"One year's anti-cancer drug fee is equivalent to the money I pay off my mortgage with interest." When countless patients with advanced lung cancer said this, their eyes were already moist. The high cost of targeted drugs has become a heavy burden for them and countless cancer patients.
Are we doomed to a painful choice between chemotherapy and poor treatment?" Why can't the price of sky-high "targeted drugs" be reduced?
1. What is a targeted drug?
Targeted drugs are a new concept compared to traditional chemotherapy drugs, which refers to the design of drugs that can precisely act on tumor cell-specific targets by studying the molecular mechanism of tumor cell growth. Targeted drugs are highly selective and can accurately act on the critical path of tumor cell growth, so as to achieve the purpose of inhibiting tumor growth.
Unlike traditional chemotherapy drugs, targeted drugs have the characteristics of "precision strike". Traditional chemotherapy drugs mainly inhibit all rapidly dividing cells by destroying cellular DNA, so they can not only kill cancer cells, but also produce certain toxic side effects on normal cells. The goal of targeted drugs is to act specifically on cancer cells to minimize damage to normal cells.
The research and development of targeted drugs is inseparable from the in-depth study of the mechanism of tumorigenesis and development. Taking common breast cancer as an example, its occurrence is related to the inactivation of multiple proto-oncogenes and tumor suppressor genes, such as ERBB2, PI3K and BRCA1/2. The oncoproteins encoded by these oncogenes often play a key role in signal transduction pathways and can serve as focal points for targeted drugs.
The HER2 protein encoded by the ERBB2 gene is a transmembrane receptor tyrosine kinase, and overexpression will promote the downstream effects of the EGFR signaling pathway and promote the proliferation of tumor cells. The target of drugs such as fentanyl and trastuzumab is HER2 protein, which can inhibit its binding to ligands and block downstream signaling and inhibit tumor growth.
In addition to single-target drugs, a number of complex multi-target drugs have also been developed. For example, lapatinib simultaneously inhibits VEGFR and EGFR receptor tyrosine kinase, which can better exert anti-tumor effects.
Some cell cycle-relevant targets, such as CDK4/6, have also been targeted for drug design. CDK4/6 inhibitors such as abexol and pembotinib can inhibit cell cycle progression for the treatment of advanced HR+/HER2- breast cancer.
With the deepening of tumor biology research, it has been found that the abnormal pathways driving tumorigenesis are far more than tyrosine kinase receptors, so the range of targeted drugs is also expanding.
For example, the PARP inhibitor olaparil can be used for breast and ovarian cancer caused by BRCA gene defects. mTOR inhibitors such as raleon and canseirozumab are also used to treat hormone receptor-positive advanced breast cancer.
The advent of immunosuppressants has brought new opportunities for tumor immunotherapy, which enhance the body's anti-tumor immune response by blocking the immune escape mechanism of tumor cells.
For example, inhibitors such as pembrolizumab and nivolumab can be used in combination with targeted small molecule drugs to achieve synergistic antitumor effects. CAR-T cell therapy acts on tumor antigens and initiates immune cells to kill tumors by targeting tumor antigens, which is also a kind of tumor targeted therapy.
Targeted therapy has opened a new era of precision medicine for tumors. With the deepening of biological research, we are expected to discover more pathogenic mechanisms of tumors and corresponding therapeutic targets. Targeted drugs will also be expanded to a wider range, making the treatment of tumors more accurate and effective. But its price is high, why can't the country bring down the price of high-priced targeted drugs?
Second, the price of targeted drugs is high, why can't the price be reduced?
The high price of targeted drugs is mainly due to the following reasons:
1. Huge investment in targeted drug research and development
It takes at least 10 years for new drugs to go from initial design, synthesis to clinical trials, and the initial R&D investment cost is usually more than $1 billion. Most of these drug candidates have been eliminated due to poor efficacy or safety issues, and only a very small number of new drugs have been approved for marketing.
And targeted drugs are different from biological agents, can not reduce the price through generic drugs, small molecule targeted drugs have a precise chemical structure, with drug patent protection, imitation is extremely difficult, which also leads to the research and development cost of approved drugs is more expensive.
Even after the patent period ends, it is difficult to develop generic drugs with comparable quality and efficacy to the original drug, and it is necessary to design highly selective compounds for specific targets, which increases the cost of trial and error. These upfront R&D investments are eventually factored into the selling price of the drug.
2. The approval cost of imported drugs is high
Targeted drugs are usually imported drugs and need to undergo repeated clinical trials to obtain marketing authorization from mainland China. According to the regulations, all overseas drugs must re-undergo phase I or phase III clinical trials in accordance with mainland regulatory requirements to evaluate the safety and efficacy of drugs in Chinese groups. This has undoubtedly increased the cost of drug research and development again.
Clinical trials also need to pay high new drug approval fees, and some pharmaceutical companies choose to enter the Chinese market through technology transfer, which also requires paying high technology royalties.
3. High sales and transportation costs
The cost of targeted drug sales and circulation is high, most of the targeted drugs need to be imported from abroad, need to pay high tariffs and transportation costs, and various link costs are also added to the domestic drug circulation process. The hospital needs to pay the sales commission and medical compensation fee for the drug at the time of purchase. These circulation costs are included in the selling price of the drug.
It can be seen that the high price of targeted drugs has its inherent reasons, and it is not that pharmaceutical companies bid up prices out of thin air. To reduce drug prices, we must start from the R&D and approval links to improve R&D efficiency and lower the approval threshold. At the same time, expand the research and development of domestic targeted drugs and reduce dependence on imports. Only the joint efforts of many parties can fundamentally solve the problem of high price of targeted drugs.
So for patients with advanced cancer, do you have to buy expensive targeted drugs?
Third, whether it is necessary to buy expensive targeted drugs in the advanced stage of cancer
Whether advanced patients have the financial means to afford the high cost of drugs is a key consideration. According to the current medical insurance reimbursement ratio, the out-of-pocket costs of some expensive first-line courses of targeted drugs still require hundreds of thousands of millions. This is a big financial burden for many ordinary families. If the family is financially poor, careful consideration needs to be given to the value of continuing treatment.
Any drug has a range of indications, and not all patients with advanced stages benefit from targeted drugs. This requires clinical testing to clarify the patient's pathological type and target expression to judge the tolerability and effectiveness of the drug. Otherwise, the use of expensive targeted drugs is not only a waste of money, but also may affect the quality of life due to adverse drug reactions.
It is also necessary to thoroughly evaluate the advantages and disadvantages of different treatment options. In addition to the therapeutic effect, it is also necessary to consider the impact on the quality of life and the size of toxic side effects. Although chemotherapy has significant side effects, it may also be the best option for some patients whose condition worsens. The focus is on finding the most suitable treatment strategy for the patient under expert guidance, rather than blindly pursuing the most expensive targeted drugs.
Rational use of medical insurance policies can also reduce the cost of treatment. Some regions have included some targeted drugs in medical insurance reimbursement, and patients can enjoy a certain percentage of reimbursement. At the same time, the hospital also provides partial subsidies or relief funds to help patients with financial difficulties complete treatment. Rational allocation of various medical resources is also one of the ways to reduce the burden on patients.
epilogue
High-priced targeted drugs undoubtedly increase the economic burden of patients, but they play an indispensable and important role in the precision treatment of tumors. How to find a balance between ensuring the effective supply of drugs and controlling the cost of drugs requires the joint efforts of government departments, medical institutions and pharmaceutical manufacturers.
The majority of patients should also think rationally when choosing treatment, fully evaluate their own situation, and choose the most affordable treatment plan. Only in this way can we avoid the pain caused by "poor disease" while pursuing the best curative effect. We look at the development of precision medicine with hope, and we also hope that the reform of the medical system will make every life respectful.
Resources
Gu Jing, Du Haixia, Definition, classification and application prospect of targeted drugs, Journal of Jilin Medical University, December 2018
Shi Aiqun, Tan Xiaoguang, Development of Targeted Drugs and Drug Regulation, China Pharmaceutical Affairs, January 2021
Yao Chenwei, Development status, problems and countermeasures of targeted drugs, Medical Theory and Practice, March 2020