Analysis of the current status and future prospects of China's targeted drug market in 2018

Source: China Report Network

        A targeted drug (also referred to as a targeted formulation) refers to a drug or a formulation thereof that is endowed with the ability to target. The purpose is to enable the drug or its carrier to target a specific lesion and accumulate or release the active ingredient at the target site. The targeted preparation can make the drug form a relatively high concentration in the target part, thereby suppressing the toxic side effect and reducing the damage to the normal tissue and cells while improving the drug effect.

        Depending on the target, drug targeting can be divided into several levels:

        1. Organ and organ level: The drug can be selectively accumulated in tumor tissues, inflammation sites, or specific organs such as heart, liver, spleen and lung, thereby reducing systemic adverse reactions. At present, targeted chemotherapy drugs for tumor tissues are a hot topic of research. For example, targeted drugs designed for specific environments such as tumor hypoxia, low pH, and neovascular density can increase the concentration of drugs in tumor tissues and significantly improve tumor chemotherapy. effect.

        2, cell level: the use of certain receptors on the surface of diseased cells, on the surface of the drug or its carrier to modify the ligand specifically binding to the receptor (such as antibodies, peptides, sugar chains, nucleic acid aptamers, or other small Molecules, etc., enable the drug to accurately locate and kill the diseased cells without causing significant toxic effects on normal cells.

        3. Subcellular levels: Many drugs (such as nucleic acid drugs, most protein drugs, and some small molecule drugs) need to enter the interior of the cell or function in specific organelles (such as mitochondria, nucleus). Transmembrane peptides, nuclear localization sequences, etc. are currently the most targeted components.

         The main targeted therapeutic drugs used in clinical practice are based on the theory of apoptosis, which prevents or initiates the conduction process of a certain cell signal, thereby inhibiting tumor proliferation and inducing it to enter the apoptotic process. Related to cell proliferation and apoptosis mainly include two genes and two cell signaling pathways.

        The process of cell signal transduction is based on a series of phosphorylation processes of specific proteins. The mechanism of action of monoclonal antibodies and small molecule targeting drugs is to target specific protein targets during cellular signaling. For example, cell proliferation and division do not occur without any reason. There is a protein factor in the human blood called epidermal growth factor (eg, egf); and there is a transmembrane protein on the cell membrane. The so-called transmembrane protein is a kind of floating on the cell membrane. A macromolecular protein that has a portion of its structure exposed to the outside of the cell membrane and a portion of its structure hidden inside the cell.

      The mechanism of action of monoclonal antibodies and fentanyl small molecule targeting drugs is to selectively bind to specific proteins involved in cell signaling processes, thereby blocking the conduction process of cellular signaling pathways. The chemical nature of monoclonal antibodies is macromolecular proteins. The chemical nature of trinesic drugs is a class of small molecular organic compounds, which usually contain a specific chemical structure, such as a quinazoline (a heterocyclic compound containing a nitrogen atom). One type of tritin is an effective inhibitor of egfr.

        At present, molecular mechanisms such as multiple gene mutations and abnormal expression have also been confirmed to be associated with the pathogenesis of NSCLC. Drugs designed to drive gene mutations are currently referred to as targeted drugs.

       EGFR mutation is the most common driving gene of NSCLC. About 17% of NSCLC patients have EGFR mutations, and the probability of mutation in Asian countries such as China is more than 30%. EGFR-TKIs competitively bind to EGFR through endogenous ligands, inhibit the activation of tyrosine kinases, thereby blocking the EGFR signaling pathway, and ultimately produce a series of biology that inhibit tumor cell proliferation, metastasis and promote tumor cell apoptosis. effect.

        Several large phase III clinical trials have demonstrated that EGFR-TKIs are superior to chemotherapy in the treatment of EGFR mutation-positive NSCLC, so almost all guidelines recommend EGFR-TKIs (eg gefitinib, erlotinib, ectinib) as A first-line treatment regimen for EGFR mutation-positive NSCLC.

        For patients with EGFR mutations screened by gene sequencing, EGFR-TKIs are superior to traditional chemotherapy drugs in terms of objective progression rate and side effects, regardless of median progression-free survival (the most important indicator of patient survival quality). This is also a better interpretation of precision medicine, the most useful drugs are used in the most needy patients, only patients with EGFR mutations can take effect, otherwise the effect is not as good as chemotherapy drugs. The huge population of cancer patients also brings great market value.

        With the intervention of many first-generation EGFR-TKIs, and the existence of many factors such as drug resistance, the market has become weak and began to decline. To know that the growth rate of NSCLC's entire field is as high as 16%, in this wave, the first generation of EGFR-TKIs may only sigh: the sunset is infinitely good, just near dusk! But this is a boon for Chinese patients, with up to 30% of EGFR mutations and a large patient base. These people wait for drugs to save lives just like the babies waiting to be fed. Although the first targeted drug has a significant effect, two-thirds of patients will develop drug resistance for 1-2 years.

        At present, there are still a large number of tumor-targeted drugs in China, which are in the research or clinical stage. With the market of these drugs, the clinical targeted drugs will be greatly expanded, which is expected to drive the rapid development of related gene detection target industries. Although the clinical use of drugs in China and the United States is different, we expect that the number of domestic tumor-targeted drugs will expand significantly in the future, which will directly stimulate the substantial expansion of the tumor-associated diagnosis market.

        Source: Guanyan Tianxia (YZ)