VPB0208 - Coagulant potential of emicizumab in child hemophilia A patients

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Masahiro Takeyama, MD, PhD

Associate Professor
Nara Medical University
Kashihara, Nara, Japan

Co-Author(s)

Naoki Matsumoto, PhD

Researcher
Chugai Pharmaceutical Co., Ltd.
Kamakura, Kanagawa, Japan
HA

Hiroto Abe

Researcher
Chugai Pharmaceutical Co., Ltd.
Kamakura, Kanagawa, Japan
SH

Suguru Harada

Product Research Dept.
Chugai Pharmaceutical Co., Ltd.
Kamakura, Kanagawa, Japan
KO

Kenichi Ogiwara

Assistant professor
Department of Pediatrics, Nara Medical University
Kashihara, Nara, Japan
SF

Shoko Furukawa

Assistant professor
Department of Pediatrics, Nara Medical University
Kashihara, Nara, Japan
TS

Tetsuhiro Soeda

Researcher
Chugai Pharmaceutical Co., Ltd.
Kamakura, Kanagawa, Japan
KN

Keiji Nogami

Professor
Nara Medical University, Nara, Japan
Nara, Nara, Japan

Background: Emicizumab prophylaxis reduces bleedings in the patients with hemophilia A (PwHA). A clinical study (HAVEN 7) including PwHA without inhibitors up to 12 months of age is currently ongoing, but it is not yet clear whether emicizumab affects infant PwHA.

Aims: To examine the coagulation potential of emicizumab in vivo or ex vivo in plasma collected from 0 to 42-month-old child PwHA (child-HA).

Methods: This study was approved by two institutional review boards and informed consent was obtained. Plasma from 27 child-HA patients up to 42 months of age, receiving emicizumab, a factor (F) VIII agent, or neither emicizumab nor FVIII agent (median age; 19 months) were enrolled. FVIII activity in PwHA receiving FVIII agents was reduced to < 1 IU/dL by the addition of anti-FVIII A2 monoclonal antibody. Samples of emicizumab-spiked plasma (ex vivo) or emicizumab-treated plasma (in vivo) were analyzed. Untreated plasma or emicizumab-treated plasma supplemented with anti-emicizumab antibody were used as reference samples, respectively. Global coagulation activity was measured and adjusted for maximum coagulation velocity (Ad|min1|) in a clot waveform analysis (CWA) and peak thrombin was measured using thrombin generation assay (TGA).

Results: Ad|min1| in 24 of the 27 cases was improved in the presence of emicizumab. The 3 child-HA which did not respond were 1, 23, and 31 months of age. Although 20 of the 27 cases showed an age-dependent increase in peak thrombin with emicizumab, 7 cases (0, 1, 1, 2, 8, 19, and 36 months) did not. An emicizumab-dependent increase in coagulant potential was shown in 18 cases by both Ad|min1| and peak thrombin, and in 8 cases by one parameter but not the other. Only 1 case (1 month of age) did not respond with either Ad|min1| or peak thrombin.

Conclusion(s): In general, emicizumab improved coagulant potential in child hemophilia A plasma evaluated by global coagulation assays.