On August 8, 2026, the U.S. FDA approved RiboX Therapeutics' RXIM002 IND. This is the world's first circular RNA-based in vivo CAR-T therapy, and it secured FDA clearance based on safety and efficacy data generated from an investigator-initiated trial conducted in China.
The FDA reached its review decision after a complete evaluation of all IIT data, including one serious adverse event. This itself constitutes a de facto acknowledgment: the quality of Chinese IIT data is now being accepted by one of the world's most stringent regulators for use in registration.
Chinese IITs: From Exploration to Translational Registration
As early as 2017, Legend Biotech's LCAR-B38M, later known as Carvykti, was based on single-arm IIT/IND data generated in China, leading to a global partnership with Johnson & Johnson and eventual FDA approval, becoming a landmark case for Chinese innovative drug out-licensing. In 2024, AstraZeneca acquired EsoBiotec, whose early-stage pipeline was also built on in vivo CAR-T technology originating from the Chinese IIT.
From Carvykti to EsoBiotec to RXIM002's FDA IND, Chinese IITs are transitioning from early-stage exploration to the pre-registration stage of global regulatory review.
Behind this progress lies a systematic upgrade in China's clinical research capabilities. Over the past decade, China's clinical trial site capacity, ethical review systems, and investigator familiarity with GCP/ICH standards have improved dramatically. The State Council's Decree No. 818, the Regulations on the Administration of Clinical Research and Translational Application of Biomedical New Technologies, which took effect on May 1, 2026, has set clear quality standards for IITs at the regulatory level: research must be conducted at Class 3A hospitals, and study records and original materials must be retained for 30 years.
Since Decree No. 818 took effect through mid-July 2026, registered clinical research have continued to expand, and the ecosystem has entered a phase of higher-quality development. According to Huang Yegui, Secretary-General of the Cell Therapy Federation at the Zhongguancun Jianzhong Chronic Disease Diagnosis and Treatment Innovation Center, a total of 93 biomedical new technology clinical research have been filed across six batches nationwide, with over 800 applications currently in the pipeline. In the sixth batch of 13 projects, immune cell therapies matched stem cell therapies in number for the first time, with a ratio of 7 to 6, and indications expanded beyond oncology to include systemic lupus erythematosus, HPV infection, Parkinson's disease, stroke, liver failure, chronic hepatitis B, and other non-oncological conditions. Notably, most of the 93 projects are legacy filings carried over from previous regulatory frameworks. Only three were newly initiated and completed under the Decree 818 framework, representing an approval rate of less than 10%.
Industry experts point out that the new regulation does not lower the bar, it raises it, with only about 5% of companies estimated to possess full compliance capabilities. State-owned enterprises are accelerating their entry into the cell and gene therapy space, and total cross-border partnerships and out-licensing deals in the sector have surpassed $40 billion. The technology landscape is diversifying, with differentiated directions such as autoimmune and neurodegenerative diseases gaining momentum. The Guidelines for Confirmatory Clinical Studies of Biomedical New Technologies (Version 1), released in July 2026, set clear standards for confirmatory studies, signaling steady progress in industrial quality and innovation capacity.
A Milestone Does Not Mean Perfection
Yet exploration of any frontier science and advanced therapy comes with costs. Just ten days after the FDA approved the IND, overseas media disclosed a serious adverse event in the RXIM002 IIT study: a patient in her 50s with systemic sclerosis passed away after receiving the investigational product. This marks the third reported SAE involving a Chinese IIT subject in recent months.
Dr. Zhang Dan, founder, chairman, and CEO of Fountain Medical Development, told PharmaDJ theses issues arising during the development and maturation of advanced therapies are a global phenomenon, not unique to China. He cited the example of Professor Jim Wilson's team at the University of Pennsylvania in 1999, which experienced a gene therapy-related death that prompted a major NIH investigation and a temporary suspension of the university's entire gene therapy program, which was only gradually restored years later. "This shows that science progress has always moved forward through trial and error and the accumulation of knowledge," he said.
Zhang further noted that, at the scientific level, frontier therapies such as gene editing and in vivo CAR-T carry substantial scientific unknowns. Risks associated with delivery system immunogenicity, off-target effects, and cytokine release syndrome remain common challenges faced by the global scientific community.At the operational level, clinical trials for cell and gene therapy products, whether conducted as registration studies or IITs, face a series of systemic challenges far beyond those of traditional small molecules or antibody drugs.
"Cell and gene therapy products are often individualized, live-cell, or viral-vector-based preparations. Their manufacturing processes are complex, batch-to-batch variability is high, cold-chain transport requirements are extremely stringent, and the time window from collection to manufacturing to infusion is exceedingly narrow. These factors impose demands on clinical site infrastructure, operational procedures, and staff training that far exceed those of conventional drug trials," Zhang explained.
In addition, gene-edited and cell-based products may exert sustained biological effects, potentially persisting for a lifetime, once administered. "This means the monitoring window for serious adverse events is not limited to weeks or months after dosing but may extend to years or even decades of follow-up. Establishing sustainable long-term patient follow-up mechanisms in clinical trials is a real-world challenge faced globally," he added.
With respect to regulatory reporting, fulfilling notification obligations to the FDA, NMPA, and the National Health Commission is standard practice in scientific exploration and clinical development. However, it is important to clarify that the reporting responsibilities differ by study type: in registration studies, the company, as sponsor, bears direct responsibility for transparent disclosure to regulators; in investigator-initiated trials, the initiating entity is the hospital or investigator, with the company participating as a collaborator, and reporting obligations to the National Health Commission rest with the initiating institution.
Yet the occurrence of three serious adverse events in succession raises a fundamental question: when industry enthusiasm is high and pipelines are accelerating, is investigator responsibility for subject safety always being prioritized?
Some industry experts have pointed out that certain cases have exposed gaps such as "tight front-end, loose back-end" ethical review and insufficiently rigorous patient enrollment screening. Kang Wei, founder of the Guangdong-Hong Kong-Macao Biomedical Innovation Federation, recently raised a thought-provoking question at the 2026 Biomedical New Technology Clinical Research and Translational Application Exchange Conference: "If a patient is willing to assume the risk, does that alone make the risk ethically acceptable? Where is the boundary for hospitals and ethics committees in making that judgment?"
Other experts responded that ethical review should not be a one-time gatekeeping action but should encompass pre-assessment, informed communication, new safety signal reporting, and staged risk evaluation during long-term follow-up. For frontier technologies, exploration should not be halted due to risk, nor should scientific and ethical standards be lowered simply because patients are "willing to try".
Kang Wei further noted, "Technological innovation determines what can be done; product quality determines what can be done reliably; ethics helps us judge what should be done. But ultimately, CGT must come back to one question: is the patient safe? Innovation does not automatically equal translation. The journey from scientific feasibility to patient benefit requires scientific evidence, product quality, clinical risk assessment, and ethical judgment working together. The next phase for China's CGT sector is not just about more innovation. It is about quality capabilities, ethical governance, translational capacity, and cross-stakeholder coordination that can keep pace with the speed of innovation."
Chinese IITs: Achievements and Exposed Gaps
The implementation of Decree No. 818 marks a new, regulated phase for Chinese IITs at the institutional level. But regulation is only the first step. Harder challenges lie ahead: ensuring ethical review is embedded throughout the research lifecycle, ensuring investigators truly uphold the primacy of subject welfare, and ensuring patients genuinely understand the risk boundaries of frontier therapies.
Zhang Dan believes that Decree No. 818 was introduced to bring greater standardization to China's IITs, so the field can develop steadily and sustainably, with stronger SAE management, and more robust scientific and ethical safeguards. The dual-review mechanism introduced by the decree, involving both academic and ethics committees, further strengthens subject protection and brings more rigor and scientific discipline to research activities.
Notably, most of the issues recently reported in the media occurred last year or prior to the implementation of Decree No. 818. Their emergence, in a way, validates the necessity and timeliness of the new regulatory framework.
"China, as a global leader in cell and gene therapy, is already putting patient-first values and subject protection into practice," Zhang Dan told PharmaDJ. "And through our clinical experience here, we are ultimately benefiting patients worldwide. That is why, in revealing these issues, we should come together across borders to build better global governance and consensus in advanced therapies like cell and gene therapy. The goal is to ensure that lessons learned in one country can benefit the entire world. The ultimate objective remains unchanged: to address unmet medical needs globally."
Li Xiaokun, academician of the Chinese Academy of Engineering, stated at the Biomedical New Technology Clinical Research and Translational Application Exchange Conference: "Enthusiasm is high, but project approval is only the first step. How to implement and conduct clinical trials and translation with quality and in accordance with standards is what industry practitioners must diligently address going forward." Wu Yupu, professor at the Chinese Medical Association, remarked: "China's cell and gene therapy industry has persevered under extraordinarily difficult history to reach where it is today. Now is the time to seize the opportunity and strengthen the sector."
As noted at the outset of this article, the FDA's IND approval based on Chinese IIT data is a global-level recognition of China's clinical research capabilities. This acknowledgment has not come easily and deserves to be cherished by the entire industry.
Song Ruilin, senior president and chief expert of the China Pharmaceutical Innovation and Research Development Association(PhIRDA), concluded: "These safety incidents in China remind the gene cell therapy industry that while we are pursuing Global Firsts, we must always reflect and never relax our commitment to quality and safety. Only then can Chinese IITs genuinely earn long-term global trust and respects and allow more patients to benefit from innovative therapies. And that is the original aspiration of all IIT exploration."
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Chinese Experts Weigh In on Three Serious Adverse Events in Cell and Gene Therapy Trials
·08/20/2026