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CME Evaluation

Oral Communication Session

Inherited Bleeding Disorders and Inhibitors

Session: Gene therapy - Long term follow up

OC 30.4 - Sustained efficacy of gene transfer with BBM-H901 in Chinese Hemophilia B patients: results of long term follow up

Monday, June 24, 2024
10:15 – 10:30 ICT
Room: Plenary Hall

    Presenting Author(s)

  • Feng Xue, MD

    Chief physician
    State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China
    Tianjin, Tianjin, China (People's Republic)

    • Co-Author(s)

  • xw

    xia wu

    Professor
    Belief BioMed, Xuhui District, Shanghai, China
    Shanghai, Shanghai, China (People's Republic)

  • xx

    xiao xiao

    Professor
    Belief BioMed, Xuhui District, Shanghai, China
    Shanghai, Shanghai, China (People's Republic)

  • LZ

    Lei Zhang

    professor
    State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China
    Tianjin, Tianjin, China (People's Republic)

Background: BBM-H901 is a novel vector comprised of liver-trophic AAV843 and a cassette expressing a hyperactive Padua factor IX (FIX) protein. In 2019 we started a single-center, single-arm, pilot trial evaluating the safety and efficacy of a single intravenous infusion of BBM-H901 in 10 Chinese hemophilia B patients. The study was approved by ethics committees of Blood diseases hospital, CAMS.

Aims: To present long-term safety, FIX coagulation activity (FIX:C) and bleeding events for patients treated with BBM-H901.

Methods: Ten hemophilia B patients (FIX≤2% and aged≥18) was successfully enrolled and dosed with a single infusion of BBM-H901(5E12 vg/kg) from October 2019 to January 2021. To prevent vector-related immune response, a tapering course of corticosteroids was administered before and after BBM-H901. Factor IX activity (FIX:C) and adverse events was evaluated regularly per protocol.

Results: Ten patients were follow-up for a median 130 weeks (Range 130 to 209 weeks). At all patients’ latest follow-up, the mean(±SD) FIX:C level was 38.36(±19.89)% measured by one stage APTT based method using Dade Actin FSL（Siemens， Germany） reagents. The mean FIX:C level at each time points maintain stable expression after BBM-H901 treatment (Figure).
One patient had an aggravation of a previous hematoma after intensive activities and intermittently used FIX concentrate 10 times after 19 weeks, another patient lost transgene expression after 130 weeks ( FIX:C＜5%) and had 2 times of joint bleed episode which needed to be treated, the other eight patients had no bleeding events. The transgene derived FIX:C enabled the termination of baseline replacement therapy in in 9/10 patients (Table).
There were no deaths, SAEs associated with BBM-H901, thrombotic event, or FIX inhibitors.

Conclusion(s): This study suggests that BBM-H901 is safe more than 2.5 years after infusion. Vector derived FIX:C level is sufficiently high to prevent bleeding events and minimize the need for replacement therapy in HB patients.