Slide 1: Efficacy and Safety of Valoctocogene Roxaparvovec 4 Years After Gene Transfer in GENEr8-1
EFFICACY AND SAFETY OF VALOCTOCOGENE ROXAPARVOVEC 4 YEARS AFTER GENE TRANSFER IN GENER8-1 Andrew D. Leavitt1, Johnny Mahlangu2, Priyanka Raheja3, Emily Symington4, Doris V. Quon5, Adam Giermasz6, Gili Kenet7, Gillian Lowe8, Nigel S. Key9, Carolyn M. Millar10,11, Steven W. Pipe12, Bella Madan13, Shen
Slide 2: Efficacy and safety of valoctocogene roxaparvovec 4 years after gene transfer in GENEr8-1
Efficacy and safety of valoctocogene roxaparvovec 4 years after gene transfer in GENEr8-1 1Adult Hemophilia Treatment Center, University of California San Francisco, San Francisco, CA, USA; 2Hemophilia Comprehensive Care Center, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witw
Slide 3: Disclosures
Disclosures • I have acted as a speaker or member of a speaker bureau for Grifols and Roche, and have served on advisory boards for BioMarin, Roche, Sanofi, Sobi and Takeda 3
Slide 4: Valoctocogene roxaparvovec for severe hemophilia A
Valoctocogene roxaparvovec for severe hemophilia A Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is a liver-directed gene therapy that transfers a B-domain-deleted FVIII coding sequence to enable FVIII production in people with severe hemophilia A (FVIII ≤1 IU/dL)1,2 In the open-label, phase 3 GENEr8-
Slide 5: Study design
Study design Eligibility Endpoints • Adult men with severe hemophilia A (FVIII ≤1 IU/dL) • FVIII activity • Previously receiving FVIII prophylaxis • Change from baseline • No history of FVIII inhibitors or anti-AAV5 antibodies — Annualized bleeding rate • No significant liver dysfunction, fibrosis,
Slide 6: Participant disposition
Participant disposition Rollover from BMN 270-902, N = 112 Directly enrolled, n = 22 ITT population All participants infused, N = 134 mITT population HIV-negative, N = 132 HIV-positive and enrolled ≥5 years, n = 2 Enrolled ≥5 years, n = 17 Discontinued from study, n = 5 • Lost to follow-up, n = 2 •
Slide 7: Baseline characteristics
Baseline characteristics Rollover population mITT ITT Baseline characteristics N = 112 N = 132 N = 134 Age, years, mean (range) 31.8 (19–70) 31.4 (18–70) 31.7 (18–70) Race, n (%) White 78 (69.6) 94 (71.2) 96 (71.6) Asian 17 (15.2) 19 (14.4) 19 (14.2) Black or African American 14 (12.5) 15 (11.4) 15
Slide 8: No new safety signals in year 4
No new safety signals in year 4 ITT population In year 4 Year 1 Year 2 Year 3 Year 4 All Participants, n (%) (N = 134) (N = 134) (N = 131) (N = 131) follow-up No new safety signals AEs 134 (100.0) 113 (84.3) 105 (80.2) 106 (80.9) 134 (100.0) • Low-grade, transient SAEs 21 (15.7) 6 (4.5) 9 (6.9) 13 (
Slide 9: ALT elevation and glucocorticoid use
ALT elevation and glucocorticoid use ITT population In year 4 With AEs in year 4 During year 4 (N = 131) 56 (42.7%) participants experienced an ALT elevation, most of which were low- ALT elevation >ULN, n (%) 21 (16.0) grade and transient ALT elevation >1.5x baseline, n (%) 55 (42.0) Used glucocorti
Slide 10: FVIII activity (chromogenic) maintained between years 3 and 4
FVIII activity (chromogenic) maintained between years 3 and 4 mITT population 100 Week 156 (N = 132) Week 208 Week 260 (n = 17) mITT mITT (N = 132) Enrolled ≥5 years Mean ± SE FVIII activity (CSA; IU/dL) Mean ± SE: 18.4 ± 2.7 IU/dL Mean ± SE: 16.1 ± 2.5 IU/dL Mean ± SE: 18.0 ± 4.9 IU/dL Median (Q1,
Slide 11: FVIII activity (chromogenic) ranges at the end of each year
FVIII activity (chromogenic) ranges at the end of year 4 mITT population Most participants remain in the mild hemophilia range 100 Median FVIII activity per CSA 10.6% 7.7% 15.9% ≥40 IU/dL 37.1% ≥5 to <40 IU/dL 80 ≥3 to <5 IU/dL <3 IU/dL (LLOQ) Participants, % 52.3% 60 55.3% 58.3% 40 50.8% 13.8% 9.8%
Slide 12: FVIII activity (one-stage) maintained between years 3 and 4
FVIII activity (one-stage) maintained between years 3 and 4 mITT population 100 Week 156 (N = 132) Week 208 Week 260 (n = 17) mITT mITT (N = 132) Enrolled ≥5 years, mITT Mean ± SE FVIII activity (OSA; IU/dL) Mean ± SE: 28.1 ± 3.6 IU/dL Mean ± SE: 27.1 ± 4.0 IU/dL Mean ± SE: 25.5 ± 7.5 IU/dL Median (
Slide 13: FVIII activity (one-stage) ranges at the end of each year
FVIII activity (one-stage) ranges at the end of year 4 mITT population Most participants remain in the mild hemophilia range 100 Median FVIII activity per OSA 18.9% 16.9% ≥40 IU/dL 27.3% ≥5 to <40 IU/dL 80 50.8% ≥1 to <5 IU/dL <1 IU/dL (LLOQ) Participants, % 60 60.6% 61.5% 56.8% 40 41.7% 20 11.4% 10
Slide 14: Reduction in treated bleeds maintained over 4 years
Reduction in treated bleeds maintained over 4 years Rollover population ABR for treated bleeds decreased >80% from In year 4, >70% of participants baseline during the post-prophylaxis period had no treated bleeds 82.6% reduction Change in mean, −4.0 (95% CI, −5.2 to −2.8); P <0.0001 Participants wit
Slide 15: Reduction of FVIII infusion rate maintained through year 4
Reduction of FVIII infusion rate maintained through year 4 Rollover population Annualized FVIII infusion rate decreased >95% from baseline during the post-prophylaxis period 95.5% reduction Change in mean, −129.8 (95% CI, −139.4 to −120.1); P <0.0001 200 135.9 128.6 AFR (infusions/year) 150 100 10.6
Slide 16: Most participants remain off prophylaxis
Most participants remain off prophylaxis ITT population Since the previous data cutoff, 7 additional Overall, 24 participants resumed prophylaxis participants resumed prophylaxis 1.0 Week of RTP Observed FVIII (CSA) Prophylactic treatment-free probability closest to RTP 0.9 0 143 143 1.1 <1.5 0.8 0
Slide 17: Conclusions
Conclusions A single infusion of valoctocogene roxaparvovec provides durable bleeding protection for 4 years with an acceptable safety profile No new safety signals Durable hemostatic efficacy • ALT elevation remained the most common AE in • Rate of treated bleeds in the post-prophylaxis year 4; non
Slide 18: Acknowledgments
Acknowledgments • Thank you to all trial participants, their families, study-site personnel, and investigators • Funding for this study was provided by BioMarin Pharmaceutical Inc. • Medical writing support was provided by Amin Ghane, PhD, of AlphaBioCom, a Red Nucleus company, and funded by BioMari