Slide 1: Seven-Year Follow-Up of Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A
SEVEN-YEAR FOLLOW-UP OF VALOCTOCOGENE ROXAPARVOVEC GENE THERAPY FOR HEMOPHILIA A Bella Madan1, Emily Symington2, Savita Rangarajan3, Will Lester4, Glenn F. Pierce5, Priyanka Raheja6, Carolyn M. Millar7, Dane Osmond8, Mingjin Li8, Tara M. Robinson8, Giancarlo Castaman9 1Guy’s and St Thomas’ NHS Found
Slide 2: Disclosures
Disclosures • I have received grant/research support from CSL Behring, Pfizer and Sobi; acted as a consultant for Ablynx, Alexion, Bayer, CSL Behring, Novo Nordisk, Pfizer, Roche, Sanofi, Sobi, Takeda and uniQure; and have participated in a speaker bureau for Bayer, Bioviix, Grifols, Kedrion, Novo N
Slide 3: 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 FVIII coding sequence to enable FVIII production in people with severe hemophilia A (FVIII ≤1 IU/dL)1,2 In the most recent publication of the phase 1/2 tri
Slide 4: Dosing schema and baseline characteristics
Dosing schema and baseline characteristics 15 participants enrolled and dosed in 4 cohorts 6x1013 vg/kg 4x1013 vg/kg Baseline characteristics cohort cohort (n = 7) (n = 6) Age, years Mean (SD) 30.4 (5.8) 31.3 (9.6) 1 participant in the 6x1012 vg/kg dose cohort Median 30.0 30.5 Min, max 23.0, 42.0 22
Slide 5: No new safety signals in years 6−7
No new safety signals in years 6−7 6x1013 vg/kg cohort 4x1013 vg/kg cohort In the last year: (n = 7) (n = 6) n (%) Y7 Y6 No ALT elevations reported Any AE 5 (71.4) 4 (66.7) Any SAE 1 (14.3)† 0 One participant in each cohort reported Any treatment-related AE 1 (14.3)¥ 1 (16.7)£ grade 1 treatment-rela
Slide 6: Reduction in treated bleeds maintained over 6−7 years
Reduction in treated bleeds maintained over 6−7 years 6x1013 vg/kg cohort (n = 7*): 4x1013 vg/kg cohort (n = 6): ABR for treated bleeds decreased 96% ABR for treated bleeds decreased 88% from baseline to year 7 from baseline to year 6 Mean ABR over entire study Mean ABR over entire study observation
Slide 7: Reduction of FVIII infusion rate maintained through 6−7 years
Reduction of FVIII infusion rate maintained through 6−7 years 6x1013 vg/kg cohort (n = 7*): 4x1013 vg/kg cohort (n = 6): AFR decreased 95% from baseline to year 7 AFR decreased 93% from baseline to year 6 Mean AFR over entire study Mean AFR over entire study observation period = 6.4 infusions/y obse
Slide 8: FVIII activity rate of decline slowed in the last year
FVIII activity rate of decline slowed in the last year 6x1013 vg/kg cohort (n = 7) 4x1013 vg/kg cohort (n = 6) Values from participants who returned to prophylaxis were excluded after they returned to prophylaxis to reflect the true treatment effect by removing the impact from resuming prophylaxis.
Slide 9: Individual participant FVIII activity over time per CSA
Individual participant FVIII activity over time per CSA 6x1013 vg/kg cohort (n = 7) 4x1013 vg/kg cohort (n = 6) *Participant 13 lost to follow-up. 9 CSA, chromogenic substrate assay; FVIII, factor VIII; IU, international unit; vg, vector genomes.
Slide 10: Participants had improvements in ABR and FVIII infusion rates
Participants had improvements in ABR and FVIII infusion rates 6x1013 vg/kg cohort (n = 7) 4x1013 vg/kg cohort (n = 6) Participants 6 and 8 resumed FVIII prophylaxis during Y7. FVIII activity is for week 364 for the 6x1013 vg/kg cohort and week 312 for the 4x1013 vg/kg cohort (week 286 for participan
Slide 11: Conclusions
Conclusions After 6−7 years, a single infusion of valoctocogene roxaparvovec provided durable bleeding protection with an acceptable safety profile No new safety signals Durable hemostatic efficacy • No ALT elevations in years 6−7 • Rate of treated bleeds during • No FVIII inhibitors or thromboembol
Slide 12: Acknowledgements
Acknowledgements • We thank all the trial participants, their families, and study-site personnel • Medical writing support was provided by Taryn Bosquez-Berger, PhD, of AlphaBioCom, a Red Nucleus company, and funded by BioMarin Pharmaceutical Inc. • Project management support was provided by Gillian