Slide 1: Endogenous FVIII activity and procedure-related FVIII use and bleeding: Post hoc analysis of GENEr8-1
Endogenous FVIII activity and procedure-related FVIII use and bleeding: Post hoc analysis of GENEr8-1 Doris V Quon, MD, PhD1; Jiaan-Der Wang, MD, PhD2; Michael Wang, MD3; Dominic Pepperell, MB BS4; Young Shil Park, MD, PhD5; Gili Kenet, MD6; Johnny Mahlangu, BSc, MB BCh, MMed, FCPath7; Teh-Liane Kho
Slide 2: Disclosures for Doris V Quon
Disclosures for Doris V Quon Research support/principal BioMarin Pharmaceutical Inc., Bioverativ/Sanofi, investigator Roche/Genentech, Shire/Takeda, and uniQure Employee No relevant conflicts of interest to declare Consultant Roche/Genentech, Novo Nordisk, BioMarin Pharmaceutical Inc., Bayer, Takeda
Slide 3: Evaluating endogenous FVIII activity and procedure-related FVIII use following 2 years of treatment
Evaluating endogenous FVIII activity and procedure-related FVIII use following 2 years of treatment with valoctocogene roxaparvovec • Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) transfers a FVIII coding sequence to hepatocytes using a recombinant AAV5 vector, enabling endogenous FVIII production in
Slide 4: Phase 3 GENEr8-1 study design
Phase 3 GENEr8-1 study design Eligible participants • Participants directly enrolled or were rolled over from the non-interventional study BMN 270-902 • Adult men with severe haemophilia A (FVIII ≤1 IU/dL) • Previously receiving FVIII prophylaxis • No history of FVIII inhibitors or anti-AAV5 antibod
Slide 5: Baseline demographics and characteristics of ITT population
Baseline demographics and characteristics of ITT population ITT Baseline characteristics1 n=134 Age, years, mean ± SD 31.7 ± 10.3 Race, n (%) White 96 (71.6) Asian 19 (14.2) Black or African American 15 (11.2) Hawaiian or Pacific Islander 1 (0.7) Not provided 3 (2.2) Hispanic or Latino ethnicity, n
Slide 6: Procedures performed during GENEr8-1
Procedures performed during GENEr8-1 • In total, 77 participants underwent 260 total procedures • Types of procedures1 ‒ Non-invasive: eg, tattoo, dental cleaning ‒ Invasive: o Major: eg, joint debridement, arthrodesis o Minor: eg, dental extraction, biopsies • PIs were sent questionnaires asking wh
Slide 7: Perioperative management for participants in GENEr8-1
Perioperative management for participants in GENEr8-1 • Major invasive procedures were performed with Minor invasive Major invasive FVIII treatment regardless of participant FVIII level procedures procedures • Compared with minor procedures, major Mean FVIII dose, IU/kg 67.2 255.4 (min/max) (14–324)
Slide 8: Minor invasive procedures without FVIII associated with higher FVIII activity per CSA
Minor invasive procedures performed without FVIII treatment were associated with higher participant FVIII activity per CSA 150 45 45 Minor without FVIII Minor withou Number of procedures Number of procedures 40 40 Minor with Minor FVIII with F Mean FVIII activity 35 35 Major with Major FVIII with F
Slide 9: Relatively few invasive procedure–related bleeds occurred
Relatively few invasive procedure–related bleeds occurred • There were 18 procedure-related bleeding episodes in 14 participants 300 Minor without FVIII 250 Minor with FVIII • Bleeding episodes were self-reported by 200 Major with FVIII Mean FVIII activity participants (IU/dL per CSA) Procedures wit
Slide 10: Effective haemostatic control was possible for participants of the GENEr8-1 trial
Effective haemostatic control was possible for participants of the GENEr8-1 trial FVIII, factor VIII; PI, principal investigator; WFH, World Federation of Hemophilia. 1. Srivastava A, et al. Haemophilia. 2020;26(suppl 6):1-158. 10
Slide 11: Conclusions
Conclusions • In the GENEr8-1 clinical trial of valoctocogene roxaparvovec for severe haemophilia A, 67 out of 111 invasive procedures were performed without FVIII treatment ‒ Most minor invasive procedures (62/67) were safely performed without bleeding events ‒ For minor invasive procedures, FVIII
Slide 12: Acknowledgements
Acknowledgements Thank you to all the trial participants, their families, study site personnel, and investigators • Funding for this study was provided by BioMarin Pharmaceutical Inc. • Medical writing and editorial support were provided by Tony Sallese, PhD, of AlphaBioCom, LLC, and funded by BioMa