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3582 Efficacy and Safety of an Engineered, Liver-Tropic Adeno-Associated Virus Vector Expressing Factor IX Padua Administered with Prophylactic Glucocorticoids in Patients with Hemophilia B: A Multi-Center, Single-Arm, Phase 3 Trial

Program: Oral and Poster Abstracts
Session: 801. Gene Therapies: Poster II
Hematology Disease Topics & Pathways:
Adult, Research, Clinical trials, Bleeding and Clotting, Clinical Research, Diseases, Adverse Events, Human, Study Population
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Feng Xue, MD1*, Mankai Ju2*, Tienan Zhu, MD, PhD3*, ZePing Zhou, MD, PhD4, Jing Sun5*, Linhua Yang6*, Zhenyu Yan7*, Hu Zhou8, Xin Du9*, Changcheng Zheng, MD10*, Xia Wu11*, Xiao Xiao12*, Renchi Yang, MD13,14 and Lei Zhang13

1Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China, Tianjin, China
2institute of haematology and blood diseases hospital, Chinese academy of medical sciences and peking union medical college, Tianjin, CHN
3Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, CHN
4Second Affiliated Hospital of Kunming Medical University, Kunming, China
5Nanfang Hospital Southern Medical University, Guangzhou, China
6The Second Hospital of Shanxi Medical University, Taiyuan, China
7North China University of Science and Technology Affiliated Hospital, Tangshan, China
8Department of Hematology, Henan Provincial Cancer Hospital, Zhengzhou, China
9Department of Hematology, The Second People's Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
10Anhui provincial hospital, Hefei, China
11East China University of Science and Technology, shanghai, China
12Belief BioMed, shanghai, China
13Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
14Institute of Hematology & Blood Disease, Tianjin, China

Introduction

Gene therapy is the cutting- edge treatment for hemophilia B. We launched the Phase 3 clinical trial of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX (FIX) protein (BBM-H901) to evaluate its efficacy and safety in adult patients with hemophilia B.

Methods

A multi-center, single-arm, phase 3 trial was launched to evaluate the efficacy and safety of a single intravenous infusion of BBM-H901. The main inclusion criteria is adult patients with hemophilia B (aged≥18 years) with baseline FIX coagulation activity (FIX:C) of ≤2 IU/dL, no FIX inhibitor, and neutralizing antibodies against vector capsid ≤1:4. Eligible participants were intravenously infused with a single dose of 5 × 10¹² vector genomes (vg)/kg of BBM-H901 after 1 day of prophylactic oral prednisone at 1 mg/kg/d. The initial dose (1 mg/kg/d) lasted 2 weeks after vector infusion and tapered off in around 8-10 weeks. The primary endpoint is ABR (annualized bleeding rate), within 52 weeks after BBM-H901 injection infusion. We report the results of the prespecified 1-year analysis following complete enrolment. The trial is registered with ClinicalTrials.gov, NCT05203679.

Results

Between Aug 17, 2022, and Apr 21, 2023, 28 male participants were assessed, and 26 Chinese participants were enrolled and administered with BBM-H901 via intravenous infusion. After 52 weeks follow-up, average ABR is 0.6 (95%Cl: 0.18-1.99) which significantly lower than superiority margin 5.0 (identified ABR of patient with prophylactic treatment in China). Mean FIX:C reached 55.08 IU/dL (SD35.93) measured with one- stage method using SynthASil aptt reagents at week 52. Furthermore, as early as 3 days after infusion, mean FIX:C reached 49.70 IU/dL very quickly. The average number of FIX product infusion after BBM-H901 treatment is 2.9 (SD 10.71), lower than before 58.2 (SD 30.67). 21/26 participants had zero replacement therapy after gene therapy. The mean target joint number decreased from 1.1 (SD 1.2) to 0. No serious adverse events, no grade 3–4 BBM-H901 related adverse events were observed. Most common grade 1–2 adverse events related to BBM-H901 include elevation of alanine aminotransferase (7 [26.9%]), elevation of aspartate aminotransferase (2 [7.7%]), decrease of fibrinogen (3 [11.5%]). Factor IX inhibitors did not develop in any participants.

Conclusions

This phase 3 trial come up with the point that BBM-H901 can decrease the ABR compare to the prophylactic treatment, elevate FIX:C level sufficiently and rapidly to prevent bleeding events. Besides, the trial also supports the safety and tolerability.

In conclusion, BBM-H901 gene therapy is superior to prophylactic treatment with respect to the ABR, and it had a favorable safety profile.

Disclosures: Xiao: Belief BioMed: Current Employment.

*signifies non-member of ASH