Slide 1: Hemostatic response is maintained for up to 5 years following valoctocogene roxaparvovec
Hemostatic response is maintained for up to 5 years following treatment with valoctocogene roxaparvovec, an AAV5-hFVIII-SQ gene therapy for severe hemophilia A K John Pasi1; Savita Rangarajan2; Tara M Robinson3; Will Lester4; Emily Symington5; Bella Madan6; Michael Laffan7; Mingjin Li3; Benjamin Kim
Slide 2: Disclosures for Michael Laffan
Disclosures for Michael Laffan In compliance with COI policy, ISTH requires the following disclosures to the session audience: Research Support/PI BioMarin Pharmaceutical Employee No relevant conflicts of interest to declare Consultant Bayer, LEO Pharma, LFP Biopharmaceuticals, Pfizer, Roche, Shire,
Slide 3: Valoctocogene roxaparvovec gene therapy for severe hemophilia A
Valoctocogene roxaparvovec gene therapy for severe hemophilia A • Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) transfers a FVIII coding sequence to hepatocytes using a recombinant AAV5 vector, enabling endogenous FVIII production in people with hemophilia A1,2 • Here, we present updated safety and ef
Slide 4: Participant disposition and baseline characteristics
Participant disposition and baseline characteristics 15 participants enrolled and dosed in 4 cohorts 6x1013 vg/kg 4x1013 vg/kg cohort cohort Baseline characteristics (n = 7) (n = 6) Age, years 1 participant in the 6×1012 vg/kg dose cohort Mean (SD) 30.4 (5.8) 31.3 (9.6) Median 30.0 30.5 Min, max 23.
Slide 5: Safety
Safety 6x1013 vg/kg cohort (n = 7) 4x1013 vg/kg cohort (n = 6) n Y1 Y2 Y3 Y4 Y5 Y1 Y2 Y3 Y4 Any AE 7 6 7 7 6 6 5 5 4 Any SAE 0 1 1 1 0 1 0 1 1 Any treatment-related AE 6 1 1 2 0 6 0 0 0 Any treatment-related SAE 0 0 0 0 0 1 0 0 0 AEs of special interest ALT elevation 6 0 0 1 1 4 0 1 0 AEs of liver d
Slide 6: Sustained reduction in annualized treated bleeding rate
Sustained reduction in annualized treated bleeding rate 6x1013 vg/kg dose cohort (n = 6*) 4x1013 vg/kg dose cohort (n = 6) 20 20 Median Mean ABR after week 4 Mean ABR after week 4 16.5 16.3 Median Mean = 0.8 bleeds/yr = 1.0 bleeds/yr Mean 15 15 ABR (no./year) ABR (no./year) 95% reduction from 92% re
Slide 7: Sustained reduction in annualized FVIII infusion rate
Sustained reduction in annualized FVIII infusion rate 6x1013 vg/kg dose cohort (n = 6*) 4x1013 vg/kg dose cohort (n = 6) 200 Mean AFR after week 4 200 Mean AFR after week 4 Median = 5.2 infusions/yr Median = 7.8 infusions/yr Mean 155.8 Mean 96% reduction from 142.8 95% reduction from 150 136.5135.6
Slide 8: FVIII activity over time
FVIII activity over time 180 180 180 Legend 6x10 13 vg/kg cohort Legend 6x10 13 vg/kg cohort Legend 4x10 13 vg/kg cohort 160 4E13 Week 208 FVIII Activity Legend 6E13 Week4x10 260 FVIII 13 Activity vg/kg cohort 160 160 Mean Mean 5.6 by CSA (9.5 by OSA) Mean 11.6 by CSA (18.7 by OSA) Mean Median Media
Slide 9: FVIII activity rate of change over time
FVIII activity rate of change over time 0 50 100 150 200 250 Regression of FVIII by follow-up year Regression of FVIII by follow-up year IU/dL/wk Year 1 Year 2 Year 3 Year 4 Year 5 IU/dL/wk Year 1 Year 2 Year 3 Year 4 Slope 1.01 −0.24 −0.15 −0.27 −0.14 Slope 0.35 −0.15 −0.08 −0.06 95% CI −0.04, 2.05
Slide 10: Comparison to Phase 3 GENEr8-1 Study
Comparison to Phase 3 GENEr8-1 Study GENEr8-1 Weeks 49–52 GENEr8-1 Week 104 GENEr8-1 Weeks 49–52 GENEr8-1 Week 104 Mean 42.2, n = 17 Mean 24.4, n = 17 Mean 42.2, n = 17 Mean 24.4, n = 17 0 50 100 150 200 250 FVIII levels from the phase 3 GENEr8-1 study were below those of the 6x1013 vg/kg cohort and
Slide 11: Individual participant FVIII activity per chromogenic assay: 6x10^13 vg/kg cohort
Individual participant FVIII activity per chromogenic assay 6x1013 vg/kg cohort 140 120 100 FVIII activity (IU/dL) 80 60 40 20 0 0 26 52 104 156 208 260 Study week Participant 5 Participant 7 Participant 8 Participant 6 11 Participant 4 Participant 3 Participant 9 FVIII, factor VIII.
Slide 12: Individual participant FVIII activity per chromogenic assay: 4x10^13 vg/kg cohort
Individual participant FVIII activity per chromogenic assay 4x1013 vg/kg cohort 40 30 FVIII activity (IU/dL) 20 10 0 0 26 52 104 156 208 Study week Participant 11 Participant 14 Participant 12 12 Participant 10 Participant 13 Participant 15 FVIII, factor VIII.
Slide 13: Individual participant FVIII infusion rate, ABR, and FVIII activity
13 4x10 Individual participant vg/kg cohort FVIII infusion (n =and rate, ABR, 6) FVIII activity CS OS Baseline After week 4 Baseline After week 4 6x1013 vg/kg dose cohort (n = 7) 4x1013 vg/kg dose cohort (n = 6) 13 6x10 FVIII vg/kg Current Participant cohort 11 Annualized treated (n = 7) 41 FVIII An
Slide 14: Haemo-QoL-A Total Score over time
Haemo-QoL-A Total Score over time Haemo-QoL-A Total Score 100 (mean ± SD) 80 60 Baseline 6x1013 vg/kg cohort 50 4x1013 vg/kg cohort 0 Year 0 1 2 3 4 5 6x1013 vg/kg n = 7 7 5 6 6 7 4x1013 vg/kg n = 6 4 6 6 5 14 Haemo-QoL-A, hemophilia-specific quality of life questionnaire for adults; SD, standard de
Slide 15: Conclusions
Conclusions Ø Safety profile remains unchanged from previous reports Ø No systemic hypersensitivity, anaphylaxis, or thromboembolic events Ø No participants developed FVIII inhibitors Ø Increased clarity on the trajectory of FVIII activity levels over time Ø ABR and FVIII utilization reductions from
Slide 16: Acknowledgements
Acknowledgements • Thank you to all the trial participants, their families, study-site personnel, and investigators • We thank Stefan Tiefenbacher and Mary Robinson of Esoterix for FVIII assays and consulting and the following employees of BioMarin Pharmaceutical: Kala Jayaram for safety assessments