Guangdong'S First "Restricted Use" List Of Antineoplastic Drugs

On July 28, the Guangdong Pharmaceutical Association issued the guidance on the grading management of anti-tumor drugs in medical institutions of Guangdong Province (hereinafter referred to as the guidance), and issued the reference list of restricted use levels of anti-tumor drugs in Guangdong medical institutions, involving 78 drugs. The guidance will be implemented from July 27, 2021.

These two documents are the refinement of the relevant provisions of the former National Health Commission, and the grading standards have aroused heated discussion in the industry. At the end of last year, the National Health Commission updated the classification standard of restricted use level anti-tumor drugs in the "administrative measures for clinical application of anti-tumor drugs (Trial)", and required that the utilization rate of anti-tumor drugs of restricted use level and ordinary use level, and the proportion of anti-tumor drugs used amount should be included in the assessment of medical institutions《 The guiding opinions refine the division standards in the management measures.

This list involves the products of many well-known pharmaceutical enterprises at home and abroad. Recently, the reporter of 21st century economic report also contacted the relevant persons in charge of many of them, and most of them would not mention it. Some enterprises also said that they should be cautious and follow-up measures are being evaluated.

In fact, in recent years, the state has strengthened the management of the application of anti-tumor drugs through the implementation of relevant standards and management methods, and rectified the chaos in the process of drug use. However, on the other hand, the country is also vigorously encouraging drug innovation. For example, in the 2021 national medical insurance drug list, which was released on July 30 and passed the preliminary form review, many new anti-tumor drugs that have just been approved are listed.

"In general, the starting point of the policy is to standardize the use of drugs, but we also hope to have reasonable arrangements under the premise of ensuring the accessibility of patients." An industry source told the 21st century economic report, "there are too many patients, and it is unlikely that all of them will go to see the expert number. Therefore, even if it is a product with better curative effect and cheaper price, the patient may not use it. In fact, it may be different from the national policy of encouraging innovation, accelerating access and improving patient access."

Hot discussion on New Deal

Since 2018, the National Health Commission has issued relevant regulations every year to refine the clinical management of new anti-tumor drugs. The "guiding opinions" issued by Guangdong Pharmaceutical Association is also a further refinement of the relevant policies of the National Health Commission.

According to the guidelines for clinical application of new anti-tumor drugs (2019 Edition) organized by the National Health Commission, the anti-tumor drugs are divided into two levels of common use and restricted use according to whether they have been listed in the national essential drug list or the national essential medical insurance drug catalogue or the national negotiated drugs according to the drug indications, drug accessibility and cancer treatment value.

However, according to Article 6 of the administrative measures for clinical application of antineoplastic drugs (Trial) (hereinafter referred to as the administrative measures) formulated by the organization on December 22, 2020, the classification standard of restricted use level of drugs is changed to: new anti-tumor drugs with high toxicity and side effects, strict indications, many contraindications, short marketing time and little experience in drug use, which are expensive Anti tumor drugs with heavy economic burden.

In accordance with the classification standard of the administrative measures for clinical application of antineoplastic drugs (Trial), the guiding opinions of Guangdong Pharmaceutical Association include the anti-tumor drugs with high toxic and side effects, less than three years of domestic marketing (drugs listed after January 1, 2019), and the average monthly cost of 15 000 yuan or more, and specifically mentions the immunosuppressants, immunosuppressants, and anti-tumor drugs with a monthly average cost of more than 15000 yuan In principle, cellular immunotherapy (car-t, NK), monoclonal antibodies (CD20, CD30, BCMA, bite, CD33, CD52, etc.) and tumor vaccines were included in the restricted use level management in principle.

On this list, the 21st century economic report reporter also called the Guangdong Provincial Pharmaceutical Association for further inquiry, saying that the list is only a reference directory, and has no administrative effect.

The guidance also made further relevant provisions on the prescription authority grant and the management of medical institutions, and implemented the restriction management of anti-tumor drugs to the level of medical institutions. This includes the management of prescription right of doctors, the training and assessment of clinical application knowledge of anti-tumor drugs in medical institutions, and the supervision and management of the use of anti-tumor drugs in medical institutions. Among them, it is suggested that medical institutions should warn doctors who have been prescribed more than three times without justifiable reasons to limit their prescription rights; After the limitation of prescription right, the prescription right shall be cancelled if there are still two or more abnormal prescriptions without any justifiable reasons《 The specific circumstances of canceling the prescription right of doctors are also listed in the guiding opinions.

"In general, the starting point of the policy is to standardize the use of drugs, but we also hope to have reasonable arrangements under the premise of ensuring the accessibility of patients." An industry source told the 21st century economic report, "for example, doctors above a certain level can prescribe treatment plans. Some of us are worried about whether patients who are difficult to register or even unable to register can get the required treatment drugs in time."

In these criteria, the upper limit of 15000 yuan per month is directly set from the economic point of view, but is there a one size fits all situation in the limitation of monthly average cost?

In addition, we are cautious about the new drugs that have not been on the market for less than three years and directly put them into the restricted use level. Is this contrary to the national policy of encouraging innovative research and development in the field of anti-tumor in recent years?

For PD-1, cell therapy and other popular products that have been included or will be included in the medical insurance, it has aroused widespread concern in the industry. The use of drugs listed in the medical insurance list is still restricted. Will this inhibit the enthusiasm of enterprises for innovation?

"With too many patients, it is unlikely that all of them will go to the expert number. Therefore, even if it is a product with better curative effect and cheaper price, patients may not be able to use it. In fact, it is different from the national policy of encouraging innovative drugs, accelerating access and improving patients' accessibility." The industry said.

How to balance the conflict?

According to the 21st century economic report, there are 21 Medicare class a drugs and 50 medical insurance class B drugs in the restricted use list issued by Guangdong Pharmaceutical Association, accounting for the majority of 78 drugs recommended to be included in the restricted use level.

On July 30, the medical insurance bureau also announced the adjustment of the national medical insurance drug list in 2021, which has passed the preliminary examination of the drug list. All four domestic PD-1 products approved for new indications were included in the preliminary review list, including 2 new indications for junshitreprizumab injection, 3 new indications for baijitirelizumab injection, 3 new indications for Xinda xindilimab injection, and 2 new indications for Hengrui injection of carrizumab. AstraZeneca's dovalizumab (PD-L1), Bristol Myers Squibb's navulizumab, mosartan's pabolizumab, and China's first approved car-t product, foscarnet's azirensai injection, were also included in the preliminary review list.

In view of the fact that some drugs which are more expensive in the market have passed the formal examination and whether they can finally enter the list, the state medical insurance bureau also made a special explanation in the interpretation of the publicity work: "some of the more expensive drugs have passed the preliminary formal examination, which only means that after the preliminary examination, the drugs meet the application conditions and are qualified to enter the next adjustment link. Whether such drugs can be included in the national medical insurance drug list will be subject to strict evaluation, including economic aspects. Exclusive drugs can only be included in the list after price negotiation

"It remains to be seen whether it can be negotiated, but it also shows that the national health insurance still holds a relatively open idea for this innovative drug." On the evening of July 31, at the meeting of "chief night & quanzheng discussion" of 2021 (38th) national pharmaceutical industry information annual meeting, Chen Yiling, chief analyst of Guoxin Securities Co., Ltd., said that car-t therapy had passed the above preliminary form review list.

However, at the same time, the PD-1 / PD-L1 anti-tumor drugs mentioned above are included in the restricted use level reference list together with Roche's atilizumab (PD-L1). On the one hand, it is the efforts of medical insurance to improve the accessibility of drugs, and the other is to maintain fairness. How to balance the conflict between the new anti-tumor drugs with short marketing time and less experience, and the high price and heavy economic burden of anti-tumor drugs?

Policy changes affect the market

In recent years, the use of anti-tumor drugs in emerging markets including China has been increasing.

According to iqvia's review and Trend Outlook of global drugs in 2020 released in May 2021, from 2009 to 2019, due to the introduction of new therapies in the global emerging markets, the drug consumption in the field of cancer has increased significantly: the compound annual growth rate of tumor drug consumption is 32%, and the increasing accessibility of innovative drugs is the main driving force of the increase in consumption.

In recent years, China has been encouraging the development of innovative drugs in policy. In 2015, the State Council's opinions on reforming the review and approval system for pharmaceutical and medical devices and the 2017 opinions on deepening the reform of the review and approval system and encouraging innovation of pharmaceutical and medical devices have defined the top-level design for the development of innovative drugs. Since 2017, China has been accelerating the review and approval of innovative drugs every year. Since 2018, the procurement of generic drugs and the normalization of medical insurance negotiation of innovative drugs have been normalized, which supports pharmaceutical enterprises' innovation by accelerating the entry of innovative drugs into medical insurance and providing more financial support for innovative drugs through medical insurance transfer.

As the main direction in the field of innovative drugs, many anti-tumor drug manufacturers benefit from these policies, and the heat of related research is on the rise, so that a large number of anti-tumor drugs are put into clinical use. The survival time of cancer patients has been prolonged by the new treatment methods, and the malignant tumor has become a chronic disease. However, many problems also appear along with the development of the industry. The repeated research and development of popular targets in PD-1 and car-t fields, and a large number of "pseudo innovation" phenomena appear, resulting in a large number of repeated trials and waste of resources, and the clinical value has not been improved.

Therefore, while the State Food and Drug Administration issued policies to crack down on "pseudo innovation", the National Health Commission has constantly issued policies to regulate the clinical practical management of anti-tumor drugs to rectify the disorder in the process of drug use.

In the list released by Guangdong Province, there are some drugs with high sales volume and wide application in China, involving pharmaceutical enterprises, such as Roche, Novartis, AstraZeneca, Pfizer, Johnson & Johnson, etc., as well as domestic well-known innovative pharmaceutical enterprises such as Baiji Shenzhou, Qilu pharmaceutical, Xinda and Zhengda Tianqing.

Investors are worried that with the continuous promotion of similar policies across the country, the stock prices of innovative drugs will also be affected. Prior to that, CDE issued the "notice on Soliciting Opinions on the guiding principles of clinical value oriented clinical research and development of anti-tumor drugs" on July 2, which triggered a sharp fall in the stock prices of biopharmaceuticals and CXO related listed companies.

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