Accelerated review and approval of imported drugs poses challenges, and local pharmaceutical companies should not ignore these five points!

Shortly before the news on June 13th, the State Food and Drug Administration and the Health and Health Commission jointly issued the "Announcement on Optimizing the Relevant Issues Concerning the Examination and Approval of Drug Registration," which is seriously life-threatening and has no effective treatment for diseases that have been listed overseas. As well as rare disease drugs, if the applicant for imported drug registration believes that there is no ethnic difference, it can submit the clinical trial data obtained overseas to directly apply for registration of the drug. This also means that the speed of listing of some imported “life-saving drugs” in China will accelerate. On the one hand, it is good for patients. On the other hand, local enterprises will also face a new competitive environment. How to face such a trend, the author shares some views here.

1. Strengthen the tracking of basic research

We know that the development of original new drugs is often based on a strong basic research in the medical sciences. The participation of local pharmaceutical companies or basic research in many research institutions, despite significant progress in recent years, still lags behind the US, Europe and Japan in many fields. It is an indisputable fact that developed countries and regions such as Australia need innovative pharmaceutical R&D personnel to closely track the progress of basic medical research in developed countries.

For example, anti-cancer drugs are the first to bear the brunt of the examination and approval of imported drugs . In the past, local research and development adopted Me too or Me better ideas. However, after the original foreign innovative drugs speed up the listing, this kind of thinking must be adjusted. If local companies can start early in research and development according to the mechanism of tumor occurrence, development and recurrence, it is possible to take advantage of some of the control measures, and then seize the opportunities in the market, so that products have better input and output. ratio.

2 , update the research and development of anti-tumor drugs

Angiogenesis is recognized as an important step in the growth and progression of many tumor types. Anti-angiogenic therapy has been an effective way of treating cancer for the past 15 years. The FDA has approved several vascular endothelial growth factor/receptor (VEGF/R) inhibitors for various solid tumors. Although improvements in progression-free survival (PFS) have been observed, the impact of anti-angiogenic therapy on overall survival (OS) is limited. There is evidence that changes in tumor microenvironment (TME) play a key role in this adaptation. Role - By targeting TME, it has become a new strategy to overcome tumor anti-angiogenesis. Among them, solid tumor hypoxia is an important factor in drug resistance, radiotherapy resistance and anti-drug therapy.

1. Anti-hypoxia-related studies suggest that tumor hypoxia may accelerate the progression of cancer and make it more tolerant to treatment. Like many other tumors, prostate cancer is usually hypoxic. Casodex can improve prostate oxygen content and become a successful case of anti-tumor adjuvant therapy.

2. Antiplatelet anticoagulation Some coagulation factors have been shown to be one of the causes of tumor cell metastasis. Many patients with advanced malignant tumors die from diffuse intravascular coagulation.

3. To exert the Chinese medicine specialty Chinese medicine has a history of treating blood circulation and removing blood stasis, and has been confirmed in modern anti-tumor treatment. The mechanism has anticoagulant and antithrombotic effects as well as anti-hypoxia. Under the support of the national policy of supporting Chinese medicine, I believe that the theory and practice of anti-tumor of traditional Chinese medicine can continue to flourish and find a better drug combination.

3 , old drugs play a new mechanism

After the new indications new drugs enter the market, the key to ensuring market exclusivity lies in the design and operation of new indication patents, as well as the analysis and control of channels.

Recently, some old drugs have solved the urgent needs of the clinic. For example, in the absence of a rapid and effective treatment regimen, the detrimental effects of depression are increasing, and currently available drugs are only effective in about two-thirds of patients, highlighting the fact that treatment of depression is a major unmet clinical need.

Recently, there have been foreign reports that an old drug and its derivatives that have been used for many years have undoubtedly demonstrated extremely satisfactory results. This drug is ketamine. This is an anesthetic that has entered the national base drug list and has been on the market for many years. The study found that a single dose of ketamine produces a rapid (in a few hours) antidepressant response that lasts for about 1 week, and can be an inspiring effect even in patients considered to be resistant to treatment. Ketamine has also been shown to be effective in the treatment of suicidal ideation.

At present, pharmaceutical companies are striving to develop ketamine-like drugs with fewer side effects and drugs that work in other parts of the glutamate neurotransmitter system. In addition, targets for enhanced glutamate neurotransmission or synaptic function (or both) have been studied, and these targets are critical for rapid and sustained antidepressant effects of ketamine in rodent models.

The discovery of ketamine and its unique mechanism of action indicates a new era and has great prospects for the development of new, rapid and effective antidepressants.

4 , pay attention to the evaluation of pharmacoeconomics

The evaluation of pharmacoeconomics is related to the R&D, use and review and approval management departments. For new drugs developed by follow-up pharmaceutical companies with the same target and mechanism as the already listed but expensive drugs, if they can replace expensive imported drugs at a lower price in the future, they should be given market access, medical insurance, etc. Good offer. Of course, R&D institutions must avoid the patent protection of the original drug and avoid infringement.

5 , closely watch the large variety of patent protection

If a new drug has been listed abroad, it is developed by a multinational pharmaceutical company with certain strength, and its research and development stage has generally applied for a patent in China. In view of this, local pharmaceutical companies should analyze the characteristics of their patent structure on the premise of not causing infringement, and find the entry point for self-development.

Here, the industry can focus on Gilead's anti-hepatitis C drug Sovaldi (sofob). Sovaldi ranks more than 300 in global sales for infectious diseases (HIV, hepatitis, etc.). Currently, China has rejected a patent application for its prodrug, which is an inactive form of Sovaldi that will be transformed in the body. It is a chemically active compound. Tip here - similar prodrugs can be converted in vivo to the active ingredient, but research and development prodrug constitutes patent infringement, it should communicate with the patent agency people.

Due to the meticulous content of compound patents, the application of compound patents needs to be carefully analyzed, and the determination of infringement should be the focus. If the metabolite is a patented drug, there is also the possibility of infringement. In this case, the patent protection period should be avoided.

Another noteworthy drug is Apilimod, also known as STA-5326. Initially, Synta was developed as a drug for the treatment of rheumatoid arthritis, but recently, aplendide was used as an inhibitor of PIKFyve. It has been demonstrated that selective inhibition of IL-12/IL-23 transcription in immune cells is mediated by the combination of apicimod directly with phosphatidylinositol-3-phosphate 5-kinase (PIKfyve). At present, the mechanism has been studying the antiviral activity of aplendide, because studies have shown that it has significant activity against Ebola virus.

According to the data, it has been patented that the active metabolite of apicimod has been applied in the United States (mainly for cancer treatment), but whether an active metabolite can also be used to treat autoimmune diseases is worth further. the study. However, many large varieties do not pay attention to whether metabolites have higher activity when applying for compound patents. Therefore, they can also be used as an idea for research and development of innovative drugs, which can also reduce the risk of failure due to serious side effects.

In general, in response to the new situation of importing new drugs to speed up the review and approval of listing, as long as there are cooperation between R&D institutions, IP-related institutions, financial institutions and regulatory authorities in terms of policies and resource integration, it is also possible among local pharmaceutical companies. Promote the development of efficient new drugs. With the opportunity of China's participation in ICH, we can help more local pharmaceutical companies to go abroad and make greater progress.