Who is the fastest among 39 heavy imported drugs such as BI, Novartis and Johnson & Johnson？

The large-scale China market has been opened, and the giants of multinational pharmaceutical companies are deploying. China’s innovative drug market has become a battleground for enterprises.

New drugs brought about by the priority review and approval and the accelerated registration of imported drugs have been listed in China, reaching the first small climax in 2017.

In 2017, the number of imported innovative drugs registered in China for the first time reached 39, including 34 chemical drugs and 5 biological drugs. Most of them were approved through the priority review process, and the fastest one took only five months from CDE acceptance to approval.

Moreover, as of the end of January 2018, there are still 20 imported innovative drugs in the review and approval queue, most of which have been included in the priority review and approval. It is expected to be approved in 2018~2019.

From the indication point of view, the treatment fields of these products are all over the popular treatment fields such as tumor, hypertension, diabetes, autoimmune diseases, hepatitis C, pulmonary hypertension, etc. Many products are direct competitors, and most of them are the first heavyweight varieties of the same type in the world. This not only greatly enriches the treatment options of patients, but also forms a competitive mechanism in price and expands the accessibility of drugs.

The huge China market has been opened, and the giants of multinational pharmaceutical companies are in the process of deployment. China’s innovative drug market has become a battleground for enterprises. With the deepening of the reform of drug evaluation system and China’s increasing participation in international multi-center clinical research, the "China time difference" of global new drugs is getting shorter and shorter.

BI, Novartis and Johnson & Johnson are in the first echelon according to the number of products approved by enterprises.

one

China becomes the largest emerging market of BI.

China has become the largest emerging market of BI, with a large number of new drugs that were previously stuck in the approval process being approved one after another.

In 2017, a total of five innovative chemical drugs of BI were approved by CFDA, including two hypoglycemic drugs, namely, O-Tang Jing (Engleggin) and O-shuangning (Liggliptin/Metformin), one antihypertensive drug, Shuangjia (Telmisartan-Amlodipine), and two anticancer drugs, Nidanib (Wigardt) and Afatinib (Gitairui), for the treatment of non-small cell lung cancer.

Among them, the listing of afatinib is of nodal significance. It is the first imported new drug whose "listing application" has been given priority review, and it is also the first imported new drug approved for listing by CFDA with the qualification of "priority review". As the first EGFR-TKI in China, its curative effect is significantly better than that of the first generation. Its listing indicates that the speed of overseas new drugs entering China will be greatly accelerated.

Afatinib was approved by more than 70 countries to treat EGFR mutation positive non-small cell lung cancer before it was approved in China, and it has become the first choice of EGFR targeted drugs in many areas. It was first approved in July 2013 in the United States, and was approved in China after an interval of three years and eight months. Compared with the average interval of five years when international new drugs are approved in China, it is two years ahead of schedule.

In 2016, the global sales of SGLT-2 inhibitor, a new oral hypoglycemic drug, was US$ 4.58 billion, but this kind of drug has just started in China. Dapagliflozin, AstraZeneca’s new diabetes drug approved in March 2017, is the first SGLT-2 inhibitor listed in China. As the second SGLT-2 inhibitor listed in China, Engleggin was listed later than Dapagliflozin. At present, the two products are direct competitors. Among local enterprises, Hengrui, Dongyang Guangyao and Xuanzhu Medicine have already started clinical trials, and Hengrui’s Henggelijing started the Phase III clinical trial in June last year, which lasted for 52 weeks.

Nidanib ethanesulfonate soft capsules for the treatment of specific pulmonary fibrosis (IPF) were accepted by CDE on April 17th, 2017, included in the priority review on June 6th and approved on September 22nd. A total of five months, it can be described as rapid.

The global IPF market will reach US$ 3.2 billion in 2025, and the global sales of Nidanib in the first half of 2017 is 429 million euros (RMB 3.36 billion), which is one of the best performing drugs in that year. There are about 500,000 IPF patients in China, and the number of cases is increasing. Before the approval of Nidanib, the only domestic product to treat IPF was pirfenidone from Roche. At present, both products are expensive. It is worth noting that the new drug Ifinidone for IPF developed by Guangdong Zhongsheng Pharmaceutical Co., Ltd. has been approved for clinical use by CDE.

Undoubtedly, the approval of these products in China will boost the strong growth of BI’s performance in China in the next few years. According to the data, as of January, 2018, BI has two innovative pharmaceutical products, Audat Luo and Tiotropium Bromide, which are under review and approval, and both are in the priority review process.

Both drugs are COPD (chronic obstructive pulmonary disease) drugs. The global and domestic COPD markets are expanding, but there has been a lack of heavy products. Tiotropium bromide has always been the best-selling product of BI, and it is predicted by EvaluatePharma that it is the only drug that may enter the "Top 50 Best-selling Drugs List in 2020" in the field of COPD.

At the same time, in 2018, BI will also develop biopharmaceuticals in China.

In May 2017, BI China Bio-pharmaceutical Base was officially launched in Shanghai Zhangjiang Hi-tech Park, which is the fourth bio-pharmaceutical base of BI after German, Austrian and American, demonstrating its determination to use this base as a "bridge" and quickly enter the bio-pharmaceutical market in China. In the beginning of 2018, BI signed a commercial supply agreement with Baekje Shenzhou on the latter’s research on the PD-1 antibody tislelizumab, which was produced in the biopharmaceutical production base as an exploration of the drug marketing license holder system.

Prior to this, BI has promoted 27 biopharmaceutical products to the global market, and the establishment of the fourth biopharmaceutical base in China will also accelerate the listing of its biopharmaceutical products in China.

2

Novartis: Innovation Drives Growth

Novartis has always been defined as a pharmaceutical company driven by innovation. At present, the impact of the expiration of Gleevec’s patent is being offset by the gradual increase of innovative pharmaceutical products listed later. According to the financial report released by Novartis Group, the net income of Novartis increased by 2% in 2017, among which products such as Cosentyx and Noxintuo grew strongly.

For Novartis, listing more innovative drugs in China is an important link for it to increase the innovative market in China. As early as 10 years ago, Novartis set up a biomedical research center in China, which is also one of its three R&D centers in the world. In the China market, in 2017, Novartis had five products, namely indane Dutrow/glycopyrrolate (Jierun) for treating COPD, shakubit-valsartan (Noxintuo), rucotinib (Jiekewei) and pezotinib (Vequantel), and also included a biological drug, namely omazumab (Zhuole) for treating asthma.

Among them, Shakuibi Trivalsartan is a breakthrough and innovative drug in the treatment of chronic heart failure in the world in recent 20 years. According to reports, Noxintuo has been off the assembly line at Novartis Changping factory at the end of 2017 and officially entered the market.

Lucotinib is currently the only targeted drug approved for the treatment of myelofibrosis in the world. In 2016, Jiekewei’s global sales reached US$ 853 million. Thanks to the expansion of the global bone marrow fibrosis market, Jiekewei also maintained a double-digit growth in 2017H1. At the launch conference of Jiekewei, Novartis said that china charity federation Jiekewei patient assistance project will also be launched during the year to ensure standardized treatment for patients.

Omazumab is the first monoclonal antibody drug in the world and the only one in China to treat asthma. It was first marketed in Australia in 2002, and has been approved for marketing in more than 90 countries around the world, and its indications are gradually expanding. In the past five years, its global sales have steadily increased. In 2016, its global sales reached 2.356 billion US dollars, making it a well-deserved heavy biopharmaceutical.

China is one of the countries with the highest mortality rate of asthma, and the prevalence rate is increasing gradually. There are many kinds of asthma treatments listed in China, but most drugs still can’t control the symptoms of patients. As the first targeted drug, omazumab will open a new chapter in the treatment of allergic asthma. If the price is reasonable, it will be rapidly released in China market. However, Novartis is also facing competitors. Among local enterprises, omazumab biological analogues from Zhangjiang Biological and other enterprises have entered clinical phase III.

Sertinib, the second-generation ALK inhibitor under review and approval, was approved by FDA as the first-line therapy for ALK+ non-small cell lung cancer in 2017. It is expected to join the priority review and approval queue in the future.

three

Johnson & Johnson: Two Heavy Biological Drugs Entering China

In 2017, Johnson & Johnson listed the leukemia drug Ibotinib (Yike), the hepatitis C drug cimetivir (Olesen) and the new type 2 diabetes drug Carglinide (Yikean) in China.

With a strong research and development pipeline for autoimmune diseases, Johnson & Johnson has also listed two biopharmaceuticals in China, namely Gorimumab for treating ankylosing spondylitis and Usinotuzumab for treating psoriasis. It is also full of harvest.

Golimumab is the first approved anti-rheumatic TNF preparation injected subcutaneously once a month in China, and it is also one of the top ten anti-rheumatic drugs in the world. In the global market, the global sales of golimumab have been rising all the way. In 2016, it sold $1.745 billion, ranking 36th in the top-selling drug top50 list in 2016.

The indication of Gorimumab approved in China is ankylosing spondylitis, but in the world, four indications have been approved. With more indications approved in China, it will compete for market share with imported TNF inhibitors such as Hummel, Leike and Enli, and domestic TNF inhibitors such as Yisaipu, Qiangke and Anbainuo.

The current market of TNF inhibitors in China is about 1.5 billion yuan, and the potential market exceeds 10 billion yuan. Domestic Yisaipu occupies more than 60% market share with price advantage. In the new national medical insurance catalogue in 2017, the recombinant human tumor necrosis factor receptor-antibody fusion protein was included in the national medical insurance category B for the first time, which will expand the TNF inhibitor market as a whole and help to increase the volume of golimumab, but the pricing problem still needs to be considered.

Usinotuzumab is a classic standard drug for psoriasis, benefiting from the overall rapid expansion of the autoimmune disease drug market, which rose by 24% in 2017 and exceeded $4 billion for the first time.

four

Multinational pharmaceutical giants are leading the way.

In 2017, the number of new drug approvals in the second echelon was AstraZeneca (3), AbbVie (2), BMS(2) and Bayer (2).

Amritsar from AstraZeneca was approved for the treatment of type 2 diabetes, and it was a competitor with Ou Shuangning from BI. The listing of Teresa, a third-generation targeted drug for non-small cell lung cancer, created the fastest record of less than one month from approval to marketing, and in just a few months, it had already sold $23 million in China, and soon after approval, it was included in the scope of serious illness medical insurance in Zhejiang Province.

Abvir is a joint listing of two antiviral treatment schemes for hepatitis C, Obipali tablets and Dasebvir sodium tablets, which is called "3D scheme". It is used to treat adult chronic hepatitis C with genotype 1, and the course of treatment can be as short as 12 weeks. It took only 6.5 months from listing to approval, and 2 months from approval to listing. At present, patients in Shanghai, Beijing and Zhejiang have enjoyed the drug. It is reported that another heavy hepatitis C pan-gene product of AbbVie has been approved for listing in the United States, the European Union and Japan, and the course of treatment has been shortened to 8 weeks. In the future, AbbVie will promote the listing of this innovative drug in China.

In September 2017, Gilead’s hepatitis C drug sofebuvir was also approved for listing by CFDA. So far, in the field of direct oral anti-hepatitis C virus (DAA) treatment, there has been a situation of direct competition among four multinational pharmaceutical companies, namely cimetivir from Johnson & Johnson, daratavir+Ashurivir from BMS, Obpari+Dasebuvir Sodium Tablets from Abbey and Sofibuvir from Gilead. In local enterprises, Geli’s Dannuo Ruiwei is also listed soon, and a number of enterprises are eyeing it. It can be seen that the competition in this field is fierce.

Among the 20 imported innovative drugs to be approved in the future, navuzumab from BMS is worthy of attention. This is the first PD-1/PD-L1 monoclonal antibody approved for marketing in the world, and the first PD-1/PD-L1 monoclonal antibody applied in China when it was submitted. It has been approved for 9 indications in the United States.

Levatinib from Weicai Company has been approved for the treatment of refractory thyroid cancer in more than 50 countries or regions, and it has been approved for the second-line treatment of renal cell carcinoma in more than 40 countries in combination with everolimus. The indication for this application in China is hepatocellular carcinoma.

There is also Amgen’s world’s first CGRP monoclonal antibody Eloizumab injection, which is used to prevent migraine. Some analysts predict that it can achieve annual sales of up to $12.5 billion worldwide. Olapali from AstraZeneca is the first PARP inhibitor listed in the world, and Lydiparvid/Sorobupvir from Gilead is a daily compound single-chip cocktail therapy … …

Part of the data in this paper comes from GBI Health report "Summary of New Drug Evaluation in 2017" by Deng Gaifang.