OC 21.5 - Comparative effectiveness of valoctocogene roxaparvovec and prophylactic factor VIII replacement estimated through propensity scoring

Sunday, July 10, 2022

3:45 PM – 4:00 PM

Location: ExCel Center, S11A

Presentation Format: In-Person

Co-Author(s)

HL

Hai Liu

Director, Biostatistics
BioMarin Pharmaceutical, Inc.
Novato, California, United States
CH

Charles Hawes, MSc

Director, Health Economics and Outcomes Research and Market Access
BioMarin Europe Ltd
London, England, United Kingdom
CH

Chienting Hsu

Principal Analyst, Statistical Programming
BioMarin Pharmaceutical, Inc.
Novato, California, United States
PY

Phil You

Senior Director, Head of Global Medical Affairs Biostatistics
BioMarin Pharmaceutical, Inc.
Novato, California, United States
XY

Xinqun Yang

Executive Director, Biostatistics
BioMarin Pharmaceutical, Inc.
Novato, California, United States
VN

Vanessa Newman

Executive Director, Medical Affairs
BioMarin Europe Ltd
London, England, United Kingdom
TR

Tara M. Robinson

Medical Director, Clinical Science
BioMarin Pharmaceutical Inc., Novato, CA, USA
Novato, California, United States

Presenting Author(s)

Anthony J. Hatswell, PhD

Director
Delta Hat
Nottingham, England, United Kingdom

Co-Author(s)

DH

David Hinds

Director, Epidemiology and Real World Evidence
BioMarin Pharmaceutical, Inc.
Novato, California, United States

Background: A prospective, noninterventional study (NIS) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). Of these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913), which evaluated the efficacy and safety of valoctocogene roxaparvovec—an adeno-associated virus serotype 5 (AAV5) gene therapy that transfers a B-domain deleted FVIII cDNA to hepatocytes—in adults with SHA without preexisting anti-AAV5 antibodies or FVIII inhibitors.

Aims: To compare bleeding outcomes among adults with SHA treated with valoctocogene roxaparvovec vs prophylactic FVIII replacement using propensity scoring.

Methods: Post-hoc analysis of the 112 participants who rolled over into GENEr8-1 (intervention cohort) compared to 73 participants enrolled in the NIS who were negative for FVIII inhibitors, anti-AAV5 antibodies, and HIV; had ≥6 months follow-up; and did not enroll in GENEr8-1 (control cohort). Comparable cohorts were generated based on propensity scores (PS) using standardized mortality ratio weighting (SMRW) to weight the control cohort to match baseline characteristics of the intervention cohort. Cohorts were compared regarding mean annualized bleeding rate (ABR, treated and all bleeds) and the proportion of participants with zero bleeds (treated and all bleeds). Additional PS adjustment methodologies were evaluated.

Results: Baseline characteristics between cohorts were more similar after PS adjustment with generally smaller standardized mean differences (SMD) post-weighting (Table 1). Mean treated and all bleeds ABR were significantly lower (absolute differences of –3.6 (P < 0.001) and –3.6 (P < 0.001), respectively) in the intervention vs control cohorts (Table 2). Proportions of participants with zero treated (79.5% vs 32.9%; P< 0.001) and all bleeds (52.7% vs 28.5%; P=0.003) were significantly higher in the intervention vs control cohorts (Table 2).

Conclusion(s): Results of PS analysis were consistent with GENEr8-1 findings, with participants receiving valoctocogene roxaparvovec demonstrating lower ABRs and higher proportions of participants with zero bleeds than participants receiving prophylactic FVIII. Funded by BioMarin.