Pfizer Reveals Successful Phase 3 Outcomes for Hemophilia A Gene Therapy Candidate
Thursday, July 25, 2024
Pfizer Inc. (NYSE: PFE) has released positive topline results from the Phase 3 AFFINE study (NCT04370054), which tested giroctocogene fitelparvovec, a gene therapy for adults with moderately severe to severe hemophilia A.
The study met its primary and secondary endpoints. Giroctocogene fitelparvovec showed both non-inferiority and superiority compared to standard Factor VIII (FVIII) replacement therapy. After a single dose of 3e13 vg/kg, participants experienced a statistically significant reduction in the mean total annualized bleeding rate (ABR) from 4.73 to 1.24 (one-sided p-value = 0.0040).
Key secondary endpoints also demonstrated positive outcomes. At 15 months post-infusion, 84% of participants had FVIII activity levels greater than 5% (one-sided p-value = 0.0086), with most achieving levels of 15% or higher. The mean ABR showed a substantial 98.3% reduction from 4.08 before infusion to 0.07 after (one-sided p-value < 0.0001). Only one participant (1.3%) needed to resume prophylactic treatment post-infusion.
The therapy was generally well tolerated, with transient elevated FVIII levels ≥150% seen in nearly half of the participants, though these did not impact the efficacy or safety outcomes. Serious adverse events occurred in 15 patients (20%), with 13 events reported by 10 patients (13.3%) linked to the treatment. These events were managed and resolved effectively.
Professor Andrew Leavitt, the AFFINE study’s lead investigator, highlighted the significant potential of giroctocogene fitelparvovec to enhance treatment for hemophilia A patients by providing superior bleeding protection and reducing the need for frequent infusions.
Giroctocogene fitelparvovec utilizes a bio-engineered AAV6 capsid and a modified human FVIII gene. The aim is for a single infusion to enable patients to produce FVIII on their own for an extended period, potentially eliminating the need for regular prophylaxis.
Pfizer, expressed satisfaction with the results and anticipation for the therapy’s future. Pfizer plans to discuss these findings with regulatory bodies soon.
Pfizer has also recently gained FDA approval for BEQVEZ™ (fidanocogene elaparvovec) for hemophilia B and is awaiting decisions on marstacimab, a potential new subcutaneous therapy for hemophilia A and B.
The AFFINE study, an open-label, multicenter trial, involved 75 adult male participants with moderately severe to severe hemophilia A. Participants received a single dose of giroctocogene fitelparvovec after completing a lead-in study. The study will continue to monitor participants for up to 15 years.
This gene therapy is developed in collaboration with Sangamo Therapeutics, which transferred the relevant technology and Investigational New Drug application to Pfizer. Pfizer now manages the pivotal studies, regulatory processes, and potential commercialization.
Hemophilia A is a rare genetic disorder where a deficiency in clotting factor VIII leads to prolonged bleeding. It affects about 25 in every 100,000 male births globally, with 55-75% of those affected having moderate to severe forms of the condition. Management of the disease involves ongoing treatment to control bleeding risks.
Source: businesswire.com
