AFFINE Study Demonstrates Superiority of Giroctocogene Fitelparvovec Over Routine Prophylaxis
Pfizer (PFE) recently announced encouraging results from the Phase 3 AFFINE study (NCT04370054), evaluating giroctocogene fitelparvovec, an investigational gene therapy, for adults with moderately severe to severe hemophilia A. This pivotal study underscores the transformative potential of gene therapy in providing effective bleed protection and reducing the treatment burden for patients.
Promising Efficacy and Safety Results
The AFFINE study met its primary objective, demonstrating both non-inferiority and superiority in total annualized bleeding rate (ABR) compared to routine Factor VIII (FVIII) replacement prophylaxis. Patients receiving a single 3e13 vg/kg dose of giroctocogene fitelparvovec showed a statistically significant reduction in mean total ABR from 4.73 pre-infusion to 1.24 post-infusion (one-sided p-value=0.0040).
Moreover, key secondary endpoints were achieved, further highlighting the superiority of giroctocogene fitelparvovec. An impressive 84% of participants maintained FVIII activity above 5% at 15 months post-infusion (one-sided p-value = 0.0086), with most participants reaching FVIII activity levels of at least 15%. Additionally, the mean treated ABR saw a dramatic reduction of 98.3%, from 4.08 pre-infusion to just 0.07 post-infusion (one-sided p-value < 0.0001). Notably, only one participant (1.3%) resumed prophylaxis post-infusion.
Safety Profile and Tolerability
Giroctocogene fitelparvovec was generally well tolerated in the AFFINE study. While 49.3% of participants experienced transient elevated FVIII levels ≥150%, these occurrences did not impact the therapy’s efficacy or safety. Serious adverse events were reported in 15 patients (20%), with 13 events in 10 patients (13.3%) deemed related to the treatment. These adverse events typically resolved with appropriate clinical management.
Professor Andrew Leavitt M.D., AFFINE lead investigator and Director of the Adult Hemophilia Treatment Center at the University of California, San Francisco, remarked, “The physical and emotional burden of frequent IV infusions or injections cannot be underestimated for people with hemophilia A. These positive results from the AFFINE trial show the transformative potential of giroctocogene fitelparvovec in providing superior bleed protection while easing the treatment burden.”
A Glimpse into the Future of Hemophilia A Treatment
Giroctocogene fitelparvovec represents a novel, investigational gene therapy combining a bio-engineered AAV6 capsid with a modified B-domain deleted human coagulation FVIII gene. The goal is to enable patients to produce FVIII endogenously following a single infusion, thereby offering long-term bleed protection and significantly reducing the need for routine prophylaxis with IV infusions or injections.
Dr. James Rusnak, Senior Vice President, Chief Development Officer of Internal Medicine and Infectious Diseases at Pfizer, expressed his enthusiasm for the AFFINE study results. “We are very pleased with the positive outcomes from the Phase 3 AFFINE study, demonstrating the safety and efficacy of our one-time gene therapy candidate for hemophilia A. We look forward to advancing this innovation to address the medical and treatment burden associated with frequent IV infusions or injections.”
Participants in the AFFINE study initially enrolled in a lead-in study (NCT03587116) and, upon successful completion, received a one-time dose of giroctocogene fitelparvovec by IV infusion. Patients will be evaluated over five years, with long-term follow-up extending up to 15 years.
Regulatory Pathways and Future Prospects
Further analyses of the full Phase 3 dataset are ongoing, and additional data will be presented at upcoming medical conferences. Giroctocogene fitelparvovec has received Fast Track and Regenerative Medicine Advanced Therapy designations from the U.S. FDA, along with Orphan Drug designations in the U.S. and the EU. Pfizer will engage with regulatory authorities in the coming months to discuss these promising results.
Pfizer’s commitment to advancing hemophilia treatment is evident with its recent FDA approval of BEQVEZ™ (fidanocogene elaparvovec) for hemophilia B and ongoing regulatory reviews for marstacimab, a novel subcutaneous therapy for hemophilia A and B. The successful development of giroctocogene fitelparvovec could mark a significant milestone in improving the quality of life for people living with hemophilia A.
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