Pfizer Reports Positive Phase 3 Results for Hemophilia A Gene Therapy

Pfizer Inc. has announced promising results from its Phase 3 AFFINE study, which evaluated giroctocogene fitelparvovec, an investigational gene therapy for adults suffering from moderately severe to severe hemophilia A. The study has shown that giroctocogene fitelparvovec meets both its primary and key secondary objectives, demonstrating superiority compared to routine Factor VIII (FVIII) replacement prophylaxis treatment.

The primary objective of the AFFINE study was to achieve non-inferiority and superiority in reducing the total annualized bleeding rate (ABR) from Week 12 over at least 15 months post-infusion compared to conventional FVIII replacement therapy. The results revealed a significant reduction in mean total ABR from 4.73 pre-infusion to 1.24 post-infusion, with a one-sided p-value of 0.0040.

Secondary endpoints of the trial also supported the gene therapy's superiority over prophylaxis. A substantial 84% of participants maintained FVIII activity levels above 5% at 15 months post-infusion, with many reaching levels of 15% or higher. Furthermore, the mean treated ABR dropped drastically by 98.3%, from 4.08 in the pre-infusion period to 0.07 post-infusion, demonstrating the efficacy of the single-dose therapy. Throughout the study, only one participant (1.3%) returned to prophylaxis treatment after receiving giroctocogene fitelparvovec.

Regarding safety, giroctocogene fitelparvovec was generally well tolerated among participants. Some transient elevated FVIII levels ≥150% were observed in 49.3% of the treated group, but these did not affect the overall efficacy or safety outcomes. Serious adverse events were reported in 20% of the patients, with 13 of these events considered treatment-related. Nevertheless, these adverse events were typically managed effectively through clinical interventions.

Dr. Andrew Leavitt, the lead investigator of the AFFINE study, expressed his optimism about the potential of giroctocogene fitelparvovec to transform hemophilia A treatment. Dr. Leavitt highlighted the significant reduction in treatment burden and superior bleed protection provided by the gene therapy compared to routine FVIII prophylaxis.

Giroctocogene fitelparvovec is an innovative gene therapy that employs a bio-engineered AAV6 capsid containing a modified B-domain deleted human coagulation FVIII gene. The therapy aims to enable patients with hemophilia A to produce FVIII autonomously for extended periods, thereby reducing the need for regular intravenous infusions or injections.

Dr. James Rusnak, Pfizer's Senior Vice President and Chief Development Officer of Internal Medicine and Infectious Diseases Research and Development, voiced his satisfaction with the positive outcomes of the AFFINE study. He emphasized Pfizer's ongoing commitment to alleviating the medical and treatment burdens associated with frequent and time-consuming IV infusions for hemophilia patients.

Participants in the Phase 3 AFFINE study were initially enrolled in a lead-in study and, upon meeting the criteria, received a single 3e13 vg/kg dose of giroctocogene fitelparvovec via IV infusion. The study is designed to follow participants over five years, with a potential extended follow-up of up to 15 years.

The complete dataset from the AFFINE study is still under analysis, and further details will be shared at future medical conferences. Giroctocogene fitelparvovec has received various designations from the U.S. Food and Drug Administration (FDA), including Fast Track and Regenerative Medicine Advanced Therapy, as well as Orphan Drug status in both the U.S. and the European Union. Pfizer plans to engage with regulatory authorities soon to discuss these promising results.

This gene therapy marks a significant step forward in Pfizer's ongoing efforts to innovate hemophilia treatment, adding to their recent FDA approval of BEQVEZ™ (fidanocogene elaparvovec) for hemophilia B and their regulatory submissions for marstacimab, a potential novel subcutaneous therapy for hemophilia A and B.