The past and present of the first biosimilar drug rituximab included in the collection

More than 20 years ago, Rituximab was the world's first marketed anti-tumor monoclonal antibody; more than 20 years later, as the first biosimilar drug in China to be included in centralized procurement, the topic of Rituximab has not decreased
.
01 Origin: CD20 target Rituximab is a human-mouse chimeric monoclonal antibody synthesized by genetic engineering technology.
It consists of human IgG1kappa constant region and mouse CD20 antibody variable region
.
Rituximab can specifically bind to the transmembrane protein CD20 on the surface of B cells, and kill CD20-positive B lymphocytes through two pathways, antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

.
CD20 (Cluster of Differentiation20) is a transmembrane protein located on the surface of B lymphocytes
.
B lymphocytes are differentiated from pluripotent stem cells in the bone marrow and develop through progenitor B cells (Pro-B), pre-B cells (Pre-B), immature B cells (ImmatureB) and mature B cells (MatureB).
a stage
.
Mature B cells are released into lymphoid tissues and can continue to differentiate into plasma cells (PlasmaCell)
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As the surface antigen of B cells, CD20 appears in the stage of pre-B cells to mature B cells, but CD20 is not expressed on hematopoietic stem cells, progenitor B cells and mature plasma cells
.
In addition to being expressed in normal B cells, CD20 is also expressed in B cell-derived lymphomas, leukemias, and other tumor cells, as well as in B cells involved in immune diseases and inflammatory diseases, so CD20 antigen becomes lymphoma, leukemia and some Targets for the treatment of autoimmune and other diseases
.
Although attacking tumor cells with CD20 protein will also kill normal B cells by mistake, but the side effects are relatively controllable
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02 Overview of indications As the world's first monoclonal antibody targeting CD20, rituximab has been approved for 15 indications so far, of which 7 indications are concentrated in the field of lymphoma and lymphocytic leukemia, 8 indications and Immune diseases are associated with inflammatory diseases, and 3 additional indications are in preclinical and clinical development
.
Source: CPM New Drug Development Surveillance Database Lymphoma is used to refer to tumors originating from lymphoid tissues.
According to pathological classification, it is divided into Hodgkins Lymphoma (HL) and Non-Hodgkins Lymphoma (NHL) Two, about 80%-90% of lymphomas belong to the latter
.
Most of these non-Hodgkin lymphomas are B-cell lymphomas
.
The most common NHLs are diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL)
.
DLBCL is an aggressive B-cell lymphoma, about 30% of NHLs belong to this type; follicular lymphoma is an indolent lymphoma, about 25% of NHLs belong to this type
.
03 Rituximab, the predecessor of Rituximab, was originally developed by RochePharma (Schweiz) Ltd.
and was approved by the US FDA in 1997.
Rituximab was launched in China in 2000 under the trade name of Rituxan.
The approved indications For non-Hodgkin's lymphoma and chronic lymphocytic leukemia
.
It is worth noting that the annual cost of rituximab plus chemotherapy after approval is more than 200,000 yuan.
The domestic market is limited by the high price and the overall growth of the scale is limited
.
In 2017, rituximab was included in the national medical insurance category B catalog.
With the inclusion of medical insurance, the out-of-pocket part of rituximab was reduced to about 30,000 to 40,000, and the market size began to rise significantly.

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According to PDB domestic sample hospital market data, the annual sales volume of rituximab (Rituximab) exceeded 100,000 bottles for the first time.
After being included in the medical insurance, the sales volume of Rituximab exceeded 200,000 bottles in only 1 year, and the medical insurance increased the volume.
Obvious
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Source: CPM New Drug Research and Development Monitoring Database Figure 1 Sales volume of Rituxan over the years (2012-2018) Rituxan's Chinese patent expired in 2013, and many domestic and foreign pharmaceutical companies have joined its biosimilar research and development
.
Shanghai Fuhong Henlius Biopharmaceutical Co.
, Ltd.
's Rituximab Injection (Hanlikang), approved by the National Medical Products Administration (NMPA) in February 2019, is the first rituximab approved in China Biosimilars
.
At the end of September 2020, the second domestic rituximab was approved for marketing, with the trade name Dabohua, from Innovent Biopharmaceutical Co.
,
Ltd.
According to the CPM new drug research and development monitoring database, Chia Tai Tianqing's rituximab injection is already under marketing approval and is expected to be approved in the near future
.
The price of biosimilars is more determined by the production cost than the R&D cost, which is about 30%-50% lower than the original research drug
.
Lower prices make it affordable for more patients, and the domestic rituximab market has grown year by year
.
Source: CPM New Drug Research and Development Monitoring Database 04 Rituximab's Life Because the price of rituximab changed before and after being included in the medical insurance, and the prices of biosimilars and original drugs of different companies are also inconsistent, we mainly use rituximab The sales volume, combined with the sales volume, analyzes the current domestic market size of rituximab
.
Unless otherwise specified, the hospital-side market data used in this article are all from the PDB comprehensive database, and the sales quantity is measured in the smallest unit of 1 bottle
.
Figure 2 Sales volume of rituximab manufacturers over the years From Figure 2, it can be seen that the rituximab of Henlius entered the market in rapid volume
.
From 2019 to 2021, in just two years, Hanlikon's sales volume exceeded that of Rituxan
.
Part of Hanlikang's market share is to seize the original market of Rituxan, and the other part is to open up new markets by reducing prices and increasing volumes
.
Because it uses the same generic name as the original drug, Hanlikang can directly enter the medical insurance after being approved
.
Judging from some public data, after Hanlikang was approved for listing, it was launched in Guangxi, Guizhou and other places at a price of 1,640 yuan per stick.
This price has dropped by about 30% compared with the medical insurance price of Rituxan
.
On July 30, 2019, 5 months after the approval, Henlius adjusted the winning bid price of rituximab (100mg/10ml) from 1,640 yuan/bottle to 1,398 yuan/bottle, a drop of 14.
8%
.
Fuhong Henlius then took Roche's army and achieved a counter-attack from the second to the first through the price war
.
Figure 3 Sales growth of rituximab manufacturers over the years However, it can be seen from Figure 3 that Roche's Rituxan still ranks first in overall sales
.
Henlius has only completed a quantitative counterattack so far.
Whether the quantitative change can lead to a qualitative change still needs time and the market to further verify
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Due to its late approval, Innovent Bio’s Dabohua currently occupies a limited market share
.
However, in the volume procurement of Guangdong Alliance that just ended last week, rituximab was included in the centralized procurement, and Innovent Bioforced Roche and Henlius to win the proposed selection with the sincerity of 885.
8 yuan per bottle
.
The market always comes first to eat meat and later to drink soup, especially in the pharmaceutical market due to the stickiness of patients and the habits of doctors' prescriptions
.
To a certain extent, centralized procurement has given enterprises an opportunity to reshuffle their cards.
This move by Cinda Biology can be regarded as a last-ditch battle.
We will wait and see whether it can make a breakthrough
.
More than 20 years have passed since the first anti-tumor monoclonal antibody was launched to the first time that biosimilars were included in the collection.
During this period, many original monoclonal antibodies and biosimilars have been launched one after another, prolonging the lives of tumor patients and bringing about Hope for healing
.
We look forward to the development and launch of more new drugs and generic drugs in the future, which will elevate national health to a new level
.