Research and Development Status of Antidepressants from the Data of Application and Approval

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With the improvement of people's quality of life, everyone began to pay attention to their spiritual world. Depression is also slowly coming into view. According to the report on depression and other mental disorders released by the World Health Organization in February this year, the number of people suffering from depression in the world has reached 0.322 billion, accounting for about 4.4 per cent of the global population.

In terms of countries, the United States, Australia and Brazil account for more than 5.5 per cent of the population, Ukraine for more than 6 per cent and China for 4.2 per cent. According to the latest data from the National Bureau of Statistics, my country's population was 13746.21 million at the end of 2015, so it is conservatively estimated that there are more than 57.73404 million people suffering from depression in China.

With the gradual increase in the number of people with depression, the society calls for attention to depression and calls for the country to introduce corresponding protection policies one after another, and the quality and diversity of antidepressants are becoming higher and higher. So what is the current state of research and development of antidepressants in China? Let's take a look.

Domestic declaration

According to the drug registration and acceptance database, since 2000 (as of November 20, the same below), a total of 1565 registered acceptance items have been registered in 17 years (in terms of acceptance number, the same below). Among the registered types of antidepressants, there are 829 new drugs, accounting for 52.97 per cent (see Figure 1 for details). Among the new drugs, only hydroxpispirone hydrochloride declared by Zhejiang Huahai and ansufaxine hydrochloride declared by Shandong Green Leaf are 1.1 drugs, and hydroxpispirone hydrochloride has been listed as special approval and major special drugs.

Figure 1 Type of registration declaration for antidepressants (by acceptance number, unit: article)

In the classification of drugs, it is obvious that chemical drugs are the main force, with a total of 1517 declaration records, while traditional Chinese medicine is supplemented with only 41 declaration records (see Figure 2 for details).

Figure 2 Classification of drugs for registration of antidepressants (by acceptance number, unit: article)

From 2000 to 2017, the number of antidepressant registration applications fluctuated greatly, with peaks in 2005, 2006, 2014 and 2015. With the implementation of generic drug consistency evaluation and the introduction of a series of pharmaceutical innovation encouragement policies, the number of applications dropped sharply in 2016, reaching a new low this year. As of November 20, the number of applications in 2017 was only 36, and there was no shadow of new drug application this year.

Figure 3 Number of Antidepressant Registration Declarations from 2000 to 2017 (by Acceptance Number, Unit: Article)

Main varieties in domestic market

According to the varieties declared in the drug registration and acceptance database, we searched the domestic drug database and found that 24 varieties such as sertraline, venlafaxine, doxepin and citalopram have been approved at present (see fig. 4 for the top 10 varieties with approval). it can also be seen that there are not many antidepressant drugs on the market at present. From the perspective of drug dosage forms, tablets are mainly used, and injections and oral solutions are also available, but relatively few.

Figure 4 Top 10 varieties in the number of approved documents (in terms of approval number, unit: article)

From the perspective of being included in the medical insurance, among the above 10 varieties, except for bupropion, which is only included in the medical insurance in Hubei, Qinghai and Henan provinces, and is not included in the national medical insurance, the other 9 varieties are included in the medical insurance in more than 29 regions, and all are included in the national medical insurance. (See Figure 5 for details)

It is worth mentioning that doxepin hydrochloride tablets and clomipramine hydrochloride tablets are included in the varieties that must complete the consistency evaluation before 2018. According to the latest news from CFDA, there are 13 manufacturers of doxepin hydrochloride tablets with document numbers, 6 of which do not give up evaluation, 7 of which have given up and 5 of which have already carried out relevant work. There are 5 manufacturers of clomipramine hydrochloride tablets with document numbers, 3 of which do not give up evaluation, 2 of which give up and 2 of which have already carried out relevant work.

Figure 5 Statistics on the inclusion of drugs in medical insurance (by number of regions, unit: units)

In addition to the above 10 approved varieties, most of the other listed varieties are also included in the national and most regions, agomelatine, milapram for the 2017 national health insurance new varieties. (See Figure 6 for details)

Figure 6 Statistics on the inclusion of drugs in medical insurance (by number of regions, unit: units)

Four potential varieties

However, judging from the number of CDE acceptance, duloxetine, venlafaxine, sertraline and other varieties are more popular with enterprises. Compared with their approval documents, we can find that duloxetine, paroxetine, agomelatine and vortioxetine have a large number of acceptance documents, but the number of approval documents is small (see Figure 7 for details), which is definitely a high ground for major enterprises to compete in the future.

Figure 7 Comparison of the number of accepted documents and the number of approval documents (by acceptance/approval number, unit: article)

According to a research report by GF Securities, duloxetine is an antidepressant "blockbuster" drug listed by Lilly in 2004. Global sales exceeded US $5 billion in 2012, and the US patent expired on June 11, 2013. After the patent expired, a large number of generic drugs poured in. At present, there are 177 records of applying for the product in China.

However, according to the domestic drug database of Yao Zhi, only five duloxetine-related products are on the market, among which duloxetine hydrochloride enteric-coated tablets produced by Jiangsu Enhua, duloxetine hydrochloride enteric-coated tablets and duloxetine hydrochloride enteric-coated capsules produced by Shanghai Shangyao Zhongxi Pharmaceutical are included in Medicare Class B (see Figure 8 for details).

Figure 8

Paroxetine is the largest antidepressant drug in China, with annual sales exceeding 1 billion yuan. At the same time, it is also the only antidepressant among the 36 varieties that were successfully negotiated in the second round of medical insurance drugs in 2017. The newly added paroxetine hydrochloride enteric-coated sustained-release tablets imported by GlaxoSmithKline (China) Investment Co., Ltd. in this medical insurance negotiation. In addition, there are also 7 products from 4 companies in China that have been listed (see Figure 9 for details).

Figure 9

Compared with duloxetine and paroxetine, agomelatine and vortioxetine have fewer approvals. According to the domestic drug database of drug intelligence, only agomelatine tablets produced by Jiangsu hausen have been listed (see fig. 10 for details) and have been included in the 2017 edition of national medical insurance category B, as well as in the medical insurance category B by Gansu and Qinghai provinces. Up to now, no approval information for vortioxetine has been found. However, the imported vortioxetine hydrobromide tablets declared by Lingbei (Beijing) Medicine have been included in the 14th batch of drug registration applications for priority review procedures and are expected to be the first to be approved.