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1213 A Specific Coagulation Factor X Activator for on-Demand Treatment in Hemophilia with Inhibitors

Program: Oral and Poster Abstracts
Session: 322. Hemophilia A and B: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Wei Liu, MD1*, Hu Zhou2, Ruibin Huang, MD3*, Xin Du4*, ZePing Zhou, MD, PhD5, Changcheng Zheng, MD6*, Shifeng Lou, MD7*, Xinyue Dai, MD1*, Renchi Yang, MD1 and Lei Zhang1

1Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
2Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
3The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
4Department of Hematology, The Second People's Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
5Second Affiliated Hospital of Kunming Medical University, Kunming, China
6Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
7The second affiliated hospital of Chongqing Medical University, Chongqing, China

Background

Bemiltenase alfa targeting factor X (FX), purified from Daboia russelii siamensis venom, is developed as a hemostatic agent for hemophilia A or B with inhibitors (HAwI and HBwI).

Methods

This is a prospective, multicenter, open-label, phase Ib/II trial evaluating the safety and efficacy of bemiltenase alfa for on-demand treatment in HAwI and HBwI patients (Clinicaltrials.gov NCT05027230). Adults (18-65 years) male HAwI and HBwI patients were enrolled to achieve multiple doses of bemiltenase alfa in stage 1 (0.10 U/kg dose cohort) and stage 2 (0.10 U/kg cohort and 0.16 U/kg dose cohort). The primary endpoints were safety and hemostatic efficacy. The secondary endpoints were pharmacokinetic (PK) and pharmacodynamic (PD) profiles, alleviation of clinical symptoms of bleeding events, and the dosage of bemiltenase alfa needed to achieve hemostasis.

Results

Between October 2021 and July 2023, 80 patients were assessed for eligibility and 70 were enrolled. The 0.16 U/kg dose group (n=37) achieved an effective hemostasis rate of 96.48% (95% confidence interval: 92.89% to 98.57%) in 199 bleeding events, while the 0.10 U/kg dose group (n=20) showed a comparable rate of 94.07% (88.66% to 97.41%) in 135 bleeding events. The clinical remission rate also showed the same trend. For bleeding events, the 0.16 U/kg cohort required fewer number of injections (1.7±0.9 vs. 2.1±1.1, respectively P<0.001). Four patients in 0.16U/kg cohorts experienced grade one asymptomatic venous thromboembolisms. No drug-related serious adverse events or anti-drug antibodies were observed. PK findings showed that plasma drug concentrations increased with consecutive doses. The PD results indicated bemiltenase alfa can dramatically improve the activated partial thromboplastin time, peak height and endogenous thrombin-generating potential of thrombin generation assay.

Conclusion

Our study indicates that FX as a novel target in treating bleedings showed good efficacy. We also demonstrated for the first time that FX activator from snake venom showed good safety and strong therapeutic effect which supports its potential as a hemostatic treatment for HAwI and HBwI patients.

Disclosures: No relevant conflicts of interest to declare.

OffLabel Disclosure:

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