After 2 undisclosed gene therapy deaths, can China’s alternative regulatory path still be trusted?

Brought to you by: Biotech After 2 undisclosed gene therapy deaths, can China’s alternative regulatory path still be trusted? By Angus Liu, Darren Incorvaia Aug 17, 2026 7:20am China Cell & Gene Therapy drug safety clinical trial Amid growing U.S. anxiety over China’s rapid rise as a biotech powerhouse, a fast regulatory pathway for early development of novel cell and gene therapies has become a recent focal point.

Through investigator-initiated trials (IITs), Chinese academics and hospitals can launch early-stage, in-human studies faster with fewer requirements than the standard drug review process permits in both the U.S. and China. But two undisclosed deaths tied to gene-therapy IIT studies have raised questions about the role of this pathway.

In the first case, reported by the jornal Science along with the blog Retraction Watch, a 6-year-old girl with a rare—but nonfatal—neurodevelopmental disorder died last year from a severe immune response just days after receiving an experimental base-editing therapy funded in part by her parents. In the second case, uncovered by Stat, a young boy enrolled in HuidaGene Therapeutics’ IIT trial for Duchenne muscular dystrophy died last year of acute respiratory distress syndrome following administration of a CRISPR-based treatment. Together, the two incidents—both involving severe immune reactions to high-dose, viral vector-delivered gene therapies and a lack of disclosures—have drawn international scrutiny to what appear to be systemic gaps in oversight and transparency within China’s IIT framework.

The significant delay in public disclosures raised concerns about similar underreported deaths and other severe adverse events. But experts familiar with China’s drug regulatory system argue that fixating on those cases and deeming IIT unreliable would be ignoring new guardrails that the Chinese government has since put in place. “From a legal perspective, in the biopharma sector, we believe this incident will not fundamentally dampen China’s domestic enthusiasm for conducting IIT trials,” Aaron Gu, a partner at Chinese law firm Han Kun who specializes in healthcare and life sciences, said in an email interview with Fierce following Science’s first report.

Compared with investigational new drug (IND) clinical trials aimed at regulatory registration, the core value of IITs remains unchanged, Gu noted, and so does the industry’s demand for faster generation of high-quality, early proof-of-concept clinical data to support R&D decision-making. Gu’s confidence is built on a new regulation that China’s central government issued in October 2025 and officially went into force in May 2026, after the two reported deaths had happened but before they were made public. Known as Order 818, the regulation established more standardized frameworks and tighter requirements for conducting IITs, with specifications through a series of guidelines covering trial protocol design, preclinical safety evaluation, risk management and control, subject screening and drug product quality requirements, Gu observed.

Nevertheless, the high-profile media reports and implementation of new regulations are expected to slow down IITs for a while, and the pathway’s damaged reputation could take time to heal. It wasn’t long ago that scientists and regulators alike in the U.S. were singing the praises of China’s speedy IIT system, with some calling for the FDA to emulate it.

At an FDA cell and gene therapy roundtable in June 2025, CAR-T pioneer Carl June, M.D., encouraged the agency to adopt China’s two-tiered model and allow researchers in the U.S. to more easily launch first-in-human trials. “Why are researchers increasingly taking trials overseas?” June asked at the time.

“Simply put, the U.S. process has become too slow, costly and inflexible, while other countries make it easier to innovate.” June declined to comment for this story. Roughly a year later and on the heels of significant leadership turnover at the FDA, the Department of Health and Human Services announced a comprehensive plan that it claimed will speed up phase 1 trials in the U.S.

to just six to nine months. Part of the plan includes efforts to reshape requirements for institutional review boards to approve trial designs, though specific details are still scarce. According to Science's reporting on the first of the deaths, the ethics committee of Xinhua Hospital affiliated with the Shanghai Jiao Tong University School of Medicine did not review a critical primate safety study before greenlighting the trial.

The monkey study flagged serious liver toxicities, a common result of immune reaction to high-dose delivery of adeno-associated virus (AAV) gene therapy. Gu noted that prior to Order 818, there were no regulatory requirements regarding animal model selection for preclinical studies supporting IITs. Alongside the new decree, IIT filing guidelines now “explicitly mandate that non-clinical toxicology studies for new gene therapies must utilize ‘large animal’ models, including non-human primates like monkeys or other large animals,” he said.

Before Order 818, “the quality of preclinical package supporting IIT varie[d],” Steve Yang, chief financial officer at Merit and a co-founder of private equity firm Mianus Capital, told Fierce in an interview. “This is exactly what 818 is trying to enforce—a more consistent and higher standard.” Merit is a U.S.-based endpoint service CRO that has been operating in China since 2019. The company has been supporting a cell therapy IIT program in Shanghai for more than a year.

As Yang observed, many Western companies tapping into China’s IIT system already hold themselves to a high standard. “A lot of companies we’re dealing with already have a very comprehensive preclinical package,” Yang said. “They are already ready to submit to the FDA, and the reason they come to China is not because they want to circumvent any regulation.

Their objective is very simple: If I do it in the U.S., it’s going to take a year [or] six months to enroll the first patients. China is quicker.” The two fatal incidents notwithstanding, biopharma sponsors show no sign of pulling back from Chinese IITs. During an investor call on Aug.

11, Legend Biotech announced that the company plans to launch an IIT study in China to evaluate its BCMA-targeted in vivo CAR-T cell therapy, LB2505, for multiple myeloma, as a continuation of its collaboration with Johnson & Johnson. Back in June, Legend reported promising first-in-human data from its dual CD19/CD20-targeting in vivo CAR-T candidate, LB2501, from a China IIT study showing 100% response rate among six B-cell non-Hodgkin lymphoma patients, with no serious adverse events reported. “We believe the China IIT model is very robust and very helpful in getting early proof of concept, and we obviously work very closely with the China regulatory authorities, as well as all the investigators, to make sure that we have the highest standards of quality in our programs,” Legend’s interim CEO, Alan Bash, said in an interview with Fierce.

Han Kun’s Gu also figured that an “isolated incident won’t erase international confidence in China’s overall IIT data,” especially as Order 818 standardizes the practice. “Both medical institutions and biotech/pharma sponsors are adopting near-IND standards to strictly control IIT quality, providing even firmer assurances for the authenticity and integrity of Chinese IIT data,” he said. While Yang sees no change of heart from drug developers, he does expect the two deaths and the new regulation to slow China IITs in the near term with more uncertainties down the road.

“Everyone will be more vigilant, which means it will definitely slow down a little bit,” he said. First, Merit has already received feedback that several Chinese hospitals are halting their IIT programs while they figure out how to navigate the new regulations. Just as hospitals need time to digest the rules, government agencies must hire additional staff to process the workload.

Alongside hospital-level ethics and academic reviews, Order 818 added a filing review procedure under the National Health Commission, Gu noted. “You can’t just turn on the switch on May 1 because the infrastructure is not there,” Yang said. Even though the filing process does not require a government “approval” per se, Yang expects officials to conduct rigorous reviews of IIT filings before acceptance to ensure they follow the updated policy.

Fears have also emerged that the reports of the two deaths and the accompanying public scrutiny could deter researchers and hospitals from running IITs for potentially life-saving medicines, just like how the death of Jesse Gelsinger in 1999 set back the entire gene therapy field. At 18, Gelsinger received an experimental gene therapy to treat his rare metabolic disease; he died four days later due to a severe immune reaction to the viral vector. Following Science’s report in July, six families of children with rare genetic diseases published an open letter pleading with the public not to shutter research into orphan conditions.

The authors were then flooded with abusive attacks online accusing them of making excuses for wrongdoings, according to China newspaper Southern Weekly (Chinese). In addition to the existing cell therapy program, Merit is helping a client set up an IIT in China for an AAV gene therapy candidate against an ultra-rare disease. As of the week ended Aug.

9, the principal investigator at a Shanghai hospital still suggested that the program is ready to be submitted for approval by the hospital’s ethics committee. However, Yang is warning the client of a potential delay. Discussions about harmonizing ethics committee review standards and IIT filing processes through one regional committee have been ongoing among government bodies in the Yangtze Delta, according to Yang.

The economic region is home to some of China’s busiest biopharma hubs such as Shanghai, Hangzhou and Suzhou. Hospitals in the region may want to wait for input from this filing committee before signing off on a new IIT program, he said. Sufficient animal studies mark just one of several safeguards that Order 818 has put around IIT.

To Yang, the timing of the new policy indicates that the Chinese government had likely received additional serious adverse event reports to the two deaths that came to light; after all, the two incidents involved top-tier hospitals, while other facilities with less expertise in cell and gene therapy were allowed to run IITs prior to Order 818. “I’ve been concerned all along that adverse events weren’t being disclosed, which made it harder to place any positive data that were reported into context,” Kiran Musunuru, M.D., Ph.D., a leader in personalized gene editing at the Children’s Hospital of Philadelphia and co-founder of Verve Therapeutics, told Fierce. No detailed analyses of the two deaths have been presented.

As Stat’s report noted, the purity of the viral vector can also affect safety, potentially triggering dangerous immune responses. Previously, EsoBiotec’s BCMA-targeted, lentiviral vector-based in vivo CAR-T candidate, ESO-T01, led to four cases of the immune side effect cytokine release syndrome, including three reaching grade 3, in a China IIT trial that enrolled five patients. An immediate inflammatory surge after infusion raised the possibility of insufficient vector purification, which could have been avoided under a more robust manufacturing standard.

In a statement to Fierce, a spokesperson for AstraZeneca, which bought EsoBiotec in 2025 for $425 million upfront, noted that the IIT trial was conducted before its acquisition. “The ESO-T01 trials demonstrated that in vivo cell therapy is feasible without lymphodepletion of patients and demonstrated clinical responses, validating this off-the-shelf approach,” the spokesperson said. “AstraZeneca is now working to further develop in vivo treatments based on these results.” Detailed requirements for drug production in gene therapy IITs were absent prior to Order 818.

The absence of this requirement versus an IND process played an important role in China IIT’s fast pace. However, that gap has been filled by the new regulation, Gu noted. Specifically, new filing guidelines for gene therapy IIT “explicitly mandate that the preparation of investigational products must fully comply with Good Manufacturing Practice (GMP) requirements across facilities, staffing, management systems and quality testing,” Gu said in a follow-up interview after Stat’s report of the HuidaGene case.

Deaths in gene therapy trials have been reported elsewhere. But in the two China IIT cases, the lack of public disclosure drew wide criticism. In Science’s report, researchers published preclinical findings in Nature in early 2026 without mentioning the 6-year-old.

In HuidaGene’s case, the company didn’t admit to the fatality until about a year later despite a monthslong media investigation and repeated queries. There are no regulations in China or globally requiring sponsors or medical institutions to immediately disclose serious adverse events to the general public. But withholding news of patient deaths in a field as delicate as gene editing could be viewed as a breach of public trust and a disservice to the broader scientific community.

Still, as Han Kun’s Gu noted, China’s current Good Clinical Practice guidelines are fully aligned with the international standards as outlined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Order 818 imposes even stricter trial suspension and reporting mechanisms for IITs, Gu said. If a serious adverse event occurs, the medical institution must pause the study without exception, as the ethics committee evaluates whether it may resume.

The research organization is also required to report to health authorities within five business days. “Those seem like positive developments,” said CHOP’s Musunuru. But “the devil is in the details,” and Musunuru suggested he is “not sure this goes nearly far enough” to address the incentive structure of the IIT mechanism.

This mechanism “offered domestic and international companies a way to play the lottery with Chinese patients’ lives,” he argued. To Yang, logistical delays to trial initiations and hesitations among some doctors are surmountable. The real concern lies in how drug regulators on both sides of the Pacific will act.

For Beijing, the alleged cover-up of the two deaths marked another public embarrassment following the 2018 scandal surrounding He Jiankui, whose rogue experiment to produce gene-edited babies sparked global outrage and forced Chinese authorities to crack down on such clinical research. “There’s a lot of people [who are] concerned about whether the government is going to apply a cookie-cutter solution and just stop everything,” Yang said about IIT in China. The Merit exec compared a full-on ban to “shooting your own foot,” arguing that the right approach would be to let Order 818 play out.

For Merit’s clients, the bigger concern would be how the FDA would respond. U.S. regulators have accepted China IIT data as supporting evidence to start clinical trials in the states.

American lawmakers have recently renewed their attack on clinical data from China. Rep. John Moolenaar (R-MI), chair of the U.S.

House Select Committee on China, sent letters to four Big Pharma companies in July outlining his concerns about their business dealings in the country. One issue he raised was the alleged connection between certain trial sites and the Chinese military. In his letter to Pfizer, Moolenaar argued that “data developed through clinical trials at those hospitals could fuel the [Chinese Communist Party’s] military biotechnology research, experimentation and capability development.” Back in 2024, Moolenaar, together with several other bipartisan lawmakers, had raised concerns about clinical trials conducted by major U.S.

biopharma companies alongside China’s military-affiliated hospitals and in Xinjiang. In May of this year, the House Appropriations Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies added language to a spending bill report seeking to ban data from China, Russia, Iran or North Korea from FDA consideration. That report advises the FDA on how to use its portion of the spending bill, which passed the House in June.

“Are they going to say, ‘Hey, this is what happened in China. China data cannot be trusted. China ethics standards are very low.’ It’s possible,” Yang said.

“Overall, I think this definitely creates more hurdle[s] for us as we are building this bridge to connect innovation with clinical research in China.” China Cell & Gene Therapy drug safety clinical trial adverse event reporting Adverse Events patient death CRO Research Biotech