Anti-CD20 mono-anti-kop: from a generation of litoxitostos to three generations of attozhu.

. The most familiar anti-CD20 monoid is rituxix from Roche (commodity name: Merofa), since its inception, the combination of rituxix and chemotherapy drugs has become the standard treatment for certain types of non-Hodgkin's lymphoma, but CD20-targeted mono-drugs are far more than Ritoxi, but Ritus has been a great commercial success.

CD20-targeted antibody drugs can be divided into three generations: the first generation of litoxi, forimo monosar, rat source or chimeric monosar;

at present, China's market anti-CD20 monoanti-resistance only Melohua, there are more than a dozen pharmaceutical companies in the development of anti-CD20 monoantinosis, but also basically are litoxial biological analogues, domestic anti-CD20 monoantinos listing will not only break the monopoly situation of Merlot, is expected to be because of its price advantages, gradually improve the penetration of anti-CD20, see the following in-depth report.

1) CD20: B cell surface protein, from the
of B cells to mature B cells expression

CD20 (Cluster of 20) is a transmembrane phosphorus protein located on the surface of B lymphocytes. B lymphocytes are differentiated by pluripotent stem cells in the bone marrow and develop through several stages: pro-B cells (Pro-B), pre-B cells (Pre-B), immature B cells (Immature B) and mature B cells (Mature B). Mature B cells are released into lymphatic tissue and can continue to differentiate into plasma cells (Plasma Cell). CD20, as a surface antigen of B cells, appears in the pre-B cell to mature B-cell stage, but CD20 is not expressed in hematopoietic stem cells, progenitor B cells, and mature plasma cells. In humans, CD20 surface antigens are encoded by the MS4A1 gene.

in addition to expression in normal B cells, CD20 is also expressed in B-cell-derived tumor cell expression, as well as in B cells involved in immune and inflammatory diseases, so CD20 antigens become targets for the treatment of diseases such as lymphoma, leukemia and certain autoimmune diseases. 2) anti-CD20 monotoreactor and three mechanisms of action related: ADCC, CDC and direct effect

CD20 target monoclonal antibodies, referred to as anti-CD20 monotom. Although the function of CD20 is not entirely clear, there is evidence that tumors from anti-CD20 monoanti-killing B cells are related to three mechanisms of action: antibody-dependent cytotoxicity (ADCC, Antibody Dependent Cell Mediated Cytotoxicity), complement-dependent cytotoxic (CDC, Dependent Cytotoxic), and direct effects caused by antibody binding to CD20 molecules, including inhibition of growth, altercell cycles and apoptoidal.

Figure 2: Anti-CD20 mono-resistance mechanism


after 20 years of time, anti-CD20 mono-resistance rapid development, the current CD20 target of the single resistance including litoxiin monoantinos (commodity name: Merova), forimo monogenic (commodity) Names: Zevaling), Tosimo Monox (commodity name: BEXXAR), Ofamu monosar (commodity name: Arzerra), Oreju monosar (commodity name: Ocrevus), and Atoju monosar (commodity name: Gazyva). Areas of treatment include lymphoma, leukemia and certain autoimmune diseases.

、CD20:

CD20,CD20、,,Fc,CD20:,,CD20,Fc。

1) First generation anti-CD20 monoid: Ritusxi pioneered targeted treatment of B-cell lymphoma

in 1997, the world's first anti-CD20 monoantivirus ritus roche rituxima, is also the world's first listed anti-tumor monosar, for the treatment of relapsing or difficult-to-treat inert lymphoma.

lymphoma is used to refer to tumors that originate in lymphatic tissue, and according to pathological classification, it is classified as Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (Non-Hodgkin's Lymphoma, NHL), about 80-90% of lymphomas belong to the latter. Most non-Hodgkin lymphomas are B-cell lymphomas. The most common NHL are diffuse large B cell lymphoma (Diffuse Large B Cell Lymphoma, DLBCL) and follive lymphoma (Follive Lymphoma, FL). DLBCL is an invasive B-cell lymphoma, which affects about 30% of the NHL; Common NHL types include marginal B-cell lymphoma( small lymphocytic lymphoma (Small lympytic lymphoma, SLL) and condom cell lymphoma.

Figure 3: Classification of non-Hodgkin's lymphoma


rituxice (commodity name: Merova) is a human rat-encrusted monosar, with a variable region of rat source and a constant area of human origin. Founded by IDEC Pharmaceuticals (currently Biogen), it was first launched in the U.S. in 1997 and with global sales of $7.2 billion in 2016, with a COMPOUND growth rate of 2% over the past five years, ranking fifth in global drug sales, and the U.S. market of Litox was jointly promoted by Biogen and Roche.

is the world's first approved monoclonal antibody for non-Hodgkin's lymphoma, and currentFDA-approved indications include non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), and Wegener's granuloma (WG) and microscope polyhevadrinis (MPA). Litoxi pioneered targeted treatment of lymphoma, and traditional chemotherapy drugs were a first-line treatment for lymphoma until rituschi. At present, the combination of the litoxiand and chemotherapy drugs CHOP (cyclophosphamide, polyphospha, Changchun neonicotinoids, strong pines) and CVP (cyclophosphamide, Changchunneoline, strong pine) has become the standard treatment options for diffuse large B-cell lymphoma and fissyl lymphoma, respectively.

the first generation of anti-CD20 monotonic, in addition to the heavy product ritus, including rat-source monoantiapizumab (commodity name: Zewarin), The world's first radioactively labeled monoantiapiate, first developed by IDEC, in the United States in 2002, was approved for treatment of relapsed B-cell non-Hodgkin lymphoma.

Zevaren is an anti-CD20 monotorine marked with radionuclide niobium 111 (In-111) or niobium 90 (Y-90). When an anti-CD20 monoclonal antibody carrying radionuclide 111 or niobium 90 is injected into the patient's body, the monoclonal antibody binds to mature B-cell and B-cell tumor cells expressing CD20, killing the cells by radioactive nuclide release radiation. Zevaren is currently acquired by Spectrum Pharmaceuticals, Inc. Sales in 2016 were about $10 million.

the first generation of anti-CD20 mono-resist also includeGSK's Tosimomo monoab (product name: Bexxar), the rat source monoab, originally developed by the manufacturer Corixa, and later purchased by GSK. Similar to Zevallin, Tosimo monosar is also connected by monoantithing, monoantigen and radioactive molecule iodine 131, for the treatment of recurrent or refractive follicles or deformed non-Hodgkin lymphoma. It went public in the U.S. in 2003, but in 2014 GSK stopped selling in the U.S. market because of a sharp drop in demand in the U.S. market.

Table 1: First generation anti-CD20 mono-resistance comparison

general name

product samen



type of


indications



Litoximab

melowah

Biogen and Roche Pharmaceutical
The

$7.2 billion in 2016

the NHL, CLL, RA, Wegener granulated (WG) and microscope polyhemorhitis (MPA)




Zevae
tan
.
Spectrum Spectrum, Inc. Inc.
.
the
of the rat source single resistance
. $10 million
2016
NHL



Tositumomab

BeXXAR

GSK

rat-source mono-anti-

GSK stopped selling in the U.S. in 2014


THE NHL




the first generation of anti-CD20 mono-resistance is a rat source monoresistance or chimeric monotoresist, the degree of human origin is not high, some patients will produce drug resistance or adverse reactions, therefore, the second generation of higher degree of human enatured sing-it gradually into the market.

2) Second generation anti-CD20 monotoresist: Humanized monoto-resistance
represented by Ofamu monototagre
was approved by the FDA in 2009 and is listed in the United States by Genmab Inc.'s Ofamu monosar (commodity name: Arzerra), which is also the first all-human source anti-CD20 monotogenic, chronic lymphocytic leukemia (CLL). Arezza was originally promoted by GlaxoSmithKline and Genmab, and was replaced by Novartis in 2016. Arezza's global sales in 2016 were $57 million, down 19 percent from 2015, and were hit by strong rival Ibrutinib. 2016FDACLL,CLL。 However, Genmab remains confident about the future of of of Ofamumono, which is currently undergoing two Phase III clinical trials in the field of alfamumonotox in the field of multiple sclerosis (MS) in an attempt to expand its indications and is expected to see results in 2019.

the second generation of anti-CD20 mono-resistant approved listing also includes Roche's human-derived monoanti-trump Oriju (commodity name: Ocrevus). The listing of Auriju has iconic significance. Auriju is the first product to achieve breakthrough therapies in the field of multiple sclerosis for the treatment of recurrent multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS), while Ocrevus is the first drug to treat PPMS. It landed in the U.S. market in March 2017.

multiple sclerosis is a central nervous system disease that affects about 2.5 million people worldwide and there is no cure for the disease. Ocrevus's successful listing is based on its positive results in three Phase III clinical trials (OPERA I, OPERA II and ORATORIO). Ocrevus is on track to generate $3.3 billion in sales by 2021, making it the next big drug, according to Clarivate, a data analytics firm.

is currently working on the second generation of anti-CD20 monoidat, as well as Veltozumab, a human-derived monotomatogenic developed by Immunomedics, which includes non-Hodgkin's lymphoma, CLL, immunoplatelet almost areduced disease, and more. In 2015, the FDA qualified vitozumab as an orphan drug in the field of immune platelet reduction.

Table 2: Second generation anti-CD20 mono-resistance comparison



general name

product name

manufacturer

type
of
sales

indications



in the U.S.



Ofatumab
.