More than 1.2 million CAR-T needles or price cuts?

The 2018 Nobel Prize in Physiology or Medicine was awarded to American immunologist James Allison and Japanese immunologist Shusuke Honjo for their contributions to tumor immunology
.

Since then, with the participation of numerous pharmaceutical companies, the era of global immunotherapy has officially opened

However, the small indication and high price make this immunotherapy rookie slightly weak in the "last mile" of market expansion
.

Studies have shown that immunotherapy has the characteristics of diversification and multi-functionality, which brings a wide range of research and development and transformation space to the industry.
PD-1/PD-L1 immune checkpoint inhibitors and CAR-T cell immunotherapy are progressing rapidly.
two areas of achievement
.

According to incomplete statistics, at present, nearly 20 PD-1/PD-L1 inhibitors have been approved for marketing in the world, involving more than 100 indications, covering more than 10 tumor types, and more than 2,000 clinical trials are still in progress
.

With the entry of many players, the global PD-1/PD-L1 market has long been a boat in the red sea.

Since 2018, tumor immunotherapy has developed explosively in China.
Most of the 11 approved PD-1/PD-L1 inhibitors are suitable for advanced NSCLC, metastatic melanoma, classic Hodgkin lymphoma The three CAR-T cell immunotherapies can be applied to hematological tumors such as lymphoma and multiple myeloma
.

Judging from the number of product approvals, domestic tumor immunotherapy closely follows the pace of international development and has become the second largest market after the United States, and there are still more than 500 cell therapy projects in the clinical research stage
.

As we all know, the objective reality of CAR-T cell therapy based on R&D cost, production process and individualized treatment leads to its high price.
The price of 8 CAR-T therapies that have been listed so far exceeds one million yuan, far exceeding the charging standard of traditional treatment.
This directly leads to a small base of patients who can afford the therapy.
Judging from 21 years of sales data, these 8 products are far below the $1 billion sales standard of blockbuster products
.

The 8 CAR-T therapies currently on the market are priced at over one million yuan, far exceeding the charging standard of traditional treatments

The two CAR-Ts listed in China have achieved sales of less than 100 million yuan.
Among them, Fosun Kite’s Akilunsai (Yikaida) serves no more than 100 patients and has a revenue of less than 100 million yuan.
; WuXi Junuo's Ruiki Orenza (Benoda) issued a total of 54 prescriptions, with a revenue of 30.
8 million yuan
.

Globally listed CAR-T cell therapy and 21 years of sales (organized by Shell)

But this result is also predictable
.

On the one hand, the approved CAR-T cell therapy is limited to smaller indications.

On the other hand, the pricing is too high, and under the background that China's per capita deposit does not exceed 100,000 yuan, there are very few consumers who can afford more than one million yuan
.

The financial report disclosed by WuXi Junuo shows that the gross profit of Benoda in 2021 will be 9.
045 million yuan, and the total R&D and sales expenses will be 585 million yuan, which is 19 times the revenue
.

This also means that for companies, domestic CAR-T cell therapy still has a long way to go before it is truly profitable

The road to profitability is still difficult, and peer competition has begun
.

The road to profitability is still difficult, and peer competition has begun
.

At present, the five CD19-targeted CAR-T cell therapies that have been approved and marketed in the world can all be used for the same indication of relapsed or refractory large B-cell lymphoma, and the competition is fierce
.

Looking at China, as of the end of 2021, more than 30 CAR-T products from more than 20 companies are in the market application stage, and more than half of them are CD19-targeted therapy for malignant hematological tumors

Similar to PD-1/PD-L1, domestic CAR-T will also face homogenization competition due to oversaturation
.

Also as a tumor immunotherapy, the PD-1/PD-L1 market has stabilized through price cuts, access to medical insurance, expansion of new indications, and combination drugs.
It seems that CAR-T can also successfully transition by referring to this model, but considering CAR-T Due to the special attribute of overpriced itself, price reduction has become the key to stabilizing the market and continuing to expand
.

So can the price of CAR-T be reduced in the future?

Medical insurance and commercial insurance double "insurance"

Medical insurance and commercial insurance double "insurance"

It is reported that the price of Novartis' first CAR-T therapy was questioned when it first broke out.
In order to solve the accessibility of "sky-priced drugs", the US Centers for Medicare and Medicaid Services (CMS) agreed to include CAR-T therapy in medical insurance.
Reimbursement, and proposed a pay-for-efficacy strategy, that is, Novartis may receive CMS reimbursement at the end of the month only if the patient responds to CAR-T therapy in the first month
.

Since then, Canada, the United Kingdom, Japan, etc.

Of course, this kind of medical insurance scheme may also be realized domestically in the future
.

However, due to the large population base in China, it is difficult for medical insurance funds to pay for the high cost of cell therapy in the short term

In recent years, with the increasing number of cancer patients, in addition to medical insurance, commercial insurance has also begun to enter the field of anticancer drugs
.

At present, Gilead's Yescarta has been actively exploring in the field of commercial medical insurance, and said that most commercial insurances are willing to pay for related treatment costs, among which the payment terms between commercial medical insurance and patients are based on individual contracts, which means that in eligible Under these circumstances, the insurance company may bear the full cost of the patient's treatment
.

It is worth mentioning that shortly after the approval of the first CAR-T product in China, commercial insurance companies represented by Ping An announced its entry into the field of CAR-T cell therapy
.
Subsequently, Huimin Insurance in many places, as well as commercial insurance such as Zhongan Insurance and Taikang Insurance, included CAR-T therapy in the scope of reimbursement
.
Among them, Jinghuibao and Suhuibao only need to pay 79 yuan a year, and can obtain a reimbursement amount of up to 1 million yuan for CAR-T therapy, which greatly reduces the burden of patients on medication
.

At present, Fosun Kite's Yikaida has been included in urban Huimin Insurance and over 40 commercial insurances in 23 provinces and cities
.
WuXi Junuo's Benoda has also covered 44 commercial insurance and 16 municipal supplementary medical insurance plans
.

Although, in November 2021, the 1.
2 million akirenza injection was blocked from the negotiation of the medical insurance catalogue, but in the future, after the relevant policies are completed, CAR-T drugs are likely to be successfully accepted by medical insurance
.
At that time, when domestic CAR-T was fully included in medical insurance and commercial insurance, it was equivalent to a disguised price reduction for patients
.

Process re-optimization

Process re-optimization

Since the late 1980s, CAR-T has completed six technical iterations, but there are still certain technical bottlenecks
.

At present, CAR-T cell therapy belongs to autologous cell therapy.
Each cell is only aimed at an independent individual.
The production, storage, reinfusion, transportation and other processes of cells require different process designs, resulting in extremely high cost of this therapy
.
And UCAR-T (universal CAR-T therapy) has the advantages of industrialized mass production, short cycle and low cost.
It is called off-the-shelf CAR-T therapy and can be used for the treatment of solid tumors at the same time
.

According to statistics, only 10% of tumors are hematological tumors, and the remaining 90% are solid tumors, and there is a huge unmet clinical demand .
Began to use the more mature production and design process of CAR-T in hematological tumors to deploy solid tumors
.

The remaining 90% are solid tumors with huge unmet clinical needs,

Innovent's universal IBI345 CAR-T therapy completed the first patient dosing in a clinical trial for the treatment of advanced Claudin18.
2-positive solid tumors, and Beiheng Bio's CTA101 has also been approved for clinical use in the treatment of adults with relapsed or refractory disease B-cell acute lymphoblastic leukemia (r/r B-ALL), if the above products are approved, the price of CAR-T drugs will be further reduced
.

In addition, non-viral vector CAR-T is also a popular research direction for CAR-T cell therapy at present, and it is expected to solve the dependence of CAR-T cells on viral vectors in the future and directly reduce costs
.

Compared with the sixth-generation CAR-T, the fifth-generation TCR-T has more advantages in the treatment of solid tumors, but there are two major problems in identifying the TCR sequence and improving the affinity of TCR-pMHC.
T is expected to become another blockbuster new drug for solid tumors
.

After the technology iteration, along with the decline in production costs, cell therapy will enter the market again with the advantage of price reduction
.

foray into new territory

foray into new territory

At present, although CAR-T cell therapy is very hot in the field of hematological tumors, due to the lack of ideal target antigens, the immunosuppressive microenvironment (causing T cell exhaustion, poor tumor infiltration), and treatment-related toxicity and other limiting issues, it is not widely used in the field of solid tumors.
Progress is slow
.

Recently, it was reported that the Third Xiangya Hospital of Central South University in China said that it has made a breakthrough in the field of CAR-T immune cell therapy for advanced liver cancer.
The metastases disappeared, and the working ability has now been restored
.

Coincidentally, Carl June and others from the University of Pennsylvania also published the results of the first phase 1 clinical trial of CAR-T therapy for solid tumors in Nature.
The results showed that anti-TGF-β CAR-T cell therapy for solid tumors is feasible, and It is generally safe and promising for the treatment of metastatic castration-resistant prostate cancer (mCRPC)
.

The above indications indicate that CAR-T is expected to achieve breakthrough progress in the field of solid tumors
.

The above indications indicate that CAR-T is expected to achieve breakthrough progress in the field of solid tumors
.

At the same time, Nature issued a document pointing out that when the CAR-T therapy axicabtagene ciloleucel (Axi-cel) was used as a first-line therapy for the treatment of patients with large B-cell lymphoma (LBCL), it showed a very high complete remission rate, and the estimated post-treatment 1 The annual overall survival rate was 91%
.
While the existing chemotherapy for LBCL needs to last about 6 months, CAR-T therapy is expected to achieve the effect of shortening the treatment time while improving the treatment effect of hematological tumors
.

With the continuous expansion of indications, it directly brings about a positive expansion of the market
.
Under the regulation of the market, CAR-T therapy is expected to usher in a new round of price cuts
.

postscript

postscript

On the whole, with the continuous expansion of CAR-T indications in the field of solid tumors and hematological tumors, coupled with the multiple effects of cost control and cost reduction, the price trend of CAR-T cell therapy can refer to PD-1/L1 monoclonal antibody.
(From the initial hundreds of thousands per year to tens of thousands per year, and then to the control of medical insurance prices)
.
Therefore, we believe that the price of CAR-T cell therapy will gradually decrease from the high price, and eventually become an affordable new anti-cancer drug for patients with the joint efforts of all parties
.

However, considering that there are certain barriers to process optimization and the current situation of limited medical insurance funds, for CAR-T therapy, commercial insurance may be the most effective way to reduce prices in the short term
.
In the near future, with the continuous expansion of commercial insurance promotion, a larger group of patients will be able to enjoy the benefits of the era brought by modern medical care
.