"The morning market is good"
As the year draws to a close, the atmosphere that pervades the PD-1/PD-L1 market is less festive.
On December 21, CStone's PD-L1 schuglimab was officially launched. So far, the domestic market PD-1/PD-L1 products have reached 12 models, and 8 varieties are made in China.
The industry no longer talks about "inner volume", but says: We all need PD-1.
The saying of "joint use", like the "universal anti-cancer drug" of that year, is easy to be beaten by the market and cannot find teeth, and everyone understands this truth. As a result, some pharmaceutical companies began to strive to prove that they were "optimal".
On December 16, Chia Tai Tianqing's self-developed PD-L1 monoclonal TQB2450 and anlotinib conducted a head-to-head phase III clinical trial against Baekje PD-1 terelizumab. This is the second head-to-head trial launched by Chia Tai Tianqing for its own product, and the other control is Merck's K drug pambolizumab.
For many years, K-drug has not entered the medical insurance, and this year it has not even participated in the medical insurance negotiations, but it is still a "god-like existence" in the PD-1 field. In the 7 years since its listing, K-drug has won 29 indications, and its sales far exceed other varieties. Nibbling on K medicine has become the ideal of PD-1/PD-L1 at home and abroad.
According to the rough statistics of the Health Bureau, including Hengrui, BeiGene, Junshi, Xinda, and Lepu, many domestic companies have carried out head-to-head or controlled trials of K drugs.
Pharmaceutical companies are very calm in their mouths, but their bodies are very honest:
There is no special room for competition in the PD-1 field, only to squeeze out opponents.
White Moonlight K Medicine
An interesting statistic is that since 2021, K-drugs used in the control group may have treated more than 500 cancer patients.
The status of K medicine in terms of efficacy is indeed difficult to shake.
Since 2018, the sales of K-drug have won the PD-1/PD-L1 market for three consecutive years. In 2020, K-drug sold a total of $14.38 billion worldwide, more than 2 times higher than the second-place O drug.
Especially in November, the CDE's guidelines on clinical research and development of tumor drugs were officially implemented, and "positive control" became a mandatory option. In the future, only drugs that prove their "efficacy" can be recognized, which makes the threshold for the listing of tumor drugs higher.
Like Chia Tai Tianqing, before it was listed, he began to think about "head-to-head", and he was also destined.
As early as July this year, when the draft of the new CDE regulations was released, the head of research and development of pharmaceutical companies told the Health Bureau: This is actually a hint that some small pharmaceutical companies should change their thinking and not "die" on PD-1 and other internal roll targets.
However, there are not many companies that can stop losses in time like Lilly did in that year. The risks and costs of head-to-head trials are clear, and many domestic PD-1/PD-L1 that have been listed can only choose K drugs as control drugs.
The person in charge of R&D of the above-mentioned pharmaceutical companies believes that the current domestic PD-1/PD-L1 competition is actually testing the commercialization ability. If you just want to take the indications, you don't necessarily need to do head-to-head.
"The more important purpose of head-to-head development is to explore overseas, especially the US market."
Another pharmaceutical company also confirmed to the Health Bureau that due to the differences in the data results of different races, if there is overseas enrollment data, it will be more internationally recognized.
It is also not safe at sea
The consensus among all businesses that PD-1 needs to go out to sea is the consensus of all businesses; but on the other side of the sea, the FDA is tightening access rules.
On December 20, Cinda Bio held an online meeting to urgently respond to rumors about the tightening of the PD-1/PD-L1 drug listing policy in the United States. Instead, Innovent Bio responded that the process of sindilizumab going to sea "is proceeding according to the planned schedule, and the company is confident in the efficacy of the drug."
Previously, Based on the phase III clinical data conducted in China, Innovent Biologics submitted a listing application for Sindilimab to the FDA, and did not include a sufficient number of overseas patients. In response, the FDA launched an external expert vote.
More importantly, in mid-December, two of the FDA's top cancer doctors jointly posted in the New England Journal of Medicine that the global PD-1/PD-L1 market has become redundant, but the data shows that there are still more than 2,000 clinical trials in progress. Among the indications that have been listed, 45% choose to apply for accelerated approval of listing in one-arm trials first, and then make clinical confirmation.
The consequence of taking shortcuts is that the data results are inconsistent.
The Health Bureau noted that Roche, AstraZeneca, Bristol-Myers Squibb (BMY.US) and Merck's four major PD-1/PD-L1 companies had all "voluntarily withdrawn their applications for the indication" because the follow-up verification test did not reach the end point.
"The industry should curb excessive enthusiasm for research and development and not obsess over the development of me too drugs." Two FDA experts bluntly said that if companies are really doing "effective" products as they say, they will directly do head-to-head trials.
According to industry analysts, this is actually not to encourage everyone to really blindly do head-to-head, but hope that companies will calm down and refocus on the quality of drugs themselves.
Compared to the one-arm test, the cost of head-to-head is much higher. Most domestic innovative pharmaceutical companies do not have any clinical teams overseas, and can only choose to outsource their projects to CRO companies, which invisibly increases costs.
The above-mentioned pharmaceutical companies estimate that according to the current cost in China, the average cost of clinical trials on each patient ranges from 300,000 yuan to 500,000 yuan. However, if an international multicentre trial of K drugs is carried out, the cost will be much higher.
At present, the annual cost of domestic K drugs is 179,000 yuan, so it is estimated that more than 300 people in Phase III clinical trials, just buying control drugs will cost tens of millions. If it is an overseas head-to-head clinic, the cost of buying drugs may be hundreds of millions.
Losers of head-to-head trials have a hard time gaining a foothold in the market anymore. Earlier this year, Merck announced the termination of phase III clinical trials for non-small cell lung cancer in contrast to K drugs for PD-L1/TGFβ. Originally pinned on to become the star product of the second-generation PD-1, it lost a large number of loyal fans.
On the issue of going to sea, the first echelon of PD-1 production enterprises in China have chosen to authorize abroad. For example, Baekje and Novartis, Cinda and Eli Lilly, Junshi and Coherus have transferred the risk and pressure of marketization to major international pharmaceutical companies. At present, this is also a channel where everyone is squeezed out.
"It's so nice to be in the morning." A pharmaceutical company person lamented about the Health Bureau.
Text | Ancient Moon
Operational | Twenty-thirteen
Two in-depth manuscripts per day to decode medicine and health
#国内PD-1 pharmaceutical company ##国内上市药企 #