Pfizer announced positive topline results from the Phase 3 AFFINE study evaluating giroctocogene fitelparvovec, an investigational gene therapy for the treatment of adults with moderately severe to severe hemophilia A. The study met its primary objective, demonstrating non-inferiority and superiority in total annualized bleeding rate (ABR) compared to routine Factor VIII (FVIII) replacement prophylaxis.
Efficacy and Safety Results
The AFFINE study showed that a single 3e13 vg/kg dose of giroctocogene fitelparvovec resulted in a statistically significant reduction in mean total ABR compared to the pre-infusion period (1.24 vs 4.73; one-sided p-value=0.0040). Key secondary endpoints were also met, demonstrating superiority compared to prophylaxis. Specifically, 84% of participants maintained FVIII activity >5% at 15 months post-infusion (one-sided p-value = 0.0086), with the majority having FVIII activity ≥15%. The mean treated ABR showed a statistically significant 98.3% reduction from 4.08 in the pre-infusion period to 0.07 post-infusion (from Week 12 up to at least 15 months; one-sided p-value < 0.0001).
The gene therapy was generally well-tolerated. Transient elevated FVIII levels ≥150% were observed in 49.3% of dosed participants, as measured via chromogenic assay, without impacting efficacy and safety results. Serious adverse events were reported in 15 patients (20%), with 13 events reported by 10 patients (13.3%) assessed as treatment-related. These treatment-related adverse events generally resolved with clinical management.
Clinical Significance
Professor Andrew Leavitt M.D., lead investigator of the AFFINE trial, emphasized the transformative potential of giroctocogene fitelparvovec. "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."
About Giroctocogene Fitelparvovec
Giroctocogene fitelparvovec is an investigational gene therapy that includes a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation FVIII gene. The goal is to enable patients to produce FVIII themselves for an extended period, reducing the need for routine prophylaxis with intravenous infusions or injections.
Hemophilia A Context
Hemophilia A is an inherited bleeding disorder affecting approximately 25 in every 100,000 male births worldwide. It results from a deficiency in clotting factor VIII, leading to prolonged bleeding. Approximately 55-75% of males with hemophilia A have a moderate to severe form of the disease, requiring constant monitoring and therapy.
Trial Design and Further Steps
The Phase 3 AFFINE study (NCT04370054) was an open-label, multicenter, single-arm study involving 75 adult male participants with moderately severe to severe hemophilia A. Participants were screened to ensure they tested negative for neutralizing antibodies to the gene therapy vector. They will be evaluated over five years in the AFFINE study and up to 15 years in a long-term follow-up study. Pfizer plans to discuss these data with regulatory authorities in the coming months. The FDA has granted giroctocogene fitelparvovec Fast Track and Regenerative Medicine Advanced Therapy designations, as well as Orphan Drug designations in the U.S. and the European Union.
