Presentation Details
| Efficacy and Safety of Eptacog Beta for Bleed Treatment in Adults and Adolescents with Hemophilia B and Inhibitors During PERSEPT 1 Meera Chitlur1, Yasmina Abajas2, Suchitra Acharya3, Sanjay Ahuja4, Jonathan Bernstein5, Elizabeth Bowhay-Carnes6, Brandon Hardesty7, Jonathan C.Roberts8, 9, Vanessa Salinas10, Craig Seaman11, Robert Sidonio Jr.12, Daniel Bonzo13, Jim Phipps14, Thomas Wilkinson15, Guy Young16. 1Central Michigan University College of Medicine/Children’s Hospital of Michigan, Carmen and Ann Adams Department of Pediatrics, Division of Hematology/Oncology, Detroit, NY, USA.2Hemophilia and Thrombosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.3Cohen Children’s Medical Center, Northwell Health, New Hyde Park, NY, USA.4Rainbow Babies & Children’s Hospital, Cleveland, OH, USA.5Hemophilia Center of Central Pennsylvania, Hershey Medical Center, Hershey, PA, USA.6UT Health San Antonio, San Antonio, TX, USA.7Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA.8Bleeding & Clotting Disorders Institute, Peoria, IL, USA.9Departments of Pediatrics and Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.10Center for Inherited Blood Disorders, Orange, CA, USA.11Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA.12Aflac Cancer and Blood Disorders Center and Emory University, Atlanta, GA, USA.13LFB-USA, Inc., Framingham, MA, USA.14HEMA Biologics, LLC, Louisville, KY, USA.15GLOVAL LLC, Broomfield, CO, USA.16Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA |
Abstract
Background:
Hemophilia B (HB) prevalence has been estimated to be 3.8 cases per 100,000 males, with inhibitors developing in 5-10% of patients receiving factor IX replacement therapy. Given the small proportion of persons with HB and inhibitors (PwHBI), data describing bleeding episode (BE) treatment and outcomes in PwHBI are scarce. Eptacog beta (Sevenfact®) is a recombinant activated human factor VII that is FDA-approved for the treatment and control of BEs in patients with hemophilia A or B with inhibitors (age ≥12 years) using an initial dose regimen (IDR) of 75 or 225µg/kg. The pivotal PERSEPT 1 trial (NCT20202369) included 2 PwHBI subjects and 25 hemophilia A subjects with inhibitors.
Objective:
To evaluate the efficacy and safety of 75 and 225µg/kg eptacog beta IDRs for mild or moderate BE treatment in PwHBI from PERSEPT 1 at 12 and 24 h post-initial dose.
Methods:
Subjects treated BEs with either the 75 or the 225µg/kg IDR in a randomized crossover trial design. Subjects using the 75µg/kg IDR received an initial 75µg/kg eptacog beta dose followed by 75µg/kg q3h as needed until BE treatment success, while subjects in the 225µg/kg IDR received 225µg/kg eptacog beta followed 9 h later by 75µg/kg q3h as needed. Mild or moderate BE treatment success was determined by patients or caregivers, and defined as obtaining a hemostasis evaluation of “good” or “excellent” with no use of additional eptacog beta, alternative hemostatic agents or blood products, and no increase in pain following the first “good” or “excellent” assessment.
Results:
Two PwHBI treated 24 BEs (all of mild or moderate severity) in PERSEPT 1. One PwHBI (Subject 1; age 12) experienced 16 joint BEs (including 5 target joint BEs). The other PwHBI (Subject 2; age 34) treated 8 BEs, 6 of which were joint BEs (including 3 target joint BEs). At 12 h post-initial infusion, treatment success proportions for BEs treated using 75 and 225µg/kg IDRs in PwHBI were 90.0% and 81.8%, respectively (Figure 1). At 24 h, the treatment success proportions were 90.9% for the 75µg/kg IDR and 100% for the 225µg/kg IDR. Treatment success proportions seen for PwHBI treating BEs with either IDR were consistent with those seen in the PERSEPT 1 trial overall (Figure 1). While assigned to the 225µg/kg IDR, Subject 1 experienced a treatment-related adverse event (increased body temperature) of moderate severity, which resolved following administration of ibuprofen and other non-steroidal anti-inflammatory medications. No neutralizing anti-drug antibodies were found in PwHBI (or in any PERSEPT 1 subject), and no thrombotic, allergic, hypersensitivity, or anaphylactic events occurred.
Conclusions:
Both eptacog beta IDRs provided safe and effective control of mild or moderate BEs in PwHBI during PERSEPT 1. Most BEs experienced by PwHBI were successfully treated at 12 h post-initial eptacog beta infusion, and all BEs in PwHBI treated with the 225µg/kg IDR had resolved at 24 h. These results support the efficacy and safety of eptacog beta for BE treatment in adult and adolescent PwHBI.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
Hemophilia B (HB) prevalence has been estimated to be 3.8 cases per 100,000 males, with inhibitors developing in 5-10% of patients receiving factor IX replacement therapy. Given the small proportion of persons with HB and inhibitors (PwHBI), data describing bleeding episode (BE) treatment and outcomes in PwHBI are scarce. Eptacog beta (Sevenfact®) is a recombinant activated human factor VII that is FDA-approved for the treatment and control of BEs in patients with hemophilia A or B with inhibitors (age ≥12 years) using an initial dose regimen (IDR) of 75 or 225µg/kg. The pivotal PERSEPT 1 trial (NCT20202369) included 2 PwHBI subjects and 25 hemophilia A subjects with inhibitors.
Objective:
To evaluate the efficacy and safety of 75 and 225µg/kg eptacog beta IDRs for mild or moderate BE treatment in PwHBI from PERSEPT 1 at 12 and 24 h post-initial dose.
Methods:
Subjects treated BEs with either the 75 or the 225µg/kg IDR in a randomized crossover trial design. Subjects using the 75µg/kg IDR received an initial 75µg/kg eptacog beta dose followed by 75µg/kg q3h as needed until BE treatment success, while subjects in the 225µg/kg IDR received 225µg/kg eptacog beta followed 9 h later by 75µg/kg q3h as needed. Mild or moderate BE treatment success was determined by patients or caregivers, and defined as obtaining a hemostasis evaluation of “good” or “excellent” with no use of additional eptacog beta, alternative hemostatic agents or blood products, and no increase in pain following the first “good” or “excellent” assessment.
Results:
Two PwHBI treated 24 BEs (all of mild or moderate severity) in PERSEPT 1. One PwHBI (Subject 1; age 12) experienced 16 joint BEs (including 5 target joint BEs). The other PwHBI (Subject 2; age 34) treated 8 BEs, 6 of which were joint BEs (including 3 target joint BEs). At 12 h post-initial infusion, treatment success proportions for BEs treated using 75 and 225µg/kg IDRs in PwHBI were 90.0% and 81.8%, respectively (Figure 1). At 24 h, the treatment success proportions were 90.9% for the 75µg/kg IDR and 100% for the 225µg/kg IDR. Treatment success proportions seen for PwHBI treating BEs with either IDR were consistent with those seen in the PERSEPT 1 trial overall (Figure 1). While assigned to the 225µg/kg IDR, Subject 1 experienced a treatment-related adverse event (increased body temperature) of moderate severity, which resolved following administration of ibuprofen and other non-steroidal anti-inflammatory medications. No neutralizing anti-drug antibodies were found in PwHBI (or in any PERSEPT 1 subject), and no thrombotic, allergic, hypersensitivity, or anaphylactic events occurred.
Conclusions:
Both eptacog beta IDRs provided safe and effective control of mild or moderate BEs in PwHBI during PERSEPT 1. Most BEs experienced by PwHBI were successfully treated at 12 h post-initial eptacog beta infusion, and all BEs in PwHBI treated with the 225µg/kg IDR had resolved at 24 h. These results support the efficacy and safety of eptacog beta for BE treatment in adult and adolescent PwHBI.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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