Plasma-derived factor VIIa and factor X mixture agent (MC710) prophylaxis in haemophilia B patients with inhibitors

Authors: Sakai, M; Amano, K; Chin, M; Takedani, H; Ishida, H; Sakashita, K; Taki, M; Migita, M; Watanabe, H; Ishimura, M; Nogami, K; Harano, S; Shirahata, A

Affiliations: Department of Pediatrics, Munakata Suikokai General Hospital, Fukuoka, Japan. Department of Laboratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan. Department of Pediatrics, Nihon University Itabashi Hospital, Tokyo, Japan. Department of Joint Surgery, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Publication: Haemophilia 2022

Abstract: INTRODUCTION: Haemophilia B patients with factor IX inhibitors have particularly unmet needs for conventional therapy. AIM: Phase II/III clinical trial, multicentre, open-label, prospective, self-controlled study was conducted to assess MC710 prophylaxis in haemophilia B patients with inhibitors. METHODS: We enrolled haemophilia patients who had received episodic or prophylactic treatment with bypassing agents up to that time. The participants continued their conventional therapy for 24 weeks and then MC710 was prophylactically infused intravenously every 2 or 3 days at 60 to 120 μg as FVIIa per kilogram of body weight for 24 weeks. The primary endpoint was the annual bleeding rate (ABR) requiring bypassing agents, which was compared intraindividually between the conventional therapy period and the MC710 prophylaxis period. RESULTS: A total of 11 male haemophilia B patients were enrolled. The median ABR ratio for each participant (the prophylaxis period ABR divided by the conventional therapy period ABR) was .33 (2.1/6.5), range from .00 to 3.77. ABR ratios for 9 of the 11 patients ranged from .00 to .60, and 3 of the 9 patients had zero bleeding events during the prophylaxis period. Meanwhile, ABR ratios for the remaining two patients were 2.53 and 3.77, respectively. Although a fibrinogen decrease recovered by the dose reduction was reported for only one participant as the sole adverse drug reaction in this study, no thrombotic events or other safety concerns were reported. CONCLUSION: MC710 prophylaxis is considered to be decrease the bleeding rate in haemophilia B patients with inhibitors without safety concerns.