China’s hospital-led cell and gene therapy sector expanded rapidly after 2015. A 2025 analysis in Clinical and Translational Science found that investigator-initiated trials, or IITs, registered on ClinicalTrials.gov reached 207 in 2023, 11.2 times the 2015 figure. The researchers identified 1,033 qualifying trials involving more than 30,000 participants across the full dataset.
These studies operated through China’s therapeutic research track, overseen primarily through hospitals and the National Health Commission rather than the National Medical Products Administration’s drug-registration process. That rapid growth preceded State Council Order No. 818, which was issued in September 2025 and took effect on 1 May 2026.
What an IIT actually is
An investigator-initiated trial is designed and led by a clinician, hospital, or academic investigator rather than being structured as a company-sponsored registration trial. In China’s dual-track system, an IIT can proceed through institutional scientific and ethics review without first obtaining NMPA investigational-drug clearance. The resulting evidence can inform later development, but it does not replace the formal drug-registration pathway.
The model can provide early proof of concept for rare diseases and experimental therapies that might struggle to attract a conventional sponsor. It also places substantial responsibility on the hospital’s review, monitoring, consent, and reporting systems.
The curve from 2015 to 2023
The 2025 analysis began with 1,196 China-based cell and gene therapy records from ClinicalTrials.gov and excluded 163 domestic trials identified as formal investigational-drug studies. Its final set contained 1,033 IITs, including 929 single-centre studies. Gene-modified cell therapies represented more than half of the annual IIT total throughout the period beginning in 2015.
Shanghai and Beijing were the two largest individual hubs, accounting for 15.9% and 14.1% of the trials respectively. A separate 2025 Frontiers in Medicine analysis identified a rapid-growth phase in Chinese clinical-trial quality-management research from 2011 to 2024, with publication peaks in 2015 and 2022.
The expansion also attracted substantial capital to gene-modulation companies. In September 2025, Shanghai-based Epigenic Therapeutics announced a $60 million Series B to advance EPI-003 for chronic hepatitis B and EPI-001 for hypercholesterolaemia. That financing demonstrates investor interest in the field, although the announcement does not establish that China’s IIT rules were the reason for the investment.
The two deaths that intensified scrutiny
On 8 September 2026, Nature reported that two children had died in separate Chinese gene-editing trials, raising questions about oversight and disclosure. Both deaths occurred in 2025 but became public during the summer of 2026.
In the first case, a six-year-old girl with Snijders Blok-Campeau syndrome received an experimental CRISPR base-editing treatment at Xinhua Hospital in Shanghai in March 2025. The Straits Times, citing the joint Science and Retraction Watch investigation, reported that she died days later after a severe immune reaction. The work was led by neuroscientist Qiu Zilong of Shanghai Jiao Tong University School of Medicine, with physician Yongguo Yu overseeing the study.
Reports on the preclinical work raised further concerns. According to BioNews, published by the Progress Educational Trust, all four macaques in the final toxicology study developed liver damage, while one high-dose animal also developed kidney damage. Those results were not disclosed in the subsequently published animal paper.
The second case involved HG302, HuidaGene Therapeutics’ experimental CRISPR therapy for Duchenne muscular dystrophy. In an August 2026 statement, HuidaGene said a participant in the high-dose cohort died in August 2025 after developing acute respiratory distress syndrome amid severe complement and cytokine activation following systemic AAV administration. The company said the event had been reported through the hospital’s ethics and oversight processes within the applicable timeframe.
HuidaGene also said it submitted its findings for peer review in January 2026, seven months before publicly disclosing the death. According to the company, the other three participants did not develop the same severe syndrome and remain under long-term follow-up.
The missing independent board
A data monitoring committee, also called a data safety monitoring board, is an independent group that reviews accumulating safety and efficacy information and can recommend changes or termination. TechTimes reported that HG302’s public registry record listed no data monitoring committee. The absence of a listed committee meant no independent monitoring board was identified publicly as reviewing the trial’s dose escalation, although the available record does not establish what internal safety review occurred.
AAV vectors are widely used to carry genetic material into human cells, but high systemic doses can provoke serious immune reactions. The risk is documented in the same disease area: in November 2025, the US Food and Drug Administration added a boxed warning to Elevidys following two fatal cases of acute liver failure in non-ambulatory paediatric patients with Duchenne muscular dystrophy.
Elevidys and HG302 are different products, so the Elevidys cases do not establish what happened in the HG302 trial. They do show that severe immune and liver complications from systemic AAV treatment were known risks before HuidaGene disclosed the participant’s death.
What Order 818 changes
The official bilingual text of Order No. 818 records an issue date of 28 September 2025 and an effective date of 1 May 2026. It limits qualifying research institutions to Class A tertiary hospitals, requires both academic and ethics review, and requires studies to be filed with the national health authority within five working days of approval. It also requires a study to be suspended after a severe adverse reaction while the ethics committee evaluates whether it can continue.
The regulation requires that the decision to resume or terminate such a study be reported within five working days. The text does not expressly make an independent data monitoring committee mandatory or state that its requirements apply retroactively to trials begun before 1 May 2026.
The institutional stakes
Joy Zhang, a University of Kent sociology professor who studies the governance of scientific risk, told CNN that the Xinhua case was especially concerning because it involved established scientists at a prestigious institution. She contrasted that institutional setting with the 2018 case of He Jiankui and questioned why repeated government commitments to strengthen research ethics had not prevented the failures described in the investigation.
Shi Jiayou, a professor at Renmin University of China Law School, argued that participant safety must take priority over prestige and claims of scientific priority. China Daily reported that Shi viewed the exposure of a child with a non-life-threatening condition to known lethal risks as inconsistent with China’s ethical-review principles.
The Gelsinger parallel
The cases have prompted comparisons with Jesse Gelsinger, an 18-year-old who died in 1999 after a severe immune reaction during a Phase I gene-therapy trial for ornithine transcarbamylase deficiency. A National Academies workshop summary described the case as a lasting lesson about eligibility criteria, informed consent, transparency, conflicts of interest, and institutional oversight. It also linked the case to later efforts to strengthen regulatory safeguards.
The biological circumstances were not identical because Gelsinger received an adenoviral vector, while the two Chinese trials used AAV delivery. The meaningful parallel concerns governance: warning signals, independent review, informed consent, adverse-event reporting, and the consequences of delayed disclosure.
What the HG302 registry shows
After the HG302 participant died in August 2025, the study remained listed as recruiting for roughly six months. On 13 February 2026, the record was changed to completed, planned enrolment was reduced from six to four, and 2 December 2025 was entered as the completion date. On 31 July 2026, the status was changed again to active, not recruiting, with the final completion date extended to June 2027.
The surviving participants’ follow-up period was extended from 26 to 104 weeks. The registry history does not explain the sequence, and the timing alone should not be treated as proof of concealment or motive.
A pathway under a harder test
The registry data establish that China’s cell and gene therapy IIT sector grew rapidly, reaching 207 new trial registrations in 2023 and more than 30,000 participants across the study’s full dataset. That expansion produced early clinical evidence and development opportunities, but it also increased the number of patients relying on institutional safeguards outside the NMPA registration pathway. The two deaths do not establish that IITs as a category are unsafe, but they show how consequential gaps in monitoring and disclosure can become.
Order 818 creates clearer national requirements for review, filing, suspension, reporting, and long-term follow-up. Its significance will ultimately depend on whether those provisions produce timely scrutiny and transparent responses when serious adverse events occur.
