From Zebutinib to Obstinib, BeiGene and Nuocheng Jianhua's global commercialization prospects

Recently, BeiGene announced that the interim analysis of a global Phase III SEQUOIA trial of its BTK inhibitor Zebutinib has achieved positive main results, and the study has reached its primary endpoint
.

The clinical results showed that Zebutinib significantly prolonged the progression-free survival of newly treated patients with chronic lymphocytic leukemia (CLL), and demonstrated good safety and tolerability.

I believe that every medical person is familiar with Zebutinib.
Zebutinib was approved by the U.
S.
FDA two years ago and became the first anti-tumor innovative drug independently developed by a Chinese company and approved for marketing in the United States.
Jeshenju also fired the first shot of a local innovative drug company in the global commercialization
.

It is precisely because of Baekje's jade that has emerged in the past two years that more and more local innovative companies have chosen to set sail in the United States and seek the path to the global commercialization of new drugs

As the first innovative drug approved for marketing in the United States, Zebutinib has also attracted countless industry spotlights.
Whether it is multinational pharmaceutical companies across the ocean or many Biotech successors in China, they are all paying attention to Zebutin.
Nissan’s commercialization performance in the global market for BTK inhibitors
.

The past two years have passed.

Global market overview of BTK inhibitors

BTK (Bruton's tyrosine kinase) is a member of the Tec family of tyrosine kinases
.

It is expressed in all hematopoietic cells except T cells and terminally differentiated plasma cells .

It did not take long for BTK inhibitors to be converted into commercial drugs.
It was aimed at this promising target.
AbbVie and Johnson & Johnson took the lead.
The BTK inhibitor Ibrutinib jointly developed by the two parties was developed in 2013.
It was approved for listing in the year and became the world's first BTK inhibitor to be marketed
.

Up to now, Ibrutinib has been approved for many indications including mantle cell lymphoma (MCL), chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) and Waldenstrom's macroglobulinemia (WM)

In order to improve off-target effects and poor BTK selectivity, major pharmaceutical companies have also focused on developing a new generation of BTK inhibitors with different binding characteristics and improved selectivity
.

Up to now, 5 BTK inhibitors have been approved worldwide.

From the sales in the above table, it is not difficult to see that Ibrutinib's performance in the BTK inhibitor market is still outstanding.
Since its approval, the sales of Ibrutinib have also made a qualitative leap year by year
.

According to statistics, in 2014, the sales of ibrutinib was US$692 million.

Compared with the very eye-catching sales data of ibrutinib, the sales of acatinib are still a little different at present
.

In 2017, the sales of acatinib were US$03 million, and in 2020 it reached US$520 million

Facing the current market share firmly occupied by multinational companies, BeiGene and Nuocheng Jianhua have also chosen completely different paths on the road to global commercialization
.

BeiGene-Do it if you don't accept it, confront it head-on

In addition to the SEQUOIA clinical trial mentioned above, BeiGene also released the results of another ALPINE head-to-head clinical trial of Zebutinib at the European Society of Hematology this year
.
Clinical results show that, compared with ibrutinib, zebutinib is used in the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma, in the primary endpoint of the study , The overall response rate (ORR) assessed by the investigator, and the key secondary endpoint atrial fibrillation or atrial flutter event rate showed superiority
.

And this is currently the only study that has shown better efficacy than ibrutinib in a more selective BTK drug
.
With clinical data superior to ibrutinib, zebutinib ushered in a good opportunity for rapid development.
Some analysts pointed out that with these clinical data, BeiGene can simultaneously seek FDA approval for zebutinib for first-line use.
And second-line chronic lymphocytic leukemia, thereby avoiding the indications of other BTK inhibitor drugs, positioning Zebutinib as a key BTK inhibitor in the treatment of chronic lymphocytic leukemia, so that BeiGene has a differentiated commercial advantage New opportunities
.

And this opportunity is also a historic breakthrough that Baekje has made after a long time of careful global deployment.
It is not difficult to see from the clinicaltrials.
gov website that Zebutinib has conducted a number of clinical trials on a global scale.
There are 29 clinical trials registered in the United States
.
It is also learned from the company's official website that there are currently more than 30 related listing applications for zebutinib for multiple indications, covering the United States, the European Union and more than 20 other countries or regions
.

However, on the way forward, it seems that it is not so easy for Baekje to complete the global commercialization of new drugs after the launch of new drugs in the face of multinational companies that have been in the global market for many years
.
Compared with Baekje, AbbVie, Johnson & Johnson, and AstraZeneca obviously have better resource allocation and business execution capabilities.
The current sales also confirm this.
In the second quarter just past, Zebutinib Sales of 42.
4 million U.
S.
dollars, although achieved a relatively high sales growth rate, but the main sales are still contributed by domestic
.

Although the current rapid growth of acatinib also shows that the first-mover advantage of ibrutinib in chronic lymphocytic leukemia is not insurmountable, but due to the inherent limitations compared with many multinational companies, it also makes a hundred of clinical advantages in hand.
It is difficult for the economy to make waves in a short period of time
.
Perhaps because of this, Baekje also licensed out the company’s PD-1 product commercial development rights in the United States and other countries to Novartis at a high price of $2.
2 billion this year
.

How to transform clinical advantages into market share is a problem that will not only cause problems for Baekje for a long time in the future, but also bring deep thinking to local innovative companies that want to go global.
How to break the game will also become this problem.
The only way for enterprises
.

Nuocheng Jianhua-win steadily, license out

Compared with Baekje, Nuocheng Jianhua has chosen a more prudent path.
In July this year, Bojian/ Nuocheng Jianhua reached a license and cooperation agreement on the BTK inhibitor obritinib, and Bojian won the Olympic Games.
Butinib has the exclusive global commercialization right in the field of multiple sclerosis (MS).
The transaction value can reach up to 940 million US dollars, setting a new record for the license-out of new small molecule drugs in China
.

Unlike zebutinib, obetinib has not done a head-to-head clinical trial.
In view of the current head-to-head studies carried out by acatinib, zebutinib and ibrutinib, ibrutinib has not yet been taken away.
Nuocheng Jianhua considers how to maximize the Me-better features of abutinib
.

The clinical data of abutinib is very powerful.
In the treatment of chronic lymphocytic leukemia, the efficacy of abutinib is even better than other BTK inhibitors.
The overall response rate (ORR) is much higher than that of other BTK inhibitors and complete remission.
The CR is also a great success, which means that a considerable number of patients can achieve clinical cure
.
In addition, Obutinib has the characteristics of being able to penetrate the blood-brain barrier, achieving high target occupancy in the central nervous system, and potential clinical benefits in the treatment of central nervous system diseases.
According to the current data, it is superior to Merck’s Evobrutinib and Evobrutinib.
Sanofi’s SAR442168.
This is also the key reason why Biogen is still willing to invest heavily in the introduction of Obrutinib even though it is in the early stage of research in the MS field
.

Just last week, Nuocheng Jianhua announced that it has officially launched a phase II global clinical trial of obritinib for the treatment of MS.
With Bojian’s mature clinical development capabilities in the field of MS and the advantages of global commercial network resources, obritinib is in The commercialization prospects of MS indications will be more promising
.
Nuocheng Jianhua regards the license-out of the global rights and interests of obritinib for MS indications as a wise move, which not only realizes the commercial value, but also optimizes its resource allocation in other product pipelines, highlighting a word of stability.

.
In addition, this move can also help raise Nuocheng Jianhua's global awareness, which is also of great benefit to its global commercialization process
.

To sum up, whether it is BeiGene, which is more adventurous and chooses to fight alone, or Nuocheng Jianhua, who chooses to cooperate with giants in a stable manner, they all provide excellent cases for the global commercialization of local innovative companies.
It is worthy of admiration and deep thinking
.
Although the road is long, I hope to get the same result by different routes
.

Reference materials:

Reference materials:

1.
Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects, doi: 10.
3389/fcell.
2021.
630942;

1.
Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects, doi: 10.
3389/fcell.
2021.
630942;

2.
BeiGene tees up 3-way leukemia competition against J&J-AbbVie, AstraZeneca with Brukinsa win, from https:// tees up 3-way leukemia competition against J&J-AbbVie, AstraZeneca with Brukinsa win, from https:// 3.
Medicine Rubik's Cube: The logic behind the $940 million transaction of Bojian/Nuocheng Jianhua;

3.
Medicine Rubik's Cube: The logic behind the $940 million transaction of Bojian/Nuocheng Jianhua;

4.
Public information on the official website of BeiGene and Nuocheng Jianhua
.

4.
Public information on the official website of BeiGene and Nuocheng Jianhua
.