Commercial Competition Of Domestic PD-1 Medical Insurance In The New Era

On March 1, 2021, the new version of medical insurance drug list was officially opened, and domestic PD-1 products ushered in a new era of medical insurance.

After Sinda biological PD-1 drug sindilimab entered the medical insurance after negotiation and reduced the price by 63.73% in 2019, all four domestic PD-1 products participating in the 2020 medical insurance negotiation were selected. After the super buyer of the National Health Insurance Bureau's "price cut", the domestic cost of PD-1 has entered the era of "10000 yuan" paid by patients themselves.

Since PD-1 / L1 has become the innovation track selected by local pharmaceutical enterprises, the competition of domestic PD-1 has become increasingly fierce from the target of R & D phase, the selection of indications, the speed of clinical trials and review and approval, to the listing, price, admission to hospital, medical insurance and sales team building in the commercialization stage.

This time, the competition of several domestic PD-1 almost returned to the same starting line after the unified big price reduction to enter the medical insurance in exchange for "basic sales". The management of many enterprises have said that the competition focus of PD-1 in the future is production capacity, indications, and overseas market.

Even if the competition situation is getting tighter, the applicable tumor species and combination market of PD-1 / L1 still looks promising. According to the statistics of evaluate vantage, oncology drugs will continue to be the main driving force of revenue growth in the pharmaceutical industry in 2021. Of the 10 most popular new products, six are used to treat various cancers, and three of them are anti PD-1 (L1) antibodies.

With the opening of a new era of competition, domestic PD-1 enterprises are actively choosing more commercial channels and expanding paths for their own products through cooperation, authorization or self construction.

"Sino foreign cooperation" accelerated

On February 28, AstraZeneca and Junshi bio jointly announced that they had reached a commercial strategic cooperation on the PD-1 drug treprilimab. Junshi bio will grant the right to promote the non core market of AstraZeneca in mainland China, as well as the national exclusive promotion right for urothelial cancer indications that have been approved for marketing. At present, the indications for urothelial cancer have not been approved in China.

Treprilimab is the first PD-1 drug approved for marketing among local pharmaceutical companies. Currently, it has been approved for two indications in the field of melanoma and nasopharyngeal carcinoma. The first indication approved is unresectable or metastatic melanoma which has failed to receive systemic treatment in the past. In December 2020, it was included in the new medical insurance list through the negotiation of national health insurance. The price of 80mg (2ml) is 906.08 yuan / piece, the annual treatment cost is 70700 yuan, the decrease rate is more than 70%, the reimbursement rate of medical insurance is 50% - 80%, and the self payment of patients is about 14100-35300 yuan.

According to the performance express released by Junshi on February 27, the revenue in 2020 will be 1.594 billion yuan, with a year-on-year increase of 105.77%, which is mainly caused by the increase of treprilimab sales revenue and the new technology licensing revenue, which can be basically regarded as the revenue of PD-1.

Junshi said that the cooperation is a supplement and expansion of the commercialization of triprilimab. Due to the limitation of indications in medical insurance, Junshi biological will open up more commercial channels for the follow-up indications of PD-1 after medical insurance negotiation.

AstraZeneca has its own PD-L1 inhibitor, imfinzi dovalizumab. At the end of 2019, the State Drug Administration approved imfinzi for the treatment of unresectable, stage III non-small cell lung cancer without progression after concurrent chemoradiotherapy.

For AstraZeneca, which owns "I drug", it can use the original channel to have more say in the PD-1 / L1 market competition. As a "most localized" multinational pharmaceutical company, AstraZeneca has a strong sales team, sales network and commercial operation experience in the county medical market. After the price reduction of PD-1, it has more possibility of promotion in the county market.

AstraZeneca told the 21st century economic report that at present, the two products of imfinzi and treprilimab have been approved with no overlapping indications, and the two sides will carry out corresponding work according to their respective R & D plans.

Several other local PD-1 enterprises are also expanding foreign cooperation. On January 12, Baiji Shenzhou announced that it had reached a cooperation with Novartis to develop and commercialize anti PD-1 antibody tirelizumab. Novartis will jointly develop and commercialize tirelizumab in North America, Japan, the European Union and six other European countries. Baiji Shenzhou will receive an advance payment of US $650 million and be eligible for a potential registration and sales milestone payment of up to $1.55 billion, as well as products Sales royalties.

This is also the largest domestic drug authorization cooperation project with the highest down payment so far, with a total transaction amount of more than 2.2 billion US dollars, setting a record for the current domestic single drug authorization transaction amount.

In addition, the first year's sales results of tirizumab have also been released: on February 26, Baiji Shenzhou announced the full year financial performance of 2020. Among them, PD-1 tiralizumab was sold for 163.36 million US dollars in the first year, about 1.055 billion yuan. After entering the medical insurance system, the new price of tiririzumab before reimbursement was as low as 2180 yuan / piece (100mg), the price dropped by 80%, and the annual treatment cost was less than 75000 yuan.

The PD-1 of Cinda bio has been following the route of "Sino foreign cooperation" since its birth: sindilimab is a drug jointly cooperated by Cinda biopharmaceuticals and Lilly pharmaceutical in China. In March 2015, the two sides reached a cooperation in the development of biotechnology drugs, which is one of the largest cooperation between Chinese Biopharmaceutical Enterprises and multinational pharmaceutical enterprises. In August 2020, the two sides expanded their cooperation, and Cinda granted the exclusive license of Lixin dilimab outside China to North America, Europe and other regions. According to the latest performance disclosure, the revenue of sindilimab will exceed 2.2 billion yuan in 2020.

In addition, the carrilizumab of Hengrui pharmaceutical entered the medical insurance with a decrease rate of 85.21%, 2928 yuan / piece (200mg), and all four indications were improved. With Hengrui's sales capacity, the subsequent competitiveness of its PD-1 is still strong.

New battlefield of competition

After entering the medical insurance system, the development of production capacity, indications and overseas market has become the key to the next stop.

Wu Xiaobin, general manager and President of Baiji Shenzhou China region, said in an interview with 21st century economic report that the follow-up competition of PD-1 is not only the indication but also the competition of production capacity. "In the coming months or years, the main problem of PD-1 is capacity. Because PD-1 is a macromolecule and an antibody, its production is quite complicated. "

According to the report on the healthy development of China's biological antibody medicine industry, China's antibody drug industry has insufficient process experience, small reactors and low protein expression; generally speaking, the overall production capacity of breast-feeding cells is relatively small and relatively scattered. By the end of 2019, the total production capacity of breast-feeding cells related to antibody drugs in China was about 310000 liters, and the production capacity of China's major antibody drug enterprises was also high It is very difficult to compete with the production capacity of antibody drugs of multinational companies.

In terms of production capacity, Xinda biological is operating five sets of 1000 liter bioreactors, and the total capacity will be increased to 23000 liters after expansion. Junshi bio has two production bases in Suzhou Wujiang and Shanghai Lingang, with a total fermentation capacity of 33000 liters. Hengrui pharmaceutical has a production capacity of 26500 liters and an expanded capacity of 19440 liters. The current production capacity of Baiji Shenzhou is 24000 liters, and the capacity under construction is 40000 liters.

For future market considerations, Wang Xiaodong, founder of Baiji Shenzhou and chairman of the Scientific Advisory Committee, previously said, "PD-1 is a broad-spectrum anti-cancer drug. Many high-risk cancers in China, such as gastric cancer, esophageal cancer, nasopharyngeal carcinoma and liver cancer, need PD-1 in some patients. There are more than 4 million new cancer patients in China every year, and we think that nearly 2 million people can benefit from PD-1

For this reason, each family is developing different indications. At present, Hengrui PD-1 is the most approved indication, which covers lymphatic cancer, liver cancer, lung cancer and esophageal squamous cell carcinoma. On February 3, Cinda and Lilly announced that the second indication of cindilimab was approved: combination of pemetrexed and platinum chemotherapy for the first-line treatment of non-small-cell lung cancer. In January 2021, tiririzumab combined with chemotherapy for the treatment of first-line advanced squamous cell carcinoma and non-small cell lung cancer (NSCLC) patients was also approved in China.

To "dig for gold" in overseas market is also one of the commercialization paths that PD-1 enterprises choose. Under the pressure of medical insurance fee control, it is more important to win the overseas market.

This year, Baiji Shenzhou will submit the first listing application of tiralizumab in overseas markets, further opening the pace of overseas commercialization. In addition to 3 marketed indications and 2 declared indications, a number of monotherapy and combination trials are being carried out.

Chen Chen, an analyst in the pharmaceutical industry of UBS Securities, told the 21st century economic report that "although China's medical demand is huge, the threshold for controlling medical insurance fees is always there, so the domestic market is far from enough, and there is a lot of room for foreign markets to be explored. If we can eat the overseas market, it is really very good for domestic enterprises. But China's pharmaceutical enterprises, especially R & D enterprises, have a very weak sales capacity overseas. If it can be recognized by a very strong overseas sales team, it is very good to sell domestic drugs overseas, which can increase a lot of profit space for domestic enterprises. "

On February 1, 2021, Junshi bio announced its cooperation with coherus Biosciences on the development and commercialization of triprilimab in the United States and Canada. Junshi bio will receive a down payment of up to US $1.11 billion, optional project implementation fee and milestone payment, which is also an important part of its expansion of global commercial network. Up to now, triprilimab has been awarded one breakthrough therapy accreditation, one fast track accreditation and three orphan drug qualification accreditation by FDA in the fields of mucosal melanoma, nasopharyngeal carcinoma and soft tissue sarcoma. It plans to submit an application for listing in the United States in the near future.