Doctors and patients more recognized imports? Anti-cancer miracle drugs are racing for life and death, who is still irreplaceable

Everyone is equal in the face of cancer risk. However, in the choice of cancer drugs, the differences between people will be reflected immediately.

In the national medical insurance negotiations in 2021, the anti-cancer miracle drugs PD-1 and PD-L1 (immune checkpoint inhibitors) are still the focus of attention in the industry. Not surprisingly, the domestic four giants with 8 new indications were successfully included in the national medical insurance directory.

The three foreign-funded pharmaceutical companies shortlisted for the national medical insurance negotiations this time still did not enter in the end.

For such a "defeat" result, there are constantly voices of foreign pharmaceutical companies.

In fact, not entering medical insurance does not mean that imported PD-1 and PD-L1 will lose the Chinese market. On the contrary, due to the adherence to pricing strategies, foreign pharmaceutical companies may still have a very "moist" life.

The "volume" of the Chinese market may really be just an "inner volume".

Subject to global pricing

In 2014, Bristol-Myers Squibb's O drug "Opdivo" and Merck's K drug "Keytruda" were launched and achieved great success, setting off a global pharmaceutical company's research and development boom for "anti-cancer miracle drug" PD-1.

As a result, T-drug, I-drug, and B-drug came to the stage one after another – in the following three years, Roche's T drug "Tecentriq", AstraZeneca's I drug "Imfinzi", Pfizer B drug "Bavencio" were launched, and the global competition pattern of PD-1/PD-L1 drugs was initially formed.

Immunotherapy for large-scale cancers has been basically monopolized by the above five drugs for a long time.

O-Drug became the first PD-1 drug approved for marketing in China, thus ushering in a new era of cancer treatment in China.

As the country with the highest incidence of cancer in the world, China's domestic pharmaceutical companies are naturally not willing to lose the advantages of local combat.

After several years of fighting, Junshi Biology, Innovent Biologics, Hengrui Pharmaceutical, and BeiGene firmly occupied the first echelon of domestic PD-1, and are still expanding their indications, and have now covered the treatment scope of melanoma, nasopharyngeal cancer, small cell lung cancer, liver cancer, lymphoma and other large types of tumors.

In this national medical insurance negotiation, in addition to the two nasopharyngeal cancer indications of Carrillizumab of Hengrui Pharmaceutical, the new 8 indications of BeiGene, Innovent Biologics and Junshi Biology have successfully entered the medical insurance. At present, the most included indications in medical insurance is BeiGene, with a total of 5 items.

For Hengrui's new indications failed to be included in medical insurance, the company told the media that in March 2021, carriedivizumab has just been significantly reduced in price, taking into account the cost, new indications and other factors, the two nasopharyngeal cancer indications or will be re-declared together with the newly approved indications in 2022.

Up to now, seven domestic PD-1/PD-L1 drugs have been approved for listing, because the two PD-1s of Chia Tai Tianqing, Yuheng Pharmaceutical and Corning Jereh's PD-L1 have been approved for listing, which is later than the deadline for negotiation, so the opportunity to be included in medical insurance has been missed.

Foreign pharmaceutical companies have failed to enter medical insurance for three consecutive years. Some insiders speculate that the abandonment of medical insurance by imported pharmaceutical companies may be related to the continuous decline in domestic PD-1/PD-L1 prices.

Some pharmaceutical companies have revealed to the health community that the pricing of imported drugs will be set under the global pricing system, and there are certain regulations for the scope of fluctuation.

AstraZeneca's response to the health community was that "information about the business is not convenient for public disclosure".

As for the reasons for not being able to enter the medical insurance directory this time, Merck has chosen to avoid talking about it.

Some pharmaceutical companies have "retreated from difficulties"

In just three years, the domestic PD-1 has changed from a "sky-high drug" of more than 100,000 US dollars to a "cabbage price" of 10,000 yuan. But in this red sea, the giants are still adding chips to bet.

Judging from the degree of R&D progress of existing pharmaceutical companies, it is expected that the number of PD-1 drugs to be listed will exceed 10 in the next three years.

At that time, the fierce competition in the domestic market may be further intensified.

Since PD-1 was included in Medicare, prices have decreased year by year. At the end of 2019, Cinda Bio's xindili monoclonal antibody entered medical insurance at a price reduction of 64%. In December 2020, Cinda launched a relief plan that reduced patient out-of-pocket expenses to 39,800 per two years.

In 2020, BeiGene, Hengrui Pharmaceutical, and Junshi Bio entered medical insurance with an average price reduction of 78%, thereby reducing the annual treatment fee to about 50,000.

The 2021 health care negotiations did not disclose specific prices. According to Ping An Securities, the annual drug dosage amount of domestic PD-1 will be reduced to about 40,000 yuan.

The price trend of falling year by year and the overly concentrated target have greatly compressed the market space, so that the "latecomers" have almost lost the possibility of counterattack.

In early March 2021, BIOTEC announced the termination of the development of PD-1 monoclonal antibody injection. For this move, BIOTEC explained that "the market competition is becoming increasingly fierce".

In just three years, the domestic PD-1 has changed from a "sky-high drug" of more than 100,000 US dollars to a "cabbage price" of 10,000 yuan.

Under the "inner volume" of domestic PD-1 prices, imported pharmaceutical companies have also been forced to make some concessions.

After the medical insurance negotiations in 2020, the price of O drug and K drug has been reduced to 165,000 and 140,000 respectively. This has significantly reduced the "posture" compared with the previous average price of more than 500,000.

Enter the medical insurance must be put in the amount

The exchange of quantity for price has become the core appeal of pharmaceutical companies to enter medical insurance. Especially for innovative pharmaceutical companies, the inclusion of medical insurance can reduce the cost of sales links, thus becoming an important way for them to quickly withdraw funds.

However, in the case of the PD-1/PD-L1 industry alone, access to health insurance does not mean a guarantee of performance.

In the first half of 2021, Hengrui's sales of carried out a negative month-on-month increase.

The imported PD-1/PD-L1 has not entered medical insurance for three consecutive years, which does not mean that it will lose the Chinese market.

As can be seen from the financial reports released by several foreign giants, the sales of imported PD-1s in China are still strong.

The China prescription drug business has become Merck's third largest market. In 2020, the company's revenue from China reached $3.534 billion, up 13% year-over-year.

Merck noted in its third quarterly report that the increase in sales outside the US market was mainly driven by strong demand in the Chinese market.

At present, Merck's K drug has been approved for 8 indications in China, involving 5 major cancers such as melanoma, lung cancer, esophageal cancer, head and neck tumors and colorectal cancer.

AstraZeneca's revenue in China in the third quarter decreased sequentially, but in the sales of I drugs, sales in emerging markets such as China increased by 80% year-on-year.

In this regard, Junshi Bio pointed out that the market for emerging immune checkpoint inhibitor drugs still belongs to the incremental market, and through the exploration of new indications and combination drug strategies, the number of patients suitable for immunotherapy is also increasing, so the sales performance of drugs is also growing.

"At present, the recognition of imported drugs by Chinese doctors and patients is still relatively high. At least on the surface, they will think that imported drugs will be better on some level." An executive of a pharmaceutical company told the health community,

He believes that compared with domestic drugs, imported drugs still have obvious brand advantages. From the perspective of brand, the rapid development of China's biological drugs is only a matter of recent years, and imported drugs have been fully verified at the quality end of drugs through decades of development.

Imported PD-1 is still irreplaceable

In addition to recognition, indications are an important reference for clinicians when prescribing.

Judging from the results of this medical insurance negotiation, domestic PD-1 has added 4 first-line small cell lung cancer and 1 first-line indication for liver cancer.

Does this mean that domestic PD-1 can have the confidence to completely replace imported drugs?

"We must realistically look at the difference between domestic drugs and imported drugs." Some insiders told the health community that the impact effect of domestic PD-1 on imported drugs with a number of new indications remains to be seen, and different innovative drugs have application levels, and medical insurance only plays a basic role in guaranteeing.

In terms of the scope of indications, merck, AstraZeneca and Bristol Squibb passed the preliminary list of 2021 health insurance negotiations for 12 indications in this negotiation.

According to statistics, Merck's K drug has covered 17 cancers and more than 20 indications. Hengrui, which has the most approved domestic drug indications, has only obtained 8.

In the field of PD-L1, the six indications of AstraZeneca and Roche that have been approved for listing in China are all first-line treatments, which have absolute advantages in the treatment of small cell lung cancer at all stages.

"At present, we have passed the stage where we must use imported drugs." Yang Song, chief pharmaceutical researcher of Tianfeng Securities, told the health community that from the perspective of indications, the speed of expanding the scope of domestic drugs is very fast, but because the richness of imported PD-1 data will be higher, patients may consider the choice of drugs according to their own economic situation.

Yang Song stressed: "If there is medical insurance reimbursement, doctors and patients will be more motivated to use."

Sell at the price

Whether from the number of financial reports or the scope of indications, imported PD-1s do not enter the medical insurance, and they are not worried that they will soon lose the Chinese market.

According to the feedback from oncologists, the possible side effects of PD-1 are the most worrying part of doctors' clinical medication.

"In terms of side effects, the gap is still more obvious." Some insiders told the health community that the scope of indications is an important factor, but not the most critical. The core factors in determining the dosage of PD-1 are the efficacy of the drug and the benefits to the patient. The overall gap between domestic PD-1 and imported drugs is not very large, but the gap in side effects is still relatively obvious.

Imported PD-1s remain the first choice recommended by doctors without considering economic considerations.

When holding many favorable advantages in the situation, waiting for the price to sell, may be the current mentality of foreign pharmaceutical companies.

"The gap of 5 to 10 years." This is the judgment of the executives of the pharmaceutical companies mentioned above, who believes that as far as the field of PD-1 is concerned, there is still a gap of 5 to 10 years between domestic drugs and imported drugs in terms of production management and product quality.

It can be seen that the recognition of imported drugs by doctors and patients may not be fundamentally reversed within five years.

Therefore, imported PD-1 may still be very attractive to patients without financial stress for some time to come.

This may be the most fundamental confidence for foreign pharmaceutical companies to abandon medical insurance.

In addition, although the domestic PD-1/PD-L1 is seriously rolled up, it is still far from the brink of "collapse".

A PD-1 industry insider revealed to the health community that the bottom line of domestic PD-1 cost should be between 10,000 and 20,000, assuming that the average price of this medical insurance negotiation will be reduced to about 40,000, then for pharmaceutical companies with ideal cost control, the gross profit margin can still reach about 70%.

"The fundamental reason is that the research and development costs of Chinese drugs are low, and even if the price is sharply reduced, there is still a lot of profit space for the industry's leading enterprises." The above-mentioned industry insiders said.

The domestic PD-1 "inner volume" road may only be halfway through, and it is still far from the final stage of clearing the bubble.

Junshi Bio is full of confidence in the prospects of PD-1, and its tripriplimonumab is the world's first PD-1 monoclonal antibody drug approved for the treatment of nasopharyngeal cancer. It pointed out that after nearly a decade of development, Chinese biomedical companies, especially innovative pharmaceutical companies, have joined the queue of catching up with the world's leading multinational pharmaceutical companies, and even kept up with the pace of developed countries in some disease fields, which is something that the entire Chinese pharmaceutical industry is proud of.

Although the gap exists, I believe that in the next 3 to 5 years, more and more innovative therapy companies from China will enter the top 50 of the global pharmaceutical industry.

Sources | the health community

Written by | Old Zhao next door