Redefining Translational Research and China’s Impact on US Drug Development

Evan S. Wu, MD, PhD

Translational researchers in drug development focus on advancing new therapeutics based on preclinical laboratory findings using animal models. This lengthy and costly process often spans several years before a drug candidate progresses from preclinical to first-in-human studies. Enter China. The recent tsunami of drug candidates successfully trialed in humans in China at a blistering pace is creating a new definition of translational research in the United States, one where clinician-scientists are translating early-phase data from China to a US population.

In this 3-part monthly series, I will explore key (and controversial) issues surrounding the translatability of Chinese drug development data to a US population, including the novel concept of bridging studies, the selection of end points in China-to-US translational studies, and racial/ethnic differences in drug metabolism.

In 2024, China accounted for an astonishing 23% of global drug candidates, second only to the United States.¹ The number of oncology drugs developed in China has steadily risen since the launch of the “Made in China 2025” strategic plan in May 2015, with record levels being reported in 2024 and even higher numbers forecasted for 2025.² This initiative aimed to position China as a global manufacturing leader, targeting the industrialization of 20 to 30 innovative drugs by 2025. As of March 2025, the Chinese initiative has well superseded its goal. The success of Chinese drug developers can be attributed to their ability to move rapidly and at a lower cost compared with US counterparts due to competitive advantages in staffing and supply chains.^3,4 Biotech start-ups in China can go from launch to first-in-human data reporting in 18 months or less, compared with a few years in the US.⁵

However, nothing in life is without controversy, and the question of transcontinental applicability looms large. The FDA has historically rejected China-developed cancer drugs when they have been trialed exclusively in China. Geopolitical considerations aside, previous research has shown that racial and ethnic differences can affect the maximum tolerated dose (MTD) in phase 1 clinical trials. For example, studies conducted in Japan have shown differences in MTD for cytotoxic and targeted anticancer drugs between Japanese and Western populations, attributed to both intrinsic and extrinsic ethnic factors.⁶

How do we bridge the gap? The innovative concept of bridging studies plays a crucial role in demonstrating the translatability of China-only early-phase clinical trials to a Western population.⁷ With an increasing share of new drugs originating in China, bridging studies are becoming an integral part of US drug development. Although the goal of oncology drug development is to improve the quantity and quality of life for patients with cancer, the reality is that biotech firms face immense pressure to bring drugs to market as swiftly and efficiently as possible. Bridging studies accelerate global drug approval by supplementing existing data with region-specific findings. Successful bridging studies that prove translatability from China to the US must enroll a diverse US population including Black and Hispanic patients, show pharmacokinetic (PK) and pharmacodynamic similarities across racial/ethnic groups, and confirm that efficacy and safety align with those observed in the original study. These elements are crucial for a bridging study to achieve the ultimate goal of a successful biologics license application with the FDA.

As coprincipal investigator of the Henlius-sponsored, phase 3 ASTRIDE clinical trial (NCT05468489) for small cell lung cancer (SCLC), I have had firsthand experience with the complexities of bridging studies. The ASTRIDE trial seeks to demonstrate the applicability of data from the global but China-majority phase 3 registrational ASTRUM studies to a US-only population. ASTRUM-004 (NCT04033354) and ASTRUM-005 (NCT04063163) successfully established that the PD-1 inhibitor serplulimab, in combination with chemotherapy, improved overall survival (OS) and progression-free survival in patients with advanced squamous non–small cell lung cancer and extensive-stage SCLC, respectively, compared with chemotherapy alone.^8,9 Despite the inclusion of 31% White patients from Europe in ASTRUM-005,⁹ the FDA raised concerns due to the absence of US participants and the lack of representation from Black and Hispanic populations in the registrational study. In response, the FDA recommended that Henlius collect additional data to demonstrate the relevance of ASTRUM’s findings to US patients. After careful deliberation and design consideration, the ASTRIDE bridging study was conceived. This 2-arm descriptive study would enroll 100 patients per arm, with one group receiving serplulimab plus chemotherapy and the other receiving atezolizumab (Tecentriq) plus chemotherapy.

The success of bridging studies such as ASTRIDE depends on leveraging previously reported clinical trial data. The FDA approved the descriptive study design for ASTRIDE, rather than a superiority study, because the global ASTRUM trials had already validated the efficacy and safety of serplulimab plus chemotherapy in a large, non-US cohort. The primary objective of ASTRIDE is to confirm the applicability of ASTRUM’s findings to the US patient population by demonstrating similar safety, efficacy, and PK data, without the aim of proving statistical superiority or noninferiority. Although the concept of a descriptive bridging study may seem unconventional to clinical trial purists, the rapid pace of Chinese drug development and the FDA’s commitment to providing the US population with the most effective therapies available globally serve as motivating drivers for this flexible study design.

In the next article, I will examine the challenges associated with clinical end point selection and trial design in bridging studies, particularly in cases where preexisting data are limited to Chinese patients or when OS is not a logistically feasible end point for cancers with a favorable prognosis. I will explore the most efficient strategies for translating data from China to the US in these more complex scenarios.

Evan S. Wu, MD, PhD, is an assistant professor at the University of Hawai’i Cancer Center.

References

1. A decade of innovation, a decade to come. Life Sciences & Healthcare, Clarivate. November 2024. Accessed April 9, 2025. https://clarivate.com/life-sciences-healthcare/wp-content/uploads/sites/4/dlm_uploads/2024/11/Clarivate_10-years-of-Innovation-in-China_Report.pdf
2. Conroy G. How ‘Made in China 2025’ helped supercharge scientific development in China’s cities. Nature. Published online November 20, 2024. doi:10.1038/d41586-024-03522-y
3. Chen C, Lou N, Zheng X, Wang S, Chen H, Han X. Trends of phase I clinical trials of new drugs in mainland China over the past 10 years (2011-2020). Front Med (Lausanne). 2021;8:777698. doi:10.3389/fmed.2021.777698
4. Zhang J, Zhang P, Wang H, Dong R. Changes in early-phase clinical trials in China during 2013-2022: a review. Drugs R D. 2024;24(3):383-390. doi:10.1007/s40268-024-00489-z
5. Fidler B. ‘The bar has risen’: China’s biotech gains push US companies to adapt. BioPharma Dive. January 16, 2025. Accessed April 9, 2025. https://www.biopharmadive.com/news/biotech-us-china-competition-drug-deals/737543/
6. Maeda H, Kurokawa T. Differences in maximum tolerated doses and approval doses of molecularly targeted oncology drug between Japan and Western countries. Invest New Drugs. 2014;32(4):661-669. doi:10.1007/s10637-014-0080-y
7. Zheng H, Hampson LV, Jaki T. Bridging across patient subgroups in phase I oncology trials that incorporate animal data. Stat Methods Med Res. 2021;30(4):1057-1071. doi:10.1177/0962280220986580
8. Zhou C, Hu Y, Arkania E, et al; ASTRUM-004 Investigators. A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004). Cancer Cell. 2024;42(2):198-208.e3. doi:10.1016/j.ccell.2023.12.004
9. Cheng Y, Han L, Wu L, et al; ASTRUM-005 Study Group. Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer: the ASTRUM-005 randomized clinical trial. JAMA. 2022;328(12):1223-1232. doi:10.1001/jama.2022.16464