Hemophilia B is an inherited bleeding disorder caused by mutations in the F9 gene, which encodes coagulation factor IX (FIX). Gene therapy, which restores the production of functional FIX by delivering a functional F9 gene, is currently the only potentially curative approach for hemophilia B. Gene therapy products that use liver-targeted adeno-associated virus (AAV) vectors to deliver a highly active FIX variant, FIX-Padua, have demonstrated promising efficacy in clinical trials. To date, two such products have been approved internationally [1–2]. Among them, BBM-H901 (DalnacogenePonparvovec), developed by Professor Xiao Xiao’s team at Belief BioMed, is the first AAV-based gene therapy product for hemophilia B developed in Asia.In 2019, Professor Lei Zhang’s team at our hospital conducted the first clinical study of BBM-H901 in patients with hemophilia B, providing preliminary evidence of its efficacy and safety in Chinese patients. The findings were published in The Lancet Haematology in July 2022 [2]. Subsequent Phase 1/2 and Phase 3 clinical trials further confirmed the favorable efficacy and safety profile of BBM-H901. The results were published in Nature Medicine in January 2026 and contributed to its approval by the National Medical Products Administration (NMPA) of China in April 2025. BBM-H901 thus became the first gene therapy for hemophilia approved in China, indicated for prophylactic treatment of adults with hemophilia B [3].However, until now, no clinical data on gene therapy for hemophilia B in patients younger than 18 years of age had been reported internationally. An important question therefore remained: Can children and adolescents with hemophilia B safely receive gene therapy?

On September 16, 2026, the collaborative team led by Professor Lei Zhang and Professor Renchi Yang from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences; the team led by Professor Qun Hu from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; and Professor Xiao Xiao’s team from Belief BioMed published online in Nature Medicine (IF = 52.5) the results of a Phase 1 clinical trial entitled “Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial.”This study provides the first preliminary evidence that BBM-H901 is safe and effective in adolescents with hemophilia B. The therapy rapidly increased FIX activity and substantially reduced the annualized bleeding rate (ABR), providing clinical evidence to support the use of gene therapy in children and adolescents with hemophilia B.

This was a multicenter, single-arm, open-label clinical trial that enrolled 11 participants. Three participants were aged 16–17 years, four were aged 14–15 years, and four were aged 12–13 years. All participants received BBM-H901 at a dose of 5 × 10¹² vector genomes (vg)/kg. The primary objectives were to evaluate the safety and efficacy of the treatment.

Participants were enrolled sequentially from the oldest to the youngest age group. The results demonstrated a favorable safety profile. One serious adverse event (SAE) and two Grade 3 adverse events were reported, none of which were considered related to the investigational treatment. No factor IX inhibitors or thrombotic events occurred. The most common adverse events included increased white blood cell counts, increased neutrophil counts, and rash, all of which were associated with corticosteroid use. One participant developed abnormal liver function, which resolved after intensified immunosuppression and hepatoprotective treatment.

In terms of efficacy, at Week 52 after gene therapy, the mean FIX:C level was 41.8 (SD 30.1) IU/dL, as measured using the one-stage clotting assay. Notably, mean FIX:C reached a peak of 67.1 (SD 23.1) IU/dL as early as Day 6 after gene therapy, enabling patients to rapidly discontinue replacement therapy.The annualized bleeding rate (ABR) was 0.50 (95% CI, 0.1–2.9), representing a marked reduction from 13.9 (95% CI, 0.6–27.2) before treatment. The mean annual number of infusions of factor IX products decreased from 77.7 (SD 32.0) before treatment to 1.45 (SD 2.46) after treatment. The frequency of joint bleeding was also substantially reduced, and the number of target joints decreased to zero.

This study represents the first clinical trial of gene therapy for hemophilia B in adolescents internationally, demonstrating that gene therapy with the highly active FIX-Padua variant is safe and effective in Chinese adolescent patients. The therapy showed a rapid onset of action, allowing patients to benefit quickly from gene therapy and potentially expanding the population eligible for gene therapy for hemophilia B.

Professor Lei Zhang, Professor Renchi Yang, Professor Qun Hu, and Professor Xiao Xiao are co-corresponding authors of the study. Professor Feng Xue, Dr. MankaiJu, Dr. Ai Zhang, Professor Xia Wu, and Assistant Researcher Bingqi Xu are co-first authors.The study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Tianjin Municipal Science and Technology Commission Grant, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the China Higher Education Institution Industry-University-ResearchInnovation Fund, and the Fundamental andInterdisciplinary Disciplines Breakthrough Plan of the Ministry ofEducation of China.

Link:https://www.nature.com/articles/s41591-026-04636-8