Four domestically produced PD-1s, ten new indications, and medical insurance negotiations are about to fall this year

The domestically produced PD-1 goes to sea for another journey

On September 13, BeiGene announced that the FDA has accepted a new drug application for its anti-PD-1 antibody drug tislelizumab injection for the treatment of unresectable, recurrent locally advanced or metastatic after systemic treatment Patients with esophageal squamous cell carcinoma

To a certain extent, the focus of competition among domestic PD-1 products has shifted from R&D and clinical to commercialization and internationalization

For Cinda, Junshi, Baiji, and Hengrui, which are in the first echelon in China, PD-1 is not only a competition for clinical research and development capabilities and expansion of indications, but also for medical insurance access and commercialization.

If Cinda’s rate of advanced medical insurance in 2019 puts Sintilizumab in a relatively leading position, then when all four domestic PD-1s enter medical insurance in 2020, they will once again stand on the same starting line

01 Negotiations on medical insurance are a must

In a poll on "PD-1/L1 What are you most concerned about?" initiated by the E-medicine manager a few days ago, nearly one-fifth of the readers are concerned about the upcoming 2022 medical insurance negotiations.

In June this year, the National Medical Insurance Administration released the "2021 National Medical Insurance Drug Catalogue Adjustment Work Plan" that "During the period from January 1, 2016 to June 30, 2021, with the approval of the State Drug Administration, the indication or There are major changes in the functions and indications and the company takes the initiative to declare and adjust the scope of payment for drugs

The performance of the four domestically-made PD-1 products approved before June 30 this year in the drug price negotiations this year is one of the focuses of the industry's continued attention

As the domestically produced PD-1 with the most medical insurance indications, Hengrui Medicine’s Karelizumab has been approved for six indications before the application deadline.

On June 10, Carrelizumab was approved for the first-line treatment of patients with locally recurring or metastatic nasopharyngeal carcinoma in combination with cisplatin and gemcitabine.

Baekje has the potential to catch up with Hengrui

As of the end of June, BeiGene tislelizumab has been approved for five indications

On June 23, NMPA approved tislelizumab for the first-line treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC)

As the first PD-1 product in China, Junshi Biotech's Teriplimumab has also been approved for two new indications

Sintilimab, the first to enter medical insurance and will face renewal negotiations this year, has three new indications

On June 28, NMPA approved the fourth indication of Sintilizumab injection, which can be combined with bevacizumab injection for the first-line treatment of unresectable or metastatic hepatocellular carcinoma that has not received systemic treatment before , Becoming the world's first PD-1 immune combination therapy approved for the first-line treatment of liver cancer patients

Judging from the approval date, there are many indications that step on the "deadline" to enter the medical insurance preliminary review list
.

However, the dispute over indications is just a microcosm of the current PD-1 internal volume.
.
.
Whether it can be included in medical insurance and at what price is a major problem facing the market access team of pharmaceutical companies
.

The fierce battle of PD-1's entry into medical insurance can be seen at a glance from the results of the 2020 medical insurance negotiations
.

In the 2020 medical insurance negotiations, Hengrui's Carrelizumab was included in the medical insurance payment for the four major indications of liver cancer, esophageal cancer, lung cancer, and lymphoma that year
.
The price paid in the medical insurance catalog shows that a single cost has fallen by 85%
.
BeiGene’s tislelizumab has two indications that are included in the medical insurance, including for the treatment of relapsed or refractory classic Hodgkin’s lymphoma and locally advanced or metastatic urothelial carcinoma, and the single-vessel reduction rate has also reached 80%
.
Junshi’s Teriplimumab is the only anti-PD-1 monoclonal antibody in the 2020 medical insurance catalog for the treatment of melanoma, and its price has also fallen by more than 70%
.
Prior to the above three PD-1s, Cinda BioSindilizumab reduced the price by nearly 70% to send the indication of relapsed or refractory classic Hodgkin's lymphoma after at least second-line chemotherapy to medical insurance.
, The actual price paid by the patient is about 29,000 yuan
.

Driven by the price cut in medical insurance negotiations, the current annual treatment cost of PD-1 has been as low as about 50,000 yuan, and the self-paid part of some patients with indications for some products is even less than 10,000 yuan
.

Previously, the National Medical Insurance Bureau announced that the negotiation period will be from September to October this year
.
It is presumed that the battle for the PD-1 medical insurance negotiation in 2021 will soon come .

02 Continuous "blood-making" of commercialization capabilities

According to Researchand Markets, the global PD-1/PD-L1 sales will grow at a compound annual growth rate of 23.
4% in the future, and it is expected to reach US$50 billion by 2025, and the domestic PD-1 monoclonal antibody market is conservatively estimated to be 30 billion yuan.

.

From the perspective of past sales, unlike Cinda, Junshi, and Baekje, Hengrui has strong sales capabilities as an established pharmaceutical company.
This is also reflected in the rapid development of Karelizumab in 2020.
On sales
.
Data before medical insurance negotiations in 2020 showed that at that time, Hengrui had more than 6,000 sales staff on the tumor line, among which nearly 2,000 were PD-1 full-time sales staff.
This huge number can even be several times the size of the sales team of innovative pharmaceutical companies
.
A huge sales force quickly opened up the market for Carrelizumab
.
It is also a drug outside the medical insurance catalog.
In 2020, the annual revenue of carrelizumab is about 4 billion yuan, while Junshi and Baiji only have 1.
6 billion and 1.
1 billion yuan; even Cinda, which has entered the medical insurance, 22 Sintilizumab with sales of 100 million yuan can only reach half of Henri Carrelizumab's sales
.

However, after the "price-for-volume" in which all members of the medical insurance negotiations reduced prices to enter the medical insurance in 2020, the competition of the domestic PD-1 was pulled back to the same starting line
.

Sales are one of the dimensions to measure the success of PD-1.
For the four major PD-1 pharmaceutical companies under the pressure of the same medical insurance control fee, only Cinda and Baekje have clearly announced their PD- 1 sales
.
The 2021 mid-year report shows that Cinda Bio's Sintilizumab and BeiGene's tislelizumab have sales of 1.
4 billion yuan and 800 million yuan, respectively
.

Junshi’s triprolizumab did not announce specific sales, but from the perspective of Junshi’s operating income increased by 267.
77% year-on-year to 2.
114 billion yuan, Junshi’s revenue mainly comes from triprolizumab and the new crown The strong performance of the neutralizing antibody Etesvizumab and the revenue growth of foreign licenses
.

In the past year, the domestic sales of Junshitraprilzumab have been remarkable
.
On the one hand, Junshi conducted commercial promotion through the establishment of a self-employed team.
On the other hand, in February 2021, Junshi chose to cooperate with AstraZeneca to grant its urinary drug triprolizumab to be subsequently approved for marketing in mainland China.
The exclusive right to promote the indications in the oncology field, and the exclusive right to promote all the approved indications in non-core urban areas
.
Obviously, Junshi and AstraZeneca have joined forces to further accelerate the commercialization of tereprizumab in China and expand the breadth and depth of coverage in urban hospitals and pharmacies at all levels
.
According to Junshi's 2021 semi-annual report, Teriplimumab has successfully covered approximately 3,000 hospitals and more than 1,500 specialty pharmacies across the country
.

After entering the medical insurance, Hengrui's karelizumab sales revenue increased month-on-month.
This also means that the sales of karelizumab in the first half of 2021 will not be good after the price of karelizumab has been greatly reduced
.
Obviously, the red line pressure of medical insurance control fees has a huge impact on pharmaceutical companies
.

The domestic market is limited, and it seems that pharmaceutical companies generally choose the path of commercialization to open up overseas markets
.
In fact, the four major domestic PD-1s have all gone to sea
.

In January 2021, BeiGene announced that its PD-1 monoclonal antibody was licensed to multinational giant Novartis for development and commercialization in multiple countries
.
Authorized region including the United States, Canada, Mexico and the European Union
.
BeiGene will receive an advance payment of $650 million from Novartis and will be eligible to receive a milestone payment of up to $1.
3 billion after reaching the milestone event
.
Regarding tislelizumab, BeiGene has previously stated that it is expected to cooperate with Novartis to submit a new drug marketing authorization application (BLA) for tislelizumab overseas, and submit Bezan combined chemotherapy to the CDE as a first-line treatment.
SBLA in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC)
.

While the FDA is accepting the new drug listing application (BLA) for tislelizumab injection, we can also see that the internationalization of BeiGene is accelerating
.

In addition to applying for BLA overseas and authorizing Novartis to develop and commercialize tislelizumab, BeiGene has a global team of more than 6,900 people and has begun to build a factory in the United States
.
In August of this year, BeiGene signed a purchase agreement to acquire an area of ​​approximately 170,000 square meters in the United States, of which more than 93,000 square meters are developable properties, including commercial biologics production, clinical research and development centers, and BeiGene Pharmacovigilance innovation base
.
The construction of the new base is expected to be completed in the middle of 2023.
The base is expected to produce biological agents in the initial stage, and may also produce small-molecule anti-cancer drugs
.
Regarding the future commercialization strategy, BeiGene President Wu Xiaobin previously stated that with the progress of internationalization, the income of overseas markets will gradually increase
.

Junshi's internationalization strategy is equally impressive
.
In February of this year, Junshi Biosciences announced that it has reached a cooperation with Coherus BioSciences on the development and commercialization of Teriplizumab in the United States and Canada.
Junshi Biosciences will receive a total of up to US$1.
11 billion in down payment and optional project execution fees.
And milestone payment, this is also an important part of Junshi's expansion of global commercialization network
.
As of now, teriprizumab has been granted 1 breakthrough therapy designation, 1 fast track designation and 3 orphan drug designations by the FDA in the fields of mucosal melanoma, nasopharyngeal carcinoma, and soft tissue sarcoma, and plans to be in the United States in the near future Submit a listing application
.

In contrast to Baekje's and Junshi’s overseas trips, Sintilimab is a biotechnology drug development cooperation reached between Cinda Biologics and Eli Lilly in March 2015, which already has “overseas ancestry”
.
In August 2020, Cinda and Eli Lilly jointly announced that the two parties would expand their strategic cooperation on Cinda Bio-PD-1.
Cinda granted Eli Lilly Sindilimab an exclusive license outside of China and promoted it to North America, Europe and Europe.
In other regions, Cinda Bio will receive a total of more than US$1 billion
.

It is worth noting that Sintilimab has also become China's first PD-1 whose marketing application has been officially accepted by the FDA
.
In May of this year, the listing application of Sintilimab combined with pemetrexed and platinum-based first-line treatment of non-squamous non-small cell lung cancer (NSCLC) was accepted by the FDA and entered the formal review stage
.

Earlier, the FDA granted Sintilizumab orphan drug designation in 2020 for the treatment of esophageal cancer and T-cell lymphoma, respectively
.
In the same year, Sintilimab also obtained the orphan drug designation granted by the European Medicines Agency (EMA), with the indication for peripheral T-cell lymphoma
.

Different from the above three innovative pharmaceutical companies, Hengrui's journey to the sea is very "independent"
.
In addition to April 2020, Hengrui Medicine announced an agreement with South Korea’s Crystal Genomics company to license carrelizumab to the latter for clinical development, registration and marketing in South Korea.
CG will pay Hengrui 1.
5 million In addition to the USD down payment and subsequent sales sharing, Hengrui hopes to lead the internationalization and overseas sales of its own products
.
Hengrui's 2021 semi-annual report shows that in the first half of the year, overseas R&D expenditures of 643 million yuan have been established in the United States and Europe, covering medical science, clinical operations, registration, pharmacology, statistics, quality management, pharmacovigilance and other departments including complete clinical research and development.
The team includes a total of 136 overseas R&D teams, including 95 from the US team and 31 from the European team
.

With the official launch of Kangfang Bio/CP Tianqing's Paimrizumab and Yuheng Bio's Sepalizumab, the domestic PD-1 fight has become increasingly fierce.
At present, there are Qilu Pharmaceutical, Kelun Pharmaceutical, Many companies such as Fuhong Hanlius are submitting listing applications or are in the process of accepting them
.

Incoming companies continue to increase and competition is becoming increasingly fierce.
Price cuts, deployment of large indications, expansion of combination drugs, and shifting their attention to overseas markets have all become the main competitive strategies of PD-1 companies
.
Who can stand out in this red sea and maintain lasting competitiveness will be the focus of the industry in the future
.