Eye-opening clinical data presented on 8 September 2024 in San Diego, CA, USA, at the annual World Conference on Lung Cancer (WCLC) startled the medical world, revealing that a Chinese biotech-created, novel cancer immunotherapy had “crushed” Kenilworth, NJ, USA-based pharmaceutical giant Merck’s record-setting, standard-of-care cancer treatment pembrolizumab (Keytruda®) in HARMONi-2, a large phase 3 randomized controlled trial (RCT) of Chinese patients with advanced non-small cell lung cancer (NSCLC) [
1,
2].
“It is a very impressive result, a 50% improvement in progres-sion-free survival,” said MD/PhD Roy S. Herbst, a lung cancer spe-cialist and deputy director and chief of medical oncology and hematology at the Yale Cancer Center and Smilow Cancer Hospital at Yale University in New Haven, CT, USA.
The trial’s results, subsequently published in the 8 March 2025 issue of The Lancet [
3], mark a first in modern medicine: a China-originated drug significantly outperforming a global, gold standard therapy in a head-to-head, late-stage clinical trial [
3]. They also signal a broader shift. Until recently seen primarily as a manufac-turing base for drug ingredients, China’s pharmaceutical sector is now emerging as a major innovator, helping to shape the leading edge of global drug development.
Currently approved for commercial use only in patents with NSCLC in China, the drug that bested pembrolizumab in HARMONi-2—ivonescimab—was created by Akeso Biopharma (Zhongshan, China); it is now being developed for ex-China markets by Summit Therapeutics (Miami, FL, USA). The drug’s performance persuasively suggests that Chinese-originated biotechnology has the potential to drive medical advances and improve patient outcomes. China’s swift progress in this domain has been driven by multiple factors, such as regulatory reforms that have accelerated drug development timelines and growing homegrown expertise bolstered by the return to China of Western-trained scientists and clinicians. Chinese advantages in advancing novel therapeutics also include the ability to operate with smaller budgets and a lower-cost, highly skilled workforce.
Ivonescimab is undeniably a product of China’s evolved approach to drug development. The drug is a biologic, specifically an engineered, bispecific monoclonal antibody. Conventional mon-oclonal antibodies, like pembrolizumab, mimic natural human antibodies which bind a single antigen target; pembrolizumab and other monoclonal antibodies, the so-called checkpoint inhibi-tors, have become widely used cancer treatments—immunothera-pies—in the last ten years, with lung cancer constituting the largest market [
4]. By contrast, bispecifics are synthetic mono-clonal antibody constructs designed to engage two different anti-gen targets. Like pembrolizumab, ivonescimab (
Fig. 1) binds to programmed cell death protein 1 (PD-1), a cell-surface receptor that dampens immune system responses when bound to pro-grammed death-ligand 1 (PD-L1). Ivonescimab’s second target is vascular endothelial growth factor (VEGF), a ligand that promotes blood vessel formation when bound to its receptor. Akeso scien-tists designed ivonescimab to simultaneously block immune sup-pression and tumor blood vessel formation, thereby enhancing anti-tumor immunity while depriving tumors of blood and nutri-ents (
Fig. 2).
Currently, some cancer regimens used in NSCLC and other can-cers combine multiple drugs to hit therapeutic targets like PD-1 (or PD-L1) and VEGF sequentially or in combination, such as pem-brolizumab combined with bevacizumab (Avastin®), a monoclonal antibody that targets VEGF. Ivonescimab integrates both mecha-nisms into a single molecule. Developed using Akeso’s proprietary Tetrabody® platform [
2], the antibody construct features four anti-gen binding sites and a specially engineered flexible connection intended to improve binding to its targets (
Fig. 3). According to Caicun Zhou, principal investigator of the HARMONi-2 trial, chief physician and director of medical oncology at Shanghai Pulmonary Hospital and Tongji University School of Medicine, and president of the International Association for the Study of Lung Cancer, the design improves the drug’s molecular stability and enhances its selectivity, potency, and safety. “Ivonescimab localizes anti-VEGF activity to the tumor microenvironment, reducing systemic toxic-ity,” said Zhou. “Its configuration produces synergistic anti-tumor activity without off-target effects, as demonstrated by its safety profile in squamous NSCLC and superior efficacy to existing treat-ments in PD-L1-positive disease.”
Conducted in China only, the HARMONi-2 trial compared the safety and efficacy of ivonescimab to pembrolizumab in previously untreated patients with PD-L1-positive advanced NSCLC. The results showed that ivonescimab reduced the risk of disease progression or death by 49% versus pembrolizumab, extending median progression-free survival from about 6 to 11 months [
3]. Its efficacy was consistent across subgroups, including patients with low and high PD-L1 expression, different subtypes of NSCLC, and with and without brain metastases. “Our phase 3 trial redefined outcomes in lung cancer by clinically validating ivonescimab’s dual-targeting mechanism,” said Zhou. “The data supported regulatory approval in China and established ivonesci-mab as a new therapeutic backbone in this setting.” Zhou addition-ally expressed optimism about the drug’s potential for treating other cancers. He said ivonescimab has demonstrated clinical activity in early-stage trials in other solid tumors, including gastric, cervical, and colorectal cancers, suggesting that the drug’s bispecific platform may offer broad therapeutic value beyond NSCLC.
But when the drug might reach patients in the US and other markets is unclear. The key question is whether the progression-free survival benefit will translate to overall survival, said Herbst. “We still need survival data, and it has to come from diverse, global trials—without that, caution remains about the drug’s relevance in the United States.”
Additionally, HARMONi-2 has some important limitations, Herbst noted. The trial did not compare ivonescimab to the current global standard of care in previously untreated advanced NSCLC— pembrolizumab combined with cytotoxic chemotherapy—and that could limit its clinical impact in the United States and other Western countries. Also, because HARMONi-2 was conducted entirely in China, its results will not support a near-term regula-tory filing with the US Food and Drug Administration (FDA); in addition to overall survival results, the FDA generally requires tri-als in more diverse patient populations to grant approval [
2]. To provide the data for a potentially broad FDA approval of ivonesci-mab in patients with previously untreated advanced NSCLC, Sum-mit Therapeutics is currently enrolling two global phase 3 RCTs: HARMONi-3, which compares ivonescimab and pembrolizumab, both combined with chemotherapy, and HARMONi-7, which com-pares the two drugs as monotherapies, like HARMONi-2, but in a more diverse patient population [
1].
Promising topline results from another ivonescimab phase 3 RCT, HARMONi, intended to support the drug’s first US indication, were disclosed in a May 2025 Summit press release [
5]. The trial compared ivonescimab plus chemotherapy to placebo plus chemotherapy in previously treated patients (38% ex-Asia) with epidermal growth factor receptor-positive (EGFR+) advanced NSCLC, a clinical setting with typically poor outcomes for which chemotherapy remains the standard-of-care. The study met its pri-mary endpoint, showing a statistically significant and clinically meaningful 48% reduction in the risk of disease progression or death compared to chemotherapy alone, across both Asian and Western patients [
5]. Although there was a positive trend in overall survival, the trial did not reach statistical significance for this out-come, leaving the drug’s FDA approval for this possibly first US indication in question.
In any case, ivonescimab seems to be just the tip of the spear in terms of investor interest in and strategic licensing activity for Chinese pharmaceutical assets. In 2015, Western pharmaceutical companies made 55 China-related licensing agreements; by 2024, that number had grown to 213—a nearly 4-fold increase [
6]. Large pharmaceutical companies in-licensed approximately 31% of their external pipeline assets from China in 2024, compared to just 10% in 2020 and 3% in 2015 [
7]. These trends suggest that Chinese innovation is increasingly shaping the development prior-ities of major global pharmaceutical companies.
The ivonescimab story provides a good illustration of the grow-ing interest. Summit secured the United States and European Union rights to ivonescimab from Akeso in late 2022 in a deal valued at up to 5 billion USD, including 500 million USD upfront [
8]. Summit is reportedly now in licensing discussions with AstraZeneca (Cambridge, UK) for global commercialization of ivonescimab, in a potential transaction worth 15 billion USD [
5,
9]. Other big companies have quickly jumped on the me-too bis-pecific bandwagon, making substantial outlays for new Chinese drugs similar to ivonescimab. In November 2024, just months after the WCLC HARMONi-2 presentation, BioNTech (Mainz, Germany) announced it had paid 800 million USD to purchase the Chinese biotech Biotheus (Zhuhai, China), with up to an additional 150 mil-lion in potential milestone payments for the PD-L1/VEGF bispecific now known as BNT327 [
10]. For shared rights to this drug, Bristol Myers Squibb (Lawrenceville, NJ, USA) has committed 3.5 billion USD in upfront and near-term payments in a deal worth up to 11 billion USD [
11]. In December 2024, Merck in-licensed a PD-1/VEGF bispecific from LaNova Medicines (Shanghai, China) for 588 million upfront and 2.7 billion USD in potential milestones [
12]. Following suit, in July 2025, Pfizer (New York City, NY, USA) paid 1.25 billion USD to acquire ex-China rights to another PD-1/VEGF bispecific, SSGJ-707, developed by 3SBio (Shenyang, China) [
13].
China’s emergence as a global biotechnology innovator stems from a series of policy shifts, infrastructure investments, and regu-latory reforms over the last decade. “The success of ivonescimab reflects the outcome of a systematic national strategy,” said Xuegong Wang, executive vice director of the China Pharmaceutical Enterprises Association (CPEA), a key national non-profit that represents Chinese pharmaceutical companies and works to promote the industry. “It is the result of long-term structural reforms designed to foster pharmaceutical innovation across China’s biotechnology sector.”
Although the Chinese government identified biotechnology as a strategic priority as early as the mid-2000s, meaningful progress accelerated after 2015, when the National Medical Products Administration (NMPA; formerly known as the China FDA) imple-mented sweeping changes [
14]. These included shortening the investigational new drug review period from 260 to 60 working days, eliminating domestic manufacturing requirements, and aligning clinical trial protocols with international standards. In June 2025, NMPA proposed further halving the review period to 30 working days, matching the timeline used by the FDA and sig-naling a new phase of regulatory agility [
15].
These changes, combined with one of the world’s largest patient populations, lower clinical trial costs, and artificial intelligence-enabled discovery tools, have enabled Chinese biotech companies to rapidly generate robust clinical data on their new drugs. Between 2015 and 2024, the number of active clinical trial centers in China nearly tripled from 375 to 1072; in addition, from 2019 to 2021, the average time from drug registration to trial initiation dropped by more than 40%, from 6.4 to 3.8 months [
16]. China now leads the world in total number of registered drug trials, out-pacing the United States for the first time in 2024, with 7100 trials listed compared to about 6000 for the United States [
17].
The HARMONi-2 trial’s rapid execution—398 patients enrolled across 55 centers in just nine months—highlights China’s emer-gence as a high-speed clinical trial hub, Zhou said. Companies can run global-standard studies within timelines rarely achieved in the United States and European Union. “We have set a new benchmark for operational execution,” Zhou said. “The ability to implement a multicenter trial so efficiently reflects the strength of China’s upgraded clinical infrastructure.”
The recent regulatory reforms have been accompanied by a surge of returning scientists and clinicians trained in the United States and EU—referred to in China as “sea turtles”—who brought experience from multinational pharmaceutical firms and academic research centers [
18]. This influx has helped turn China’s domestic market into a market pursuing fast-follower strategies and devel-oping original therapies [
19]. “In the next five to 10 years, China will remain a key supplier of innovative drug molecules,” Wang said. He acknowledged, however, that despite the sector’s growing influence, basic research investment and the ability to efficiently convert basic scientific research into commercially viable products will be essential to push China further into the top global tier.
Despite the progress, China’s biotechnology sector continues to face substantial hurdles in securing global regulatory acceptance and long-term financial sustainability. Clinical studies conducted solely in China have limited utility for gaining approval by the FDA and other ex-China regulatory bodies, which generally require at least multi-regional clinical trial data [
2]. At the same time, international concerns persist over data privacy, supply chain localization, and intellectual property enforcement in China [
6]. Wang said that regulatory transparency is critical for global trust, and his association is working with the NMPA to align Chinese drug regulation with international standards. The uncertainties have influenced deal structures, with Chinese firms frequently hav-ing received lower licensing fees than their Western counterparts for comparable experimental assets due to risk discounts imposed by global investors [
19].
Even with these pressures, China’s pharmaceutical ambitions have spread beyond oncology. In recent years, Chinese companies have entered high-value therapeutic areas such as obesity and car-diovascular disease, driven by the global demand for weight loss drugs. Regeneron (Tarrytown, NY, USA), for example, signed a deal worth up to 2 billion USD with the Jiangsu Hansoh Pharmaceutical Group (Lianyungang, China) for a weight loss drug that may com-pete with Indianapolis, IN, USA-based Lilly’s market-leader tirzepa-tide (Zepbound®) [
20,
21]. Similarly, Jiangsu Hengrui Pharmaceuticals (Lianyungang) out-licensed three weight loss can-didates to Hercules Pharmaceuticals (Port Washington, NY, USA) in a deal totaling up to 6 billion USD, with 110 million USD paid upfront [
22].
Chinese firms are also working to develop other next-genera-tion therapies. For example, Shanghai Argo Biopharma (Shanghai) has partnered with Novartis (Basel, Switzerland) to develop RNA-based therapies for cardiovascular conditions, a collaboration that included 185 million USD in upfront payment and the potential for 4.2 billion USD in milestone payouts [
23]. Across multiple disease areas, China’s biotech sector appears to have become a strategic source of innovation in areas of clinical need where differentiation and cost efficiency are critical. “Whether the companies there take these drugs all the way or partner with big international pharma-ceutical companies, there is a lot of preclinical and early drug development in China,” said Herbst.
For patients, the accelerating globalization of drug development that China’s progress is driving is likely a good thing. With more countries contributing to the discovery of new treatments, compe-tition could further accelerate innovation and potentially help lower the cost of new, novel therapies. In the ongoing fight to improve the treatment of cancer and other complex illnesses, and perhaps cure them, patients stand to benefit from a world where breakthroughs—like ivonescimab—can come from anywhere.
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