Trastuzumab Monoclonal Antibody Cancer Drug

English name：Trastuzumab

CAS number：180288-69-1

Molecular formula: C10H14N6O5

Molecular weight: 298.25536

EINECS No

Related categories: drug substance; mab 20; pharmaceutical raw material; biochemistry; chemical reagent

The Mol file: 180288-69-1.mol

Structural formula:

Trastuzumab properties

Storage conditions: Store at-20 C

Form: solid

Color: White to light yellow

Use

Trastuzumab is used in the treatment of breast cancer. It is effective against tumors that overexpress the HER 2 / neu protein. As part of a chemotherapy regimen for the adjuvant treatment of lymph node-positive, HER 2 / neu-positive cancers.

And HER 2-positive breast cancer treatment agents

Trastuzumab is the first humanized antibody drug targeting HER 2 developed by Roche Company. The main indications are HER 2-positive breast cancer and metastatic gastric cancer. The drug was FDA approved on September 25,1998, the European patent for trastuzumab expired in 2014, and the US patent for Chemicalbook expired in 2019. In 2016, the global sales of trastuzumab were 6.782 billion Swiss francs (+ 3.73%), and 5.2 CAGR 24% in the past five years, ranking 8th among the top 10 best-selling drugs in the world. We expect trastuzumab's global sales to fall to $5.66 billion in 2020 due to the launch of its biosimilar drug.

In the US market, trastuzumab-like Ogivri, Pfizer's PF-520014, Teva / Celltrion's Herzuma, and Amgen / Elgen's ABP980 have all filed listing applications with the FDA, and Roche are still filing patent lawsuits. In the European market, Samsung Bioepis Ontruzant was approved by EMA on 21 November 2017, becoming the first biosimilar trastuzumaub approved in the European Union, with indications including early and metastatic breast cancer and metastatic gastric cancer. Mylan and Bicon have delayed their approval due to production problems, and Celltrion has filed for a listing, awaiting a final review.

Trastuzumab is covered in medical insurance

Trastuzumab entered the Chinese market on September 5,2002, and the indications were HER 2-positive breast cancer and gastric cancer, under the trade name Herceptin (Herceptin). Since China is a high incidence area of breast cancer and gastric cancer, Chemicalbook and 25%~30% of HER 2 in primary breast cancer are overexpressed, trastuzumab has maintained a steady growth in China. In the past 5 years, CAGR18%, and because the expensive price has not been included by medical insurance, the market of the drug has not been fully released.

On July 19,2017, trastuzumab was listed in the national medical insurance directory, and the negotiated price of medical insurance was 7,600 yuan, a drop of 67% compared with the winning price. Because trastuital monomab is HER 2 positive breast cancer and gastric cancer first-line medication, its clinical efficacy has confirmed its "gold standard" status, as the health care price, its huge unmet market demand will prompt its rapid capacity, due to its similar drug obvious price advantage and the same Chemicalbook clinical curative effect, is expected to rapid expansion. At present, trastuzumab are breast cancer and gastric cancer. In terms of breast cancer medication, the universal treatment regimen for trastuzumab is 6mg / kg every 3 weeks (first dose 8mg / kg), and the recommended treatment time for breast cancer is at least 6-8 cycles. Assuming that the average weight of the patient is 50-70kg, the average treatment cost of trastuzumab for each patient is about 52,000 yuan.

The duration of treatment for GC was progression-free survival (PFS) with trastuzumab at 7.7 months. Assuming that the average weight of the patient is 50-70kg, the average treatment cost of each patient receiving trastuzumab is about 70,500 yuan.

Due to the price reduction of trastuzumab in medical insurance, we expect the treatment penetration rate to reach 80%. Therefore, we estimate that the market size of trastuzumab is 52.72-58.46 billion yuan, among which the market size of breast cancer and gastric cancer is 11.34-13.62 billion yuan and 41.38-44.84 billion yuan respectively. Assuming that the price reduction of biosimilar drugs is 30Chemicalbook%, with the replacement rate of 30%, 50% and 70%, the market size of biosimilar drugs is 11.07-12.28 billion yuan, 18.45-20.46 billion yuan and 25.83-28.65 billion yuan respectively. The trastuzumab biosimilars, which are expected to be marketed as soon as possible, are Fuhong Hanlin and Anke Bio, which are expected to be the first to seize the market.

Bioactivity

Trastuzumab (anti-HER 2) trastuzumab is an antibody inhibitor of human recombination that binds to the extracellular region of HER 2.MW:145.53 KD.

Target spot

Target Value

HER2

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In vitro study

Trastuzumab (anti-HER 2) exerts specific antitumor activity in tumor cells overexpressing HER 2. Trastuzumab binds to the juxtamembrane region of HER 2, and once bound to the receptor, this antibody can downregulate HER 2 expression. Trastuzumab Stively inhibits ligand-independent HER 2-HER 3 dimerization. In addition, trastuzumab binding to HER 2 inhibited lyolytic cleavage of the extracellular domain of HER 2, resulting in reduced levels of p95Chemicalbook-HER 2.trastuzumab Can lead to the downregulation of the PI3K signaling pathway and downstream cell cycle progression-related mediators such as cyclinD1. Trastuzumab Not only inhibited HER 2 signaling, but also caused immune-related responses in HER 2-overexpressing cells. Binding of Trastuzumab takes up Fc receptors on immune effector cells, leading to antibody-dependent cytotoxicity. Thus, trastuzumab has an antiangiogenic effect, lowering the chemotherapy-based apoptosis threshold.

In vivo research

Chronic administration of Trastuzumab to a range of animal models, including primates, has demonstrated that Trastuzumab is safe. In the adjuvant treatment experiment simulating submacroscopic diseases, trastuzumab was able to inhibit the growth of macroscopic detectable graft tumors with Chemicalbook for 5-7 weeks. Trastuzumab Has significant anti-tumor activity and is currently being used in the treatment of breast cancer. In an in vivo model, trastuzumab decreases microvessel density in breast cancer graft. Trastuzumab Acting directly on cancer cell signals and indirectly on the immune system.

Security information

Toxic substance data: 180288-69-1 (Hazardous Substances Data)

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