The field of genetic therapies needs robust investments, transparency and reliable regulatory frameworks to overcome recent challenges and continue to translate new technologies into patients’ benefit.
More than 50 gene therapies have now received approval globally with many more products nearing registration. Notably, the first personalized gene-editing therapy was developed in record time to save the life of a newborn1 with a severe metabolic disorder, and the first clinical report2 of prime editing in two patients with immunodeficiency has been published.
Despite these successes, 2025 was a challenging year for the field of gene therapy. The most recent global landscape analysis3 from the American Society for Gene & Cell Therapies paints a contrasting picture on the health of the field. It reports that although more gene therapies have progressed to advanced late-stage clinical trials, the total number of drugs in active development declined in 2025, marking a reversal from the upward trend observed in previous years. The analysis suggests that this trend is driven by a shift away from preclinical research programs, as well as the restructuring of early phase clinical pipelines, that saw several biotech and pharmaceutical companies terminating research tracks and proceeding with mass layoffs.
These dynamics probably reflect the challenges that the field has recently encountered. Concerns about the safety of genetic therapies have resurfaced in the past year, following the death of patients after receiving gene therapy for Duchenne muscular dystrophy and a CRISPR gene-edited product for amyloidosis. Consequently, several trials were put on temporary clinical hold in 2025. At the same time, the high manufacturing costs and low adoption rates have led to the discontinuation of a gene therapy for hemophilia B, less than a year after it was approved.
Although the field of genetic therapies has weathered cycles of setbacks and hype in the past, the chaotic regulatory landscape of the past year in the USA has not helped. The rates4 of clinical development success and approval have been historically higher for genetic therapies than for any other type of therapy. However, the past 12 months have seen an unusually high number of genetic therapies failing to secure approvals by the Food and Drug Administration (FDA). This included gene therapies for Huntington’s disease5 and for Hunter syndromedespite the companies developing these products previously receiving encouraging feedback by the agency on their clinical trial data.
The global regulatory landscape is also changing quickly. At the end of 2025, the FDA announced new guidance for the approval of cell and gene therapies, and a roadmap6 delineating for the first time a potential approval path for personalized gene-editing therapies. These new guidelines are expected to introduce greater flexibility by generally lowering data requirements for approval. However, some critics caution that this approach could increase potential risks for some patients. These contrast with the more cautious stance of the European Medicines Agency, which relies on conditional approval pathways. China, by contrast, is at the forefront of new technological development, but it has so far lagged in terms of products reaching the market. In addition to nine chimeric antigen receptor (CAR) T cell products, only one gene therapy, for hemophilia B, is currently approved. This situation is expected to shift with the implementation of new National Medical Products Administration guidelines, set to take effect in spring 2026. These measures are designed to streamline the review and approval process for innovative drugs, accelerate sector growth, and encourage greater investments.
Although the current climate remains uncertain, reducing investments in preclinical programs can have long-lasting negative consequences. The genetic therapy field relies heavily on the development of new technologies, from the generation of new vectors and methods to limit off-target effects, to new delivery approaches. It is also a field that moves new technologies remarkably quickly into the clinic, with prime editing taking only 5 years from preclinical development to clinical trials, and in vivo gene therapies and CAR T cell products reaching the clinic thanks to new delivery methods. As new technologies are often developed in academic settings, new frameworks for academic–industry collaborations are also emerging. A first for the field was the FDA approval of the first gene therapy7 developed by a non-profit organization through collaborations with academic groups.
At the same time, given the efforts and costs involved in conducting clinical studies in genetic therapies, it is essential that all the data generated are shared with the community, including those from trials that are terminated early as part of strategic restructuring or owing to a lack of efficacy. First-in-human trials are centered on the identification of safety signals, and the transparent and timely reporting of these is particularly important in this field, given the continuing concerns about the safety of gene therapies. Many trials that are terminated early, however, are not reported, and detailed data are often not shared beyond regulatory reporting and press releases. This is a lost opportunity to protect patients and to inform gene therapy development, and new approaches for the standardized reporting of safety signals of gene therapies are urgently needed.
Genetic therapies have the potential to provide one-off curative treatments for many patients with severe diseases. To fully realize its promise, the field needs to be supported by continued investments and robust and predictable regulatory pathways, and different contributors need to engage in a transparent and collaborative way, or it risks losing its momentum.