsed or refractory multiple myeloma who have received 4 or more previous therapies.
Since then, it has obtained conditional marketing authorization from the European Commission (EC) on May 26, and was approved by the Ministry of Health, Labor and Welfare on September 27, and is about to apply for listing
in Japan.

The successful approval and commercialization of the legendary biologics cedarquiolensis in the United States has opened the precedent for domestic innovative biopharmaceuticals to go overseas in Europe and the United States, and also highlighted the clinical value and market value
of differentiated innovative products.

"At present, domestic cell therapy is gradually showing an involution dilemma!" Industry experts pointed out that the domestic CAR-T therapy research and development targets are too concentrated and the commercialization cycle is long; At the same time, although CAR-T therapy has made gratifying progress in the treatment of hematological malignancies, it still faces many challenges
in the treatment of solid tumors.

Differentiation and innovation and overseas listing have become a new way
out for pharmaceutical companies on the CAR-T track.
The legendary bio Cedarquiolensis has been listed and sold well overseas, which not only provides domestic pharmaceutical companies with ideas for products to go abroad, but also encourages domestic pharmaceutical companies to participate in global competition
in the CAR-T field.

There is a way out for global commercialization

How can innovative products "go to sea"?

As an emerging therapy, CAR-T therapy has developed hotly in the past few years, concentrated on the market, and has become the focus
of capital attention.

September 2017 Targeting CD19 

The world's first CAR-T therapy, Kymirah, was approved for the treatment of patients
under 25 years of age with relapsed or refractory B-cell acute lymphoblastic leukemia.

October 2017 Targeting CD19 

The FDA approved Gilead's Yescarta for the treatment of
adult patients with relapsed or refractory large B-cell lymphoma (LBCL) who have previously received second- or multi-line systemic therapy.

March 2021 Targeting BCMA 

Abecma, jointly developed by BMS and Bluebird Biologics, is approved by the FDA for the treatment of adult patients
with relapsed/refractory multiple myeloma (R/R MM).

June 2021 Targeting CD19

China's first cell therapy product, Fosun Kate's CAR-T product aquilencepta, has been approved by the State Food and Drug Administration for the treatment of relapsed and refractory large B-cell lymphoma
in adults.

September 2021 Targeting CD19

JW Therapeutics is approved by the NMPA for the treatment of relapsed or refractory large B-cell lymphoma (r/r LBCL)
in adults following second-line or more systemic therapy.

At present, it has been approved for marketing CAR-T therapy, mostly CD19 targets
.
Looking back at the development of cell therapy in the field of hematological tumor treatment, although cedarquiolensis is not the world's first BCMA CAR-T therapy approved for marketing, from the perspective of clinical benefits, cedarciolensis is also worth looking forward to
.

In the pivotal CARTITUDE-1 study, the overall response rate ORR/complete response rate(s)CR of 98%/78% for the primary endpoint of cedarquiolensis compared with 72%/39% for Abecma, with cedarquiolensis having a clear advantage
.
In addition, median progression-free survival for mPFS is more than 2 years, which is higher than the average of 8 to 12 months
for comparable therapies.

In the context of the complex international political and economic environment, Legend Biologics can also achieve the approval of its self-developed products in the US FDA, in the final analysis, its products are the best in class, and the safety, efficacy and other data have significant advantages
over the marketed products.

According to the clinical development plan announced by Legend Biologics on the R&D day last October, clinical trials
for more front-line treatments will be carried out in the future.

Cilta-cel Multiple Myeloma Development Program

In December 2017, Legend Biologics entered into an exclusive global licensing and collaboration agreement with Johnson & Johnson to jointly develop and commercialize cedarquiolence.

The deal alone was an upfront payment of $350 million, one of the highest
domestic license-out authorizations at the time.
Under the agreement, Legend Bio and Johnson & Johnson have a 50/50
cost and profit split in the global market.
Since then, the two companies have worked together to advance the development of
cedarquiolence.

According to the 50% sharing clause with Johnson & Johnson, Cedarqui Olencel achieved revenue of nearly 300 million yuan in the first two quarters after its overseas listing
.

In the U.
S.
, Novartis' Kymriah, Gilead's Yescarta, and Legendary Biologics' Carvykti are priced at $475,000, $373,000, and $465,000, respectively, with sales of $587 million and $695 million
, respectively, in 2021.

In contrast, in China, Fosun Kite's Yikaida and JW Therapeutics' Carteyeta, which were listed in 2021, were priced at RMB1.
2 million per needle and RMB1.
29 million/needle respectively, achieving sales of about RMB100 million and RMB30.
797 million respectively
that year.
In the first half of 2022, JW Therapeutics issued 77 Carteta prescriptions, achieving sales revenue of about 66 million yuan
.
In contrast, the overseas market sales of CAR-T products far exceed those in China
.

The R&D side is limited on the payment side

Domestic CAR-T commercialization is difficult

As the darling of anti-cancer therapy in recent years, the effectiveness of CAR-T therapy has been verified one after another, from clinical research and development to commercialization
.
According to Sullivan's analysis, it is predicted that the global CAR-T therapy market size will reach $21.
8 billion
by 2030.

The market potential is huge, and many domestic cell therapy companies have also followed suit and actively deployed the CAR-T market
.
At present, two CAR-T therapies
targeting CD19 have been approved in China, Fosun Kite and JW Therapeutics.

In addition, according to industry statistics, there are more than ten clinical trials of CAR-T cell therapy products targeting CD19 in progress
.

In addition to the popular CD19 targets, the competition of CAR-T cell therapy products targeting BCMA should not be
underestimated.

On October 18, CARsgen announced that its new drug application (NDA) for its fully human anti-autologous CAR-T product Zevoki Olencel has been accepted by CDE for adult patients
with relapsed or refractory multiple myeloma (R/R MM) who have previously failed treatment with at least one immunomodulator and proteasome inhibitor.
This is also the second BCMA CAR-T product
to be declared for marketing in China after Innovent Biologics/Reindeer Medical's Iquilenca injection in June this year.

At present, there are 2 CAR-T cell therapy products targeting BCMA on the market
worldwide.
In China, in addition to the above 2 BCMA-targeting CAR-T cell therapy products have been submitted to NDA, there are also 4 BCMA-targeting CAR-T clinical trial projects registered on the CDE drug clinical trial registration and information disclosure platform
.

According to statistics from the New Media Center of Pharmaceutical Economic News, the NMPA has received more than 27 marketing applications for CAR-T therapies, including Fosun Kite, JW Therapeutics, Keji Pharmaceutical, Innovent Biologics/Reindeer Medical, Ganxi Biologics, Yongtai Biologics, Legend Biologics, etc
.

In order to compete for the market opportunity of CAR-T therapy, various pharmaceutical companies do not hesitate to invest heavily in research and development, which is very similar to the situation of PD-1, and the market competition will become more and more fierce
in the future.

Unlike other innovative drugs, the cost of CAR-T products does not actually depend on the company itself
.
At present, the domestic listed CAR-T products are more expensive, mainly because they require personalized preparation, more expensive imported carriers and other materials, and the amount of product preparation is too small to form a scale effect
.
Even though the current purchase price of JW Therapeutics' relma-cel injection is 1.
29 million yuan / needle, and Fosun Kate's aquilencel injection is 1.
2 million yuan / needle, the profit margin is still very thin
for enterprises.

JW Therapeutics lost 700 million yuan in 2021, relma-cel sales of 30.
797 million yuan, sales costs as high as 21.
752 million yuan, gross profit of 9.
045 million yuan, gross profit margin of only 29.
4%, including R&D, management and other expenses, instantly broke through the cost line
.

Although in the 2022 half-year report, JW Therapeutics stated that its gross profit margin in the first half of the year had risen to 35.
0% through the implementation of the cost reduction plan, only 77 prescriptions
were issued in the first half of the year.

"Drug discovery and commercialization are two logics
.
" The market view is that many good products developed in clinical practice have not achieved good commercial results in the end, and CAR-T is facing the same test
.

If you can enter medical insurance, it is obviously the most direct way to
solve the market accessibility of innovative products and improve the coverage of commercial terminals of products.
However, China's basic medical insurance has the characteristics of wide coverage and low security, unless the price is actively reduced, it is impossible for medical insurance to pay for drugs exceeding one million yuan a shot in the short term
.

In fact, it is not easy
for CAR-T products to obtain medical insurance support and obtain a broader space through medical insurance negotiations.
In July this year, the official WeChat account of China Medical Insurance, a magazine under the supervision of the National Medical Insurance Bureau, published articles entitled "Misunderstandings in Discussing the Pricing of Drugs for Rare Diseases" and "Several Suggestions on the Protection of Drugs for Rare Diseases in China", which directly pointed to the phenomena
of "high sales costs", "avoiding medical insurance welfare", "inflated drug prices" and "stubborn diseases".

Compared with the legendary creatures that conquered the US market, while the price is higher, it also gains more patients; The domestic CAR-T product research and development end is limited in volume and payment, and commercialization is difficult
.

Industry insiders predict that with the enhancement of domestic innovation strength, the increasingly fierce competition in the domestic market, and the attractiveness of the overseas innovative drug market, more and more Chinese innovative drugs will choose to go overseas and actively embrace international competition
in the future.