If you want to make a breakthrough in the PD-1 market under the trend of low prices, Fosun has only this set of "seven injuries"!

On April 22, Henlius's "Slulimumab injection (ie, recombinant anti-PD-1 humanized monoclonal antibody injection)" was used for unresectable or highly metastatically unresectable or highly metastatic antibody that failed standard treatments. The treatment of satellite-unstable solid tumors has been accepted by the National Medical Products Administration for drug registration and has been included in the list of products to be reviewed for priority review. It is expected to become the first anti-PD-1 monoclonal antibody for the treatment of MSI-H solid tumors in China. On the 23rd, the US FDA accelerated the approval of the PD-1 antibody dostarlimab (trade name Jemperli) acquired by GSK from Tesaro for the treatment of disease progression, mismatch repair defects (dMMR) recurrent or advanced in utero during or after platinum-containing chemotherapy Patients with membrane cancer. As a result, Jemperli has become the seventh PD-1 in the world, and the fifth domestically produced PD-1 is also at the end of its listing. But if GSK and Fosun want to catch up in the fiercely competitive PD-1 market, can it really be solved by a simple approval document? It is not just Fosun and GSK. It can be said that the entire innovative drug industry may face the same problems. Stimulated by the price cuts of medical insurance, it seems to be thriving on the bright side, but in fact many problems have gradually become prominent. More and more upstarts with innovative missions, and more and more traditional pharmaceutical companies entering the market, how to accept the benefits? They are all problems that need to be solved urgently. At least GSK and Fosun Pharma want to grab food from the other 4 PD-1s in China, and three factors must be clear.



Differentiation of indications will become the main direction of PD-1

Slulimumab is an indication for unresectable or metastatic highly microsatellite unstable (MSI-H) solid tumors that have failed standard treatments. The biggest feature of this indication is based on specific MSI-H tumor markers. Screening is carried out without distinguishing by cancer types, covering a wide range of patient groups. Unlike previous anti-tumor drugs that specify tumor types according to their sources, the "MSI studies" on immune checkpoint inhibitor treatments that have been carried out since 2015, the earliest phenotype was found in hereditary colorectal cancer, but later Studies have found that MSI-H tumors occur in multiple sites. The most common sites are the colorectal, endometrium, and stomach. It also occurs in other sites. It is said to be not limited to cancer treatments. On May 23, 2017, the FDA accelerated the approval of Pembrolizumab (Drug K) for the treatment of unresectable or metastatic MSI-H/dMMR solid tumors in adults and children who have progressed after previous treatment and have no satisfactory alternative treatment options. And treatment of unresectable or metastatic MSI-H or dMMR colorectal cancer that has progressed after treatment. Become the first anti-tumor therapy approved by the FDA that is not distinguished by tumor source but by biomarker. 

This is the basis for slulimumab's claim that its indications fully cover high-incidence cancers. At present, many of its studies have entered the key clinical phase 3, with 2 single-drug and 8 combination therapy clinical trials, actively using chemotherapy and owning VEGF , EGFR-targeted monoclonal antibodies and other treatment programs to carry out immune combination therapy, and implement differentiated clinical development based on the characteristics of cancer patients in China. On the other hand, although the industry has basically reached a consensus that all colorectal cancer patients should be screened for MSI status, the domestic biomarker differentiation of anti-tumor therapies is far from reaching the clinical landing, and most clinicians still do not understand the MSI status. The definition and the significance of the report are generally not clear about the specific method of MSI detection. The changes are related to the entire medical system, rather than simply talking. At the same time, if the drug is launched in China, it will undoubtedly become the target of many PD-1 producers, and it is still unclear whether it can be approved for MSI-H solid tumors of all diseases, and there is a high probability that it will be selective in high-incidence diseases. Approved (colorectal cancer, endometrial cancer, etc.).

Data source: Yaozhi data

In summary, Fosun’s slulimumab does have certain advantages compared with other domestic approved PD-1 products in terms of indications (other manufacturers have related layouts are not excluded), and the market space it faces may also be It is relatively larger. As for whether it can be widely used clinically in China, it will be verified by time.



To hurt the enemy first, hurt yourself first, under the trend of low prices, biting is the key

On March 1, the new version of the medical insurance catalog was officially implemented. So far, the four domestic PD-1s have basically been at the same starting line in terms of medical insurance access. With the subsequent product launches and the advancement of the medical insurance catalog, it is expected that the PD-1 pricing will continue to increase significantly. Decline. At the same time, due to the high repetition rate of PD-1 indications (especially non-small cell carcinoma, Hodgkin’s lymphoma, etc.), 4 PD-1 manufacturers are competing for the market, reducing market profit margins year by year (Xinda Biotech When the medical insurance agreement expires at the end of the year, it is estimated that the insured price will be reduced by one third on Hengrui's basis), and will face the market after the PD-1 of Fuhong Hanliu, Qilu Pharmaceutical, Kelun Pharmaceutical and other companies pass the review and enter the market. What kind of scene? In July 2020, the National Medical Insurance Administration issued the "Interim Measures for the Administration of Medications for Basic Medical Insurance", establishing a standardized mechanism for the access and withdrawal of the medical insurance catalog, and clearly proposed the establishment of a perfect dynamic adjustment mechanism, which is adjusted once a year in principle. It clearly pointed out that in the same treatment field, medicines whose prices or costs are obviously high and there is no reasonable reason will be removed from the medical insurance catalog. This means that once the latecomers in the PD-1 field are approved for listing, when they enter the medical insurance catalog, they will not only reduce profits due to the sharp price cuts, but also force the first movers such as Hengrui and Junshi Bio to take the next round of medical insurance. In the negotiations, follow up on the basis of latecomers to achieve the true meaning of "injury to the enemy and to hurt yourself first."

Too low prices will certainly allow companies to balance the huge amount of manpower and financial resources expended in previous research. This is undoubtedly worse for most innovative pharmaceutical companies that rely on financing to survive. In the current PD-1 stage, the low price trend is irreversible, and the layout companies can only bite the price and keep up with the rhythm of the team. Relatively large pharmaceutical companies such as Hengrui and Fosun will certainly rely on "low prices" to defeat their opponents. At the critical stage, whoever can't bite will be eliminated with a high probability.




Marketing capabilities that are not valued by innovative pharmaceutical companies have turned into the ultimate decisive factor

Today, the industry fundamentals agree that sales are basically proportional to the size of the sales team. What determines the final sales of PD-1 still depends on the company's own marketing capabilities. Public data shows that as of June 2020, Hengrui Pharmaceuticals has more than 6,000 sales personnel on the oncology line, of which nearly 2,000 are full-time sales personnel for PD-1. Successfully created the myth of Hengrui’s 4.5 billion Erica sales in 2020 (equivalent to the total sales of the other three PD-1s). At the same time, the sales gap created in this way has also attracted the attention of the other three companies. The recruitment announcements issued by BeiGene and Cinda Biological also fully show that the focus of recruitment is sinking from the first and second tier cities to the third and fourth tiers and even counties. . The commercialization team of Cinda Biotech is 1,100 people, Junshi Bio is 561 people, and BeiGene is not to be outdone. In two years, it has expanded from a few hundred people to more than 1,500 people by the end of 2020. The sales numbers of the three companies are all 2019. More than twice the year, and will certainly continue to increase in the future. Although Fuhong Henlius, Qilu Pharmaceutical, and Kelun Pharmaceutical have their own commercial teams, they may be prepared to spread the PD-1 sales channels before the products are launched!