OC 40.2 - Efficacy, Safety, and Pharmacokinetics of Emicizumab Prophylaxis in Patients with Acquired Hemophilia A: Primary Analysis Results from a Phase III Study (AGEHA)

Monday, July 11, 2022

3:00 PM – 3:15 PM

Location: ExCel Center, ICC Auditorium

Presentation Format: Virtual

Presenting Author(s)

Midori Shima

Dean
Thrombosis and Hemostasis Research Center, Nara Medical University, Kashihara, Japan
Kashihara, Nara, Japan

Co-Author(s)

KA

Kagehiro Amano

Professor
Department of Laboratory Medicine, Tokyo Medical University
Tokyo, Tokyo, Japan
YO

Yoshiyuki Ogawa

Senior Assistant Professor
Department of Hematology, Gunma University Graduate School of Medicine, Maebashi, Japan
Maebashi, Gumma, Japan
Koichiro Yoneyama, MSc

Pharmaceutical Science Dept.
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Tokyo, Tokyo, Japan
RO

Ryoto Ozaki

Biometrics Dept.
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Tokyo, Tokyo, Japan
RK

Ryota Kobayashi

Specialty Clinical Development Dept.
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Tokyo, Tokyo, Japan
ES

Emiko Sakaida

Professor
Department of Hematology, Chiba University Hospital, Chiba, Japan
Tokyo, Tokyo, Japan
MS

Makoto Saito

Director
Blood Disorders Center, Aiiku Hospital, Sapporo, Japan
Sapporo, Hokkaido, Japan
TO

Takashi Okamura

Director
Department of Hematology, St. Mary’s Hospital, Kurume, Japan
Kurume, Fukuoka, Japan
TI

Toshihiro Ito

Medical Director
Department of Infectious Diseases, National Hospital Organization Sendai Medical Center, Sendai, Japan
Sendai, Miyagi, Japan
NH

Norimichi Hattori

Professor
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
Tokyo, Tokyo, Japan
SH

Satoshi Higasa

Medical Director
Department of Hematology, Hyogo College of Medicine Hospital, Nishinomiya, Japan
Nishinomiya, Hyogo, Japan
NS

Nobuaki Suzuki

Service Lecturer
Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan
Nagoya, Aichi, Japan
Yoshinobu Seki, MD, PhD

Medical Director
Department of Hematology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Japan
Minami-uonuma, Niigata, Japan
KN

Keiji Nogami

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

Background: Emicizumab is a bispecific antibody that mimics the cofactor function of activated factor (F) VIII and prevents bleeds in patients with congenital hemophilia A (PwCHA) regardless of inhibitor status. Given its mechanism of action, emicizumab would also be efficacious in patients with acquired hemophilia A (PwAHA). However, no prospective clinical studies have been performed to explore optimal dosing regimen or completion criteria for emicizumab in PwAHA.

Aims: To report the primary analysis results from a prospective, multicenter, open-label phase III study evaluating the efficacy, safety, and pharmacokinetics of emicizumab in PwAHA (AGEHA; JapicCTI-205151).

Methods: PwAHA aged ≥18 years received emicizumab subcutaneously at 6 mg/kg on Day 1 and 3 mg/kg on Day 2 followed by 1.5 mg/kg once weekly from Day 8 onwards. Dosing completion criteria comprised FVIII activity >50 IU/dL and no coagulation factor product use for bleeds within 72 hours. AGEHA was designed as a descriptive study with no primary or secondary endpoints and conducted in accordance with relevant ethical standards.

Results: By the cutoff date (April 23, 2021), 12 patients on immunosuppressive therapy had been enrolled and 11 of them (91.7%) had completed emicizumab treatment. Mean trough plasma emicizumab concentration reached steady state rapidly (1 week) achieving the efficacious level that was established in PwCHA (>30 μg/mL). During the pre-treatment period, 6 (50.0%) patients experienced 30 treated bleeds, 27 of which were major bleeds. During the on-treatment period, 5 treated bleeds occurred in 2 (16.7%) patients, and no major bleeds occurred in any patient (Figure). Emicizumab was well tolerated with no treatment discontinuation. One asymptomatic, non-serious deep vein thrombosis was reported during emicizumab treatment and resolved without any treatment. No patients developed anti-emicizumab antibodies impacting pharmacokinetics (Table).

Conclusion(s): These results suggest emicizumab prophylaxis with the tested dosing regimen and completion criteria has a favorable benefit–risk profile in PwAHA.