OC 40.5 - Crimson 1: A Phase 3 study to evaluate the efficacy and safety of subcutaneous marzeptocog alfa (activated) for on-demand treatment of bleed events in subjects with hemophilia A or B, with inhibitors

Monday, July 11, 2022

3:45 PM – 4:00 PM

Location: ExCel Center, ICC Auditorium

Presentation Format: In-Person

Presenting Author(s)

Savita Rangarajan, MD, FRCP, FRCPath

Associate Professor of Clinical Haematology
Faculty of Medicine, University of Southampton, Southampton, UK
Southampton, England, United Kingdom

Co-Author(s)

SD

Shraddha Desai

Senior Director, Clinical Science
Catalyst Biosciences
South San Francisco, California, United States
SA

Shashikant Apte

Director
Sahyadri Speciality Hospital, Pune, Maharashtra, India
Pune, Maharashtra, India
DV

Dharmesh Vaghasiya

Department Head, Hematology and BMT
Sahyadri Super Specialty Hospital
Pune, Maharashtra, India
Johnny Mahlangu, MD, MMed

Professor in Haematology
University of the Witwatersrand and NHLS
Johannesburg, South Africa
VR

Vijay M. Ramanan

Honorary Consultant, Haemotologist/Haem-Oncologist, and BMT Physician
Grant Medical Foundation, Ruby Hall Clinic
Pune, Maharashtra, India
LM

Levani Makhaldiani

Head of Centre and Hemophilia and Thrombosis
K.Eristavi National Centre of Experimental and Clinical Surgery
Tbilisi, Guatemala, Georgia
BK

Bartosz Korczowski

Head of Pediatrics, Gastroenterology,
Institute of Medical Sciences, Medical College, University of Rzeszów
Rzeszów, Podkarpackie, Poland
MT

Margarita Timofeeva

Surgeon
Federal State Budgetary Scientific Institution,Kirov Research Institute of Hematology and Blood Transfusion of Federal Medical and Biological Agency
Kirov, Kirov, Russia
SV

Svetlana Volkova

Hematologist
MEDIS, LLC
Novgorod, Novgorod, Russia
SP

Susmitha Pinnamaraju

Senior Manager, Data Management Consultant
Catalyst Biosciences
South San Francisco, California, United States
JY

Jang Yun

Director, Biostatistics
Catalyst Biosciences
South San Francisco, California, United States
LN

Linda Neuman

VP, Clinical Development Consultant
Catalyst Biosciences
South San Francisco, California, United States
TK

Tom Knudsen

Senior VP, Corporate Development
Catalyst Biosciences
South San Francisco, California, United States
BK

Benjamin Kim

VP, Clinical Development and Clinical Operations
Catalyst Biosciences
South San Francisco, California, United States

Background: A significant number of persons with hemophilia A (PwHA) or PwHB develop inhibitors to FVIII or FIX, respectively, and become refractory to factor replacement treatment. Marzeptocog alfa (activated; MarzAA) is an engineered, activated FVII (FVIIa) with improved pharmacokinetics developed for subcutaneous (SC) administration in PwHA/PwHB with inhibitors.

Aims: To evaluate the efficacy and safety of MarzAA versus standard of care (SOC; i.e., NovoSeven®, recombinant FVIIa [rFVIIa], or activated prothrombin complex concentrate) for treatment of bleeds in PwHA/PwHB with inhibitors.

Methods: Enrollment of approximately 60 subjects was planned (consented per local Ethics Committee) to observe a total of 488 eligible, treated bleeds, 244 with each treatment type in a cross-over study design, to demonstrate non-inferiority (margin: -0.12) in effective treatment (investigator assessment of “Excellent” or “Good” hemostasis at 24 hours after initial dose) with MarzAA versus SOC.

Results: Due to changes in business strategy, the Sponsor terminated enrollment and dosing early on 15 November 2021. At that time, 18 subjects had been randomized and enrolled, with observation of 74 eligible bleeds (30 and 44 bleeds in 8 and 11 subjects treated with MarzAA and SOC, respectively). The proportion of effective treatment at 24 hours post-initial dose was 86.2% versus 86.5% for subjects treated with MarzAA versus SOC, respectively. One subject treated with SOC reported a serious adverse event of ureterolithiasis unrelated to treatment. No thromboembolic events were reported. One subject treated with MarzAA was found to have low-titer cross-reactive anti-drug antibodies (ADAs) with neutralizing antibody assessments pending.

Conclusion(s): While this study was terminated early by the Sponsor, the accumulated data suggest that SC MarzAA has the potential to treat bleeding episodes safely and effectively in PwHA/PwHB with inhibitors. Further investigation into ADAs in one subject will be reported at the Congress.