Eptacog beta efficacy and safety in underweight, normal weight, and overweight/obese persons with hemophilia A or B and inhibitors

Authors: Rafique, A.; Srivastava, A.; Abajas, Y.; Acharya, S.; Ahuja, S.; Román, M.T.Á.; Carcao, M.; Dargaud, Y.; Dunn, A.; Hermans, C.; McGuinn, C.; Miesbach, W.; Reding, M. T.; Windyga, J.; Bonzo, D.; Mitchell, I. S.; Wilkinson, T. A.; Meeks, S.

Publication: Research and Practice in Thrombosis and Haemostasis. 2023. 7

ABSTRACT: BACKGROUND: Being overweight or obese increases the disease burden faced by persons with hemophilia, and the prevalence of these comorbidities in persons with hemophilia may be rising along with that of the general population [1]. Eptacog beta is a recombinant activated human factor VII proven to be safe and effective for the treatment and control of bleeding episodes (BEs) in persons with hemophilia A or B with inhibitors (PwHABI) ≥12 years of age. The pivotal phase 3 trial (PERSEPT 1; NCT02020369) included 27 subjects ages ≥12 years who treated 465 mild or moderate BEs using eptacog beta initial dose regimens (IDRs) of 75 and 225 μg/kg. OBJECTIVES: To evaluate eptacog beta efficacy and safety when treating mild or moderate BEs with 75 and 225 μg/kg IDRs in underweight (body mass index [BMI] <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), and overweight (BMI 25.0-29.9 kg/m2) or obese (BMI ≥30.0 kg/m2) PwHABI from PERSEPT 1, at 12 and 24 hours post-initial dose of eptacog beta. METHODS: PERSEPT 1 was a prospective, global, open-label trial using 75 and 225 μg/kg IDRs in a randomized crossover design. Subjects initially treated mild or moderate BEs with 75 or 225 μg/kg eptacog beta, followed either 3 hours (75 μg/kg IDR) or 9 hours later (225 μg/ kg IDR) with 75 μg/kg q3h as needed. Treatment success was defined as obtaining a hemostasis evaluation of “excellent” or “good” with no use of additional eptacog beta, alternative hemostatic agents or blood products, and no increase in pain following the first “excellent” or “good” assessment. RESULTS: Eight PERSEPT 1 subjects were underweight and treated 193 BEs; 12 were of normal weight and treated 198 BEs; and 7 were overweight or obese and treated 74 BEs. At 12 hours, the 225 μg/kg IDR showed increased treatment success proportions over the 75 μg/ kg IDR (p<0.01) for both normal weight and overweight/obese groups (Fig. 1). At 24 hours post-initial eptacog beta infusion, nearly all BEs in each BMI group were successfully treated (89-98% for the 75 μg/kg IDR and 98-100% for the 225 μg/kg IDR; Table 1 and Fig. 1). Six treatment-related adverse events (TRAEs; 4 infusion site discomfort [Table presented] and 2 infusion site hematoma events) were experienced in the normal weight group and 1 TRAE (increased body temperature) was experienced in the underweight group; all TRAEs resolved and were considered mild in nature. No thromboembolic, allergic, hypersensitivity, or anaphylactic events occurred, and no neutralizing antieptacog beta antibodies were detected in any BMI group. CONCLUSIONS: Increased efficacy was achieved at 12 hours with the 225 μg/kg IDR over the 75 μg/kg IDR in the normal weight and overweight/obese groups. Eptacog beta was well tolerated in subjects across all BMI groups; no thromboembolic events were experienced by any subjects, including those in the overweight/obese group. With the high efficacy seen at 24 hours, eptacog beta offers an important treatment option for PwHABI of all BMI classes.