Giroctocogene Fitelparvovec Reduces Total Annualized Bleeding Rate for Hemophilia A
The investigational drug achieved non-inferiority compared to routine Factor VIII.
Giroctocogene fitelparvovec achieved non-inferiority and superiority for the total annualized bleeding rate (ABR) compared to routine Factor VIII (FVIII) replacement prophylaxis treatment from week 12 through at least 15 months, according to data from the AFFINE study (NCT04370054). Further, after a single 3e13 vg/kg dose, the study drug showed statistically significant reductions in mean total ABR when compared to the pre-infusion period.1
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“For people living with hemophilia A, the physical and emotional impact of needing to prevent and treat bleeding episodes through frequent IV infusions or injections cannot be underestimated,” said Andrew Leavitt, MD, study lead investigator and professor at the department of laboratory medicine and director of medicine in the division of hematology/oncology at the Adult Hemophilia Treatment Center at the University of California San Francisco, in a new release. “I’m excited by the strength of these positive results from the AFFINE trial that show giroctocogene fitelparvovec was generally well tolerated, and demonstrate the transformative potential of this gene therapy candidate to provide superior bleed protection compared with routine FVIII prophylaxis, while helping relieve the treatment burden for people living with hemophilia A.”1
In 2020, follow-up data from the phase 1 and phase 2 Alta study (NCT03061201) were presented at the 62nd American Society of Hematology Annual Meeting, showing that all 5 patients in the high dose 3 x 1013 vg/kg cohort sustained FVIII levels. There was a median FVIII activity of 56.9% and a group geometric mean FVIII activity of 70.4% from week 9 to week 52, as previously discussed in an article on Pharmacy Times.2
Investigators of the study included males who had been followed on routine FVIII prophylaxis therapy during the lead-in study and had greater than 150 documented exposure days to FVIII protein, according to the clinical trial information. Further, individuals had moderately severe to severe hemophilia A and suspension of FVIII prophylaxis therapy post-study drug infusion. Patients received an infusion of giroctocogene fitelparvovec as a single IV infusion. The primary outcome was total annualized ABR at 15 months, and secondary outcomes were FVIII activity levels at 15 months, ABR at 15 months, annualized infusion rate of exogenous FVIII activity at 15 months, annualized FVIII consumption at 15 months, ABR and total ABR of specific type by cause and by location at 15 months, change in joint health using Hemophilia Joint Health Score, patient-reported outcome instrument Hemophilia Activities List, patient-reported outcome instrument Haemophilia Quality of Life Questionnaire for Adults, and incidence and severity of adverse events (AEs).3
The investigators reported that the secondary end point was met and demonstrated superiority compared to prophylaxis, with 84% of individuals maintaining FVIII activity of more than 5% at 15 months post-infusion. Additionally, the majority of individuals had FVIII activity of 15% or more. Investigators also reported that the mean treated ABR was statistically significant, with a 98.3% reduction from 4.08 for the pre-infusion period compared to 0.07 post-infusion. Only 1 patient returned to prophylaxis post-infusion.1
Giroctocogene fitelparvovec was generally well tolerated, with transient elevated FVIII levels of 150% or greater shown in 49.3% of those who received the drug, with no impact on either efficacy or safety. Approximately 20% reported serious AEs, with 13.3% being related to treatment.1
