Author丨Ji Yuanyuan.
Editor丨Xu Xu.
Figure source丨Figure worm.
PD-1 PD-L1 checkpoint inhibitors are one of the most dynamic market segments. According to IQVIA data, in the past five years, its performance has significantly outperformed the global oncology market, with a five-year compound growth rate of 45%, which is three times the overall growth rate of oncology, and the global market size reached US$36 billion in 2021 based on manufacturer's ex-factory price.
As the PD-1 PD-L1 market matures, future growth is expected to slow to 15% (5-year CAGR), with IQVIA** global sales of $58 billion by 2025. Although this growth rate is low, it is still ahead of the expected 5-year CAGR of 10% for the overall oncology market.
This trend is also fully demonstrated in Merck's earnings report. According to the 2023 financial report released by Merck, the company's annual revenue is 601US$1.5 billion, up 1% year-on-year, and 9% year-on-year after deducting the impact of the new crown oral drug lagevrio (molnupiravir). Merck Sharp & Dohme's pharmaceutical business revenue was 535US$8.3 billion, a year-on-year increase of 3%, of which China revenue was 67100 million US dollars, occupying 12 of Merck's global market5% share, up 32% year-on-year.
Specifically, from the perspective of products, the performance of drug K (PD-1 inhibitor pembrolizumab Keytruda, trade name Keytruda) is particularly eye-catching. According to the financial report data, K drug achieved annual revenue of 250$1.1 billion, up 19% year-on-year. This performance has already broken the 212 created by Humira (adalimumab) in 2022$400 million in sales record. In addition, according to the 2023 Q3 financial report data released by AbbVie, Humira's sales in the first three quarters were $11.1 billion. In contrast,K medicine will basically lock in the throne of the world's new "drug king", and is expected to pull down Humira, which has been the global "drug king" for 10 years.
In this regard, the chief analyst of the pharmaceutical industry of a brokerage firm told the 21st Century Business Herald reporter that although AbbVie has not yet announced its 2022 financial report, with the expiration of the patent, Humira will encounter multiple challenges in the future market. In this way, Humira not only has to face the pressure of blockbuster products including Merck K, but also has to face the large-scale encirclement and suppression of many generic drugs. Therefore, Humira's revenue in 2023 may be greatly affected, and the throne of "Medicine King" may not be guaranteed.
Previously, AbbVie also publicly stated that it expects its adalimumab franchise to be eroded by about 45% (+-10%) by 2023.
Multinational giants seize market share
In terms of product competition, PD-1 PD-L1 has become one of the more competitive markets.
According to IQVIA data, in 2021, sales of PD-1 PD-L1 inhibitors in the United States accounted for 47% of global sales. As Europe catches up, its share has gradually declined from 60% five years ago, and now the EU-4 and the UK together account for a quarter of the global market. Seven developed markets, including Japan, account for 79% of global PD-1 PD-L1 sales. Despite the rapid pace of adoption, checkpoint inhibitor use per capita in Europe and Japan still lags behind that of the United States, providing greater opportunities to unlock latent demand and expand the PD-L1 market.
In this regard, IQVIA analysis believes that the dynamic trend of the PD-1 PD-L1 market depends on the followingFour aspectsThese four aspects also pose obstacles for latecomers and new entrants:
One is multi-indication. Given its "universal" mechanism of action, PD-1 PD-L1 inhibitors are "one drug equivalent to multiple pipelines". In order to fully exploit its commercial potential, the key to success is to rapidly expand the indications and strategically deploy the indications.
Second, biomarkers are essential for complex PD-1 PD-L1**, for example, to help patients respond to immunity or to ensure the size and patient benefit of the available population. Therefore, the success of checkpoint inhibitors is inextricably linked to biomarker innovation, adoption in routine clinical practice, and testing rates.
The third is market maturity. More than 10 PD-1 PD-L1 inhibitors have been approved for marketing in the global market, and many of these indications are available with a variety of drugs. PD-1 PD-L1 inhibitors, which can be used alone or in combination, are increasingly being used in combination with other cancers**, and the market is becoming more competitive, with more complexities to contend with and opportunities to diverge.
Fourth, keytruda is dominant. Despite the increasing competition in the market, Keytruda remains firmly dominant, with a market share of 54% in 2021. In the current competitive landscape, the position of leading brands still largely reflects the order of market entry.
According to the 21st Century Business Herald reporter,As of February 2, 2024, K has won 39 indications globally and 12 indications in China. Taking the Chinese market as an example, at present, K drug has been approved for indications for multiple cancer types, including lung cancer, head and neck cancer, esophageal squamous cell carcinoma, melanoma, colorectal cancer, gastric cancer, liver cancer, triple negative breast cancer, etc., which is also one of the most approved indications among PD-1 products currently marketed in China. It is understood that the indications of K drug in China are still expanding.
According to Research and Markets**, with the continuous approval of indications and the continuous acceleration of new drug launches, the global sales volume of PD-1 PD-L1 will remain at 23With a compound annual growth rate of 4%, it is expected to reach $50 billion by 2025.
The analysis of Southwest China pointed out that the major indications of various countries and regions are different according to the incidence, and the United States has lung cancer accounting for more than 50% of the market share, which estimates that the overall market size of PD-1 monoclonal antibody in China is expected to reach 30.5 billion yuan. Among them, non-squamous non-small cell lung cancer, gastric cancer (HER2 negative), liver cancer, and squamous non-small cell lung cancer have a total market share of more than 70%, so if you want to seize a place in the PD-1 monoclonal antibody market, you must lay out these large indications.
Accelerate "going to sea" to avoid "involution".
As Merck, the first entrant, accelerates the expansion of indications and market layout, the survival pressure of latecomers intensifies, and the national medical insurance negotiation includes PD-1 product-related indications of leading Chinese and foreign companies in medical insurance, leaving even fewer opportunities for latecomers.
According to the latest National Medical Insurance Catalog, Innovent Biologics' PD-1 inhibitor Tyvyt (sintilimab injection) has been added to the National Medical Insurance Catalog for the seventh indication on the basis of the original medical insurance and will be implemented on New Year's Day 2024 for patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have failed an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)**.
In addition, in China, tislelizumab has submitted a total of 15 indication applications that have been accepted by the Drug Evaluation Center, of which 12 indications have been approved by the State Food and Drug Administration, and 11 indications have been included in the National Reimbursement Drug List, which is currently the PD-1 inhibitor with the largest number of indications approved and included in the National Reimbursement Drug List.
In the face of the current market competition pattern, the first players have to differentiate their layout. To this end, Henlius PD-1 antibody serplulimab, Alphamab Oncology PD-L1 antibody envafolimab injection, and Akeso's PD-1 CTLA-4 bispecific antibody cadonilimab all chose not to participate in the medical insurance negotiations, but to embark on a new market path.
"Going overseas" is considered an effective way to expand the market. To this end, on December 28, 2023, Henlius announced that PT Kalbio Global Medika, a subsidiary of PT Kalbe Genexine Biologics (KGbio), the Company's commercial partner, has received drug registration approval for the drug registration of the anti-PD-1 monoclonal antibody H drug Hansizhuang (serplulimab), independently developed and manufactured by Henlius, has been approved by the Indonesian Food and Drug Administration (BPOM) for use** Extensive-stage small cell lung cancer (ES-SCLC), trade name Zerpidio. This is the first time that drug H has been successfully approved for marketing in overseas markets, and it is also the first time that a domestic anti-PD-1 monoclonal antibody has been successfully approved for marketing in Southeast Asian countries. Currently, Henlius is collaborating with KGBIO on the development and commercialization of H drugs in 22 countries.
Dong Huihui, life science and health industry leader of Grant Thornton Consulting, previously told the 21st Century Business HeraldAlthough it is only by occupying a place in the world that it truly shows its strength, the Chinese market is still the foundation of Chinese pharmaceutical companies. In addition, although many drugs are approved for marketing in other regions after being approved in the United States, which leads to pharmaceutical companies having to go to the United States, the market potential of developing countries such as Southeast Asia and some underdeveloped regions should not be underestimated, and strategic layout needs to be carried out in advance.
But "going overseas" is also the direction that the head PD-1 pharmaceutical companies are aiming at. At present, domestic marketed PD-1 monoclonal antibody companies, including BeiGene, Hengrui Pharmaceutical, Junshi Biosciences and Innovent Biologics, have conducted overseas licensing transactions for PD-1 products. In the case of fierce competition and downward trend of domestic PD-1 monoclonal antibody, the development of overseas rights and interests is a better way out. With the help of the partner's mature overseas sales channels, there is an opportunity to share the global PD-1 monoclonal antibody market.
At present, it is a critical juncture for domestic leading innovative drug companies to go overseas, such as BeiGene, Hengrui Pharmaceutical and other innovative drugs, especially PD-1 L1 monoclonal antibody, which will be approved for marketing in the United States. In this case, if the U.S. health insurance negotiations are successfully implemented, it will make it much more difficult for Chinese innovative pharmaceutical companies to go overseas. We believe that since the current direction of the U.S. medical insurance negotiations is still to account for some of the higher costs of Medicare, the source innovation, differentiated innovation, and multi-dimensional innovation are the king's way for China's innovative drugs to stabilize the internationalization route and avoid vicious competition. Dong Huihui said.
This also means that the successful "going overseas" of PD-1 is not once and for all, and it remains to be seen how to deal with the competitive changes and environmental challenges in the European and American markets in the future.
sfc
The editor of this issue is Zhong Hailing and the intern Tao Tao.
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