The first domestically produced "billion-dollar molecule" was spent in BeiGene.
Recently, BeiGene announced its 2023 financial results, in which the global sales of BTK inhibitor zanubrutinib reached US$1.3 billion, exceeding the US$1 billion mark for the first time and becoming a "blockbuster" drug.
So, after zanubrutinib, where does the next domestic "billion-dollar molecule" come from?
BeiGene still has a "billion-dollar molecule"?
If a drug has annual sales of more than $1 billion, it will be called a "blockbuster" drug.
But it's not easy to create a "blockbuster" drugIt is not only necessary to see the R&D strength of pharmaceutical companies and whether the drugs have the best ability to change, but also to test the global business layout.
Although many breakthrough drugs have been developed by domestic pharmaceutical companies, due to the initial road of globalization, "blockbuster" drugs are only exclusive to multinational pharmaceutical giants.
But now, with BeiGene's zanubrutinib becoming the first domestic "billion-dollar molecule",The history of domestic innovative drugs without "blockbuster" drugs has been rewritten.
What's more worth mentioning is that it usually takes about 10 years for a drug to become a "blockbuster" drug from being approved for marketing. It took only 3 years for zanubrutinib to be approved by the US FDA in November 2019 to become a "blockbuster" drug, and its sales have grown rapidly.
The reason for this is, on the one hand, zanubrutinib has the best transformative ability, with better efficacy and safetyBeat ibrutinib in a head-to-head trial and establish itself as a best-in-class drug in the world.
On the other hand, BeiGene has built a global commercialization team of more than 3,500 people thanks to its extensive commercial presence in the global market, and zanubrutinib has been approved for multiple indications in more than 65 countries and regions around the world, making it the BTK inhibitor with the widest indication coverage.
Of course, the water is big and the fish is big, and the soaring sales are not only inseparable from the improvement of the company's strength, but also benefit from the growth of market demand. According to the Frost & Sullivan report, the global and Chinese markets for BTK inhibitors will grow to US$20 billion and 13.1 billion yuan respectively in 2025.
BeiGene has a global commercial footprint and a rich pipeline pipelineThere is a high probability that the next "billion-dollar molecule" will be born.
For exampleTislelizumab, with sales of 5$300 million, which is expected to sprint "blockbuster" drugs.
Tislelizumab has significant product advantages, and is currently the PD-1 monoclonal antibody with the largest number of approved indications and the largest number of indications included in the NRDL in China, and is being developed in conjunction with more than 40 molecules**.
In addition, the global commercialization of tislelizumab is also accelerating, and it has been approved in the European Union and the United Kingdom, and is expected to successfully pass the US FDA within this year, and is also undergoing regulatory review in 10 markets around the world, and the market potential should not be underestimated.
What's more, the era of PD-1 monoclonal antibodies is not over, not only the current "global drug king" is Merck K, but BMS's O drug has also successfully ranked among the top 10 best-selling drugs in the world in 2023.
In addition to this,Sonrotoclax (BGB-11417) also has the potential to be a "blockbuster" drug.
Sonrotoclax is a second-generation highly selective and potent BCL-2 inhibitor that has shown potent activity over venclexta in previous studies and may have the potential to overcome venetoclax resistance. As a result, BeiGene initiated a clinical trial of sonrotoclax head-to-head venetoclax, and it is uncertain whether it can replicate the success of zanubrutinib.
VenetoclaxIt is currently the only BCL-2 inhibitor on the market in the world, and has maintained a good growth trend in recent yearsSales in 2023 will reach 22$8.8 billionA year-on-year increase of 139%, AbbVie expects peak sales to reach $6 billion.
Compared with marketed BCL-2 inhibitors, Sonrotoclax has a shorter half-life and no drug accumulation, which is expected to lead to a better safety profile. Moreover, Sonrotoclax also has a layout from single agents** to combination drugs, covering multiple indications of B-cell malignancies.
However, there is also pressure on Sonrotoclax, with Genta's Olimerson filing for marketing, Ascentage Therapeutic's LisaftoClax, AbbVie's N**itoclax and Teva's Obacla, all of which are in Phase III clinical trials.
Potential domestic "billion-dollar molecule".
As mentioned earlier, a drug wants to become a "blockbuster" drug with annual sales of more than $1 billionIt needs to be proven to be a "best-in-class" in the world through head-to-head trials, and it needs to be suitable for a large number of patients and have a large enough market space.
For domestic pharmaceutical companies, if they want to create a "blockbuster" drug, they must be able to invest a lot of R&D funds, especially with global business layout capabilities, or cooperate with multinational pharmaceutical companies with strong marketing strength.
For exampleGenScript Biotech's Legend Biotech has joined hands with Johnson & Johnson, which is a typical case of going overseas.
In December 2017, Legend Biotech and Johnson & Johnson reached a 3$500 million down payment partnership agreement to share BCMA CAR-T**carvyktidevelopment, manufacturing and commercialization rights. In 2022, Carvykti ushered in commercialization, and was successively approved for marketing in the United States, the European Union and Japan.
With BIC's product advantages and Johnson & Johnson's strong commercialization strength, Carvykti will continue to increase its volume after its launch, with total sales reaching US$500 million in 2023, a year-on-year increase of 276%.In the future, it may break through the $1 billion mark and become a "blockbuster" drug.
In fact, for domestic pharmaceutical companies that do not have a lot of cash on their books, there are not many pharmaceutical companies that can build their own global commercialization teams like BeiGeneTherefore, it is common to choose to cooperate with multinational pharmaceutical companies to complete the overseas expansion.
Since the commercialization of overseas markets can be handed over to multinational pharmaceutical companies, domestic pharmaceutical companies can focus their energy and funds on R&DCreate a "blockbuster" drug by conducting head-to-head trials.
For example, Akeso has developed the world's first PD-1 VEGF bispecific antibodyIvoximab (AK112).A phase clinical trial of a head-to-head K drug single-agent first-line **PD-L1-positive NSCLC, and a phase clinical trial of a head-to-head tislelizumab first-line **sqNSCLC in combination with chemotherapy.
Although ivoximab has not yet been approved for marketing, Akeso has entered into an overseas licensing collaboration with Summit for the drug of up to US$5 billion, and received an upfront payment equivalent to US$500 million in the first half of 2023.
Innovent has developed GLP-1R GCGR agonistsIBI362 (Masdotide).A phase III trial of head-to-head semaglutide in patients with early-stage type 2 diabetes and obesity; Columbotai completes the TROP2 ADC drugskb264（mk-2870）A head-to-head study of Gilead trodelvy (gosatuzumab) showed improved safety and efficacy.
In May 2022, Columbus granted the overseas rights and interests of SKB264 to Merck & Co., Ltd. for more than US$1.4 billion, and the latter has initiated three Phase III clinical trials around SKB264, as well as conducting trials in combination with K-drug** for multiple solid tumors.
In addition, Yifan Pharma aims at the world's first third-generation long-acting G-CSFElishu (F-627, ibersim injection).A head-to-head study of neulasta (filgrastim) was conducted. Among them, Neulasta is Amgen's blockbuster drug, with peak sales of $4.7 billion.
In terms of commercialization strategy, Yifan Pharma granted the sales rights of Yilishu in China to Chia Tai Tianqing, a Chinese biopharmaceutical subsidiary. In November 2023, Yilishu was approved by the US FDA for the treatment of neutropenia in ** cancer patients after receiving anti-cancer drugs, and is expected to be marketed in the United States in mid-2024, and will expand to Europe, Brazil and Japan and other markets in the future.
Domestic innovative drugs go overseas to hit a new high
Brewing "blockbuster" drugs
According to the idea of domestic innovative drugs going overseas, some potential "billion-dollar molecules" can also be tapped.
Especially in the past 2023, the scale of foreign licensing cooperation of China's innovative drug companies has reached a record high, with a total of 70 license-out transactions occurring throughout the year, an increase of 32% from 44 in 2022. The total value of disclosed transactions exceeded US$46.5 billion, an increase of 69% from US$27.6 billion in 2022.
According to the Galaxy** research report, in 2023, there will be nearly 20 domestic innovative drug license-out transactions with a total amount of more than US$1 billion, covering monoclonal antibodies, bispecific antibodies, differentiated ADCs, bispecific antibody ADCs, CAR-T** and mineralocorticoid receptor antagonists.
Among them, the top five BD projects in terms of total transaction amount are awarded to BMS by Baili TianhengEGFR HER3 bispecific antibody ADC drug BL-B01D1, Chengyi Biotech awarded to AstraZenecaOral GLP-1RA drug ECC5004, Briliscone awarded to EisaiHER2 ADC drug BB-1701, Hansoh Pharmaceuticals awarded GSKB7H3 ADC drug HS-20093, as well as two drugs awarded by Hengrui Pharmaceutical to Merck KGaASecond-generation PARP inhibitor HRS-1167cldn18.2 ADC drug SHR-A1904
It is not difficult to see that the types of drugs that have reached high-value BD transactions are basically the current popular ADC and GLP-1 drugs. This means that in the future, domestic "billion-dollar molecules" may have a place for these popular drugs.
Taking GLP-1 drugs as an example, Novo Nordisk's semaglutide sales in 2023 will reach 21.2 billion US dollars, which is not much different from the first "global drug king" K drug (25 billion US dollars), and is undoubtedly the strongest contender for the next drug king.
Not only that, Eli Lilly's tirpatide (Mounjaro) sales in 2023 will achieve a growth rate of 51 with a growth rate of 970%.$6.3 billion, sales growth rate far exceeded semaglutide.
Under the tuyere of GLP-1, Chengyi Biotech awarded AstraZeneca's oral small molecule GLP-1 drug ECC5004, which also has the industry endorsement of impacting the "blockbuster" drug.
Of course, reaching overseas cooperation with multinational pharmaceutical companies is only the first step in the long march, and there are still many difficulties to overcome whether the follow-up can truly become a "blockbuster" drug.
At present, zanubrutinib has created a new history, which undoubtedly adds confidence to the growth of domestic innovative drugs and the development of the international market.
References: 1Financial reports, announcements, and official websites of each company.
2."BeiGene 2023: Zanubrutinib's Global Revenue Exceeds $1 Billion for the First Time," Insight, 2024-02-26
3."Pharmaceutical Industry 2024 Investment Strategy Report: Innovative Drugs, Valuation Bottom, Grasp Multi-Main Line Opportunities-231230", China Securities Construction Investment**.
4."20240104-Pharmaceutical Industry Monthly Report: Accumulation of Innovative Drugs, Looking Forward to Policy Support", Galaxy** Hot Engine Program