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Regardless of the new crown epidemic, in the long history of the world, no Chinese original innovative drugs have entered the list of drugs in the top 10 or even top 20 in sales
.
In the early morning of December 14, Beijing time, BeiGene announced the global phase 3 APLINE trial data of zebratinib in the CLL/SLL indication head-to-head ibrutinib at the annual meeting of the American Society of Hematology (ASH), and the trial was a complete success
80.
4% vs 72.
9% (bilateral P=0.
0264), 24-month PFS 79.
5% vs
67.
3%（P=0.
0024）
。 At the same time, the ALPINE test results were also published in the top international journal "New England Journal of Medicine" (impact factor 176), and obtained the highest international academic recognition
.
.
With this data, BeiGene's zebratinib is poised to rewrite the history of innovative drugs and grow into a global drug
.
Taking stock of the global drug kings in the past nearly 20 years, Lipitor, Humira, and K Pharma are all "latecomers" without exception, but they have all created the same sales miracle
.
Compared with the "old medicine kings", zebratinib has chosen the most difficult "head-to-head" road, on the contrary, it will obtain the blessing of the highest hall level of the international academic community and accelerate its further explosion in overseas markets
.
Ibrutinib, the positive control of the APLINE trial, is also one of the top 10 drugs in global sales for a long time, with sales of about $9.
7 billion
in 2021.
With the complete victory of ALPINE, a global blockbuster drug of Best in Class has been called out
.
.
01 Defeat ibrutinib: "Double Efficacy" is full of gold content, confirming the best in class
01 Defeat ibrutinib: "Double Efficacy" is full of gold content, confirming the best in classShaking ibrutinib to dominate the field of hematological tumors is no easy task
.
The first challenger, acalabrutinib, was launched in 2017, and after five years on the market, product sales peaked to $1.
238 billion
in 2021.
Abrutinib published its clinical data for head-to-head ibrutinib in CLL indications in 2021: the median progression-free survival (mPFS) between the two was comparable, there was no statistical difference, and only non-inferior results
were obtained.
InnoCare's orelabrutinib was approved in 2020, and based on the apparent better BTK selectivity and safety, there is no shortage of market to label orelabrutinib as "potential best in class.
"
BTK inhibitors"
.
At present, InnoCare does not have a head-to-head clinical plan for orelabrutinib, and the economic value of using head-to-head to confirm the efficacy from the time dimension and preemptive order is no longer high
.
Neither acalabrutinib nor orelabrutinib has shown the potential to catch up with or even surpass ibrutinib, which is essentially a lack of clinically confirmed efficacy and safety of the overall efficacy
.
BeiGene's zebratinib is truly the first and only in the world to achieve PFS and ORR for head-to-head ibrutinib in the CLL/SLL process
BTK inhibitors
with double potency.
What does the dual efficacy of PFS and ORR mean for patients?
What does the dual efficacy of PFS and ORR mean for patients?For CLL/SLL as an indolent and incurable hematological tumor, the survival time of patients is often very long, and the "gold standard for tumor evaluation" OS (overall survival) is not suitable for evaluating the efficacy of related drugs, and the clinical benefits of patients should be taken into account
.
Therefore, "PFS+ORR" has become one of the best evaluation combinations, which can not only consider the long-term efficacy and quality of life of patients, but also investigate the impact of drugs on tumors within a certain period of
time.
The latest trial data showed that zebratinib was ORR 80.
4% vs 72.
9% (bilateral P=0.
0264) and 24-month PFS 79.
5% vs
67.
3% (P=0.
0024) The data of the two groups with a clear advantage "outperformed" ibrutinib
.
Another confirms that zebratinib is best in
The consideration factor of Class is that CLL/SLL is more common in middle-aged and elderly people, and the cardiovascular tolerance of patients affects whether they can be continued to take medication
.
The results of the APLINE median follow-up of 29.
6 months showed that the overall incidence of discontinuation of treatment in the zebratinib group was 15.
4%, which was much lower than the 22.
2% in the ibrutinib group, so the safety and tolerability of treatment were higher
.
It is worth noting that the data from this APLINE trial have reliable statistical differences, which set the foundation for the success
of the trial.
Since its launch in 2018, the ALPINE study has enrolled 652 patients worldwide, covering a total of 145 clinical research centers in 15 countries, including the United States, the United Kingdom, China, and Germany, thus ensuring the diversity and representativeness
of trial data in different ethnic groups and regions.
Based on complete and reliable phase III head-to-head clinical data, coupled with the experience of multiple indications of zebratinib in the FDA approval, the FDA's decision to approve the marketing of zebratinib CLL/SLL indications in January 2023 is a high probability event
.
02 "Conquest" of the international academic community, global commercialization accelerated
02 "Conquest" of the international academic community, global commercialization acceleratedWinning the CLL/SLL indications in the United States is crucial
to accelerate the overseas volume of zebratinib.
The overseas medication environment is very different from that in China, and it is very common in China for non-/ off-label drugs, while it is very rare
in the United States and Europe.
On the one hand, doctors strictly follow the instructions for medication, on the other hand, if the drug is not approved for relevant indications or there is no NCCN guideline recommendation, patients cannot be reimbursed, which will cause a greater financial burden
.
At present, zebratinib has not only obtained the dual advantages of efficacy and safety of ibrutinib confirmation in clinical data, but also won the recognition of international authoritative top journals including "New England Journal of Medicine", "Lancet", "Journal of Clinical Oncology", etc.
, which has conquered the international academic community and laid the foundation
for the global mainstream drug market in Europe and the United States.
Among them, the New England Journal of Medicine, as one of the medical journals with the highest influence factor in the world, enjoys a high reputation
in the global medical community.
The results of the ALPINE study were published in the New England Journal of Medicine, which also proves that the international academic community fully affirms
the design, quality control and clinical value of the study.
It is worth mentioning that in this year's updated U.
S.
NCCN guidelines, zebratinib is listed as the highest level recommendation for CLL/SLL and is expected
to be high.
The NCCN guidelines in the United States are internationally recognized as the "gold standard" for clinical practice norms in the oncology community, and are recognized and followed
by clinicians worldwide.
The situation is beginning to tilt
in favour of Zebrutinib.
in favour of Zebrutinib.
Since the beginning of this year, the US FDA and European EMA have successively issued warnings suggesting the cardiovascular risks associated with the use of the first-generation BTK inhibitor ibrutinib, and considering the toxicity of the first-generation BTK inhibitor, the 2023 V1 version of the NCCN guidelines will transfer the recommendation of ibrutinib in the first-line and second-line CLL treatment from "priority recommendation" to "other recommendation"
.
.
At the same time, ibrutinib sales began to decline year-on-year in 2022, with sales of $2.
008 billion in the first half of the year, down 10.
4%
year-on-year.
The decline in ibrutinib sales does not mean the decline of the BTK inhibitor market, after all, its sales have grown much faster than third-party forecasts
in recent years.
According to Fro & Sullivan's data, the global market demand for BTK inhibitors is growing rapidly, and the global market size is expected to reach $21.
9 billion in 2025.
At the same time, the contrast between the data also reveals clear signs
that the market of the old king ibrutinib is gradually being divided and that a strong new king, zebrutinib, is about to rise.
It is not difficult to foresee that the logic of zebratinib sales explosion in the next 2-3 years is very clear
.
.
●
According to the National Cancer Institute, CLL accounts for about a quarter
of new cases each year in all types of leukemia.
Competitor acalabrutinib showed explosive sales growth after approval for this indication in 2019, climbing from US$164 million in 2019 to US$1.
238 billion in 2021;
●
Since 2022, zebratinib's quarterly sales in the United States have shown a continuous sequential growth trend (Q1 to 3 2022: US$67.
9 million\US$88.
4 million\US$108 million), which is enough to prove that its promotion in the European and American markets has opened the situation;
● Up to now, the global commercialization of zebratinib has expanded to more than 60 markets, and more than 40 drug policy applications are under review around the world, covering a wider
and wider range of patients.
03 The success of zebratinib is also the success of BeiGene's globalization strategy
03 The success of zebratinib is also the success of BeiGene's globalization strategyIn 2018, when BeiGene made up its mind to carry out the head-to-head between zebratinib and ibrutinib to the end, it already showed that its strategic positioning and target height were significantly different
from most innovative drug companies in China.
In fact, head-to-head trials and effective results are "hellish difficulty", first, the number of enrolled patients needs to be large enough, the cost needs to be multiplied, the trial time is extended, if the drug is in the critical stage of seizing the first-mover advantage, then it may lose the first opportunity; The second is to directly PK a global TOP10 "miracle medicine", it can be said that the risk is huge, once it fails, all the resources, time, and manpower invested will be burned
.
Pharmaceutical companies not only need to have strong confidence and drug validation level in their own drugs, but also need great courage and determination
.
As one of the core products of BeiGene's innovative drug R&D strategy, the current success of zebratinib not only counters past doubts in the market, but also supports the correctness of
BeiGene's strategic direction to a certain extent.
And this correctness comes from "one center, three directions"
.
One center refers to BeiGene's original intention and goal to move forward step by step towards a global biotechnology company, which determines the company's future height
.
Three directions highlight BeiGene's core R&D capabilities to drive the company's future growth:
●
Fully autonomous end-to-end drug development capabilities: BeiGene currently has more than 3,500 people in the global R&D and medical affairs team, 1,000 of whom are outside
China.
The large and capable drug discovery, clinical development, and commercialization team ensures that BeiGene can fully "de-CXO" and have the full life cycle of drug development system capabilities, which not only ensures the innovation and originality of molecules, but also better controls quality, speed, cost, and takes its destiny into its own hands
.
China.
●
Global MRCT Strategy Amplifies Drug Value: Since 2013, BeiGene has initiated 110 clinical trials in more than 45 countries and regions, of which more than 60% are international multicenter clinical studies enrolling more than 20,000 subjects, nearly half of which are located outside China
.
BeiGene's PD-1 and TIGIT monoclonal antibody have refreshed the licenses of domestic pharmaceutical companies again and again
The record of OUT is no accident, and maximizing the value of each molecule is inseparable from the company's global clinical development strategy and capabilities, which are closely integrated
.
●
Comprehensive new molecular platform + rapid iterative R&D system: In addition to three self-developed products that have already been launched, BeiGene has also built a rich and diversified product pipeline to continue to accelerate the pace
of innovation and iteration.
The company is actively deploying new molecular platforms (covering ADC, CDAC and other platforms), and a number of independent research and development projects are also progressing steadily, including the BCL-2 inhibitor BGB-11417 with differentiation potential, the highly anticipated anti-TIGIT antibody osperlimab, as well as anti-OX40 antibody, HPK1 inhibitor, PI3Kδ inhibitor, etc
.
In the preclinical phase, BeiGene has more than 60 preclinical programs (approximately 50% expected to be first-in-class or best-in-class), and expects to have more than 10 IND applications
per year from 2024.
(Source: BeiGene 2022Q3 Roadshow PPT)
Finally, it must be realized that the sales of zebratinib, as a potential blockbuster product, will also be a huge tempering of BeiGene's global commercialization team, and the company's more blockbuster pipelines will be "seamlessly accessed" in the future, or it can be used to introduce domestic biotech early potential molecules to enrich the pipeline, thereby accelerating the pace
of becoming a global biotechnology company.
Conclusion: Duggan sold Pharmacyclics, which owns the rights of ibrutinib, to AbbVie for $21 billion, and so far AbbVie has achieved more than $40 billion in revenue on ibrutinib and achieved a peak
sales of $9.
78 billion in 2021.
Zebrutinib, who knocked out ibrutinib, will show its best in the next 3 years
The power of class is beyond doubt
.
More importantly, BeiGene, which gave birth to zebratinib, is also moving towards a new stage
of high-quality, international development.
