A single dose of giroctocogene fitelparvovec significantly reduced the mean total annual bleeding rate in patients with moderately severe to severe hemophilia A.
Topline results from the Phase III AFFINE study showed the efficacy of giroctocogene fitelparvovec in treating adults with moderately severe to severe hemophilia A. The investigational gene therapy demonstrated both non-inferiority and superiority in reducing the total annualized bleeding rate (ABR) from week 12 through at least 15 months post-infusion compared to standard Factor VIII (FVIII) prophylaxis. According to Pfizer, the therapy reduced the mean total ABR from 4.73 to 1.24 (one-sided p-value=0.0040) through a single 3e13 vg/kg dose.1
“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 AFFINE lead investigator Andrew Leavitt, MD, departments of laboratory medicine, medicine division of hematology/oncology director, adult hemophilia treatment center, University of California, San Francisco, CA, in a press 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.”
The open-label, multicenter, single-arm AFFINE study evaluated the efficacy and safety of a single infusion of giroctocogene fitelparvovec in 75 adult male participants with moderately severe to severe hemophilia A. The primary endpoint of the study was the non-inferiority and superiority of giroctocogene fitelparvovec in reducing total ABR compared to FVIII prophylaxis. Of the 75 patients, 50 completed a minimum six months of routine FVIII replacement prophylaxis therapy during the lead-in study.
Results show that 84% of participants maintained FVIII activity >5% at 15 months post-infusion, with a major 98.3% reduction in the mean treated ABR from 4.08 to 0.07. According to the company, one participant returned to prophylaxis post-infusion.
Giroctocogene fitelparvovec was reported to be well tolerated in the AFFINE study, with transient elevated FVIII levels reported in 49.3% of dosed participants. This had no impact on efficacy and safety results of the study. Serious adverse events (AEs) were found in 20% of patients, including 10 patients experiencing AEs related to treatment.1
According to the Centers for Disease Control and Prevention (CDC), approximately 33,000 males in the United States are currently living with hemophilia. While exact numbers are currently unknown, hemophilia A is three to four times as common as hemophilia B. Further, the median age at diagnosis is 36 months for individuals with mild hemophilia, eight months for those with moderate hemophilia, and one month for individuals with severe hemophilia. In two-thirds of all cases, there has been a family history of hemophilia. For the other third, diagnoses are commonly made when an unusual bleeding event occurs.2
“We are very pleased with these positive results from the Phase 3 AFFINE study demonstrating the safety and efficacy of our one-time gene therapy candidate for people with hemophilia A,” said James Rusnak, MD, PhD, SVP, chief development officer, internal medicine and infectious diseases, research and development, Pfizer, in the press release. “We look forward to advancing this latest innovation to help address the medical and treatment burden associated with frequent and time-consuming IV infusions or injections, building on Pfizer’s more than 40-year effort to advance hemophilia treatment.”
Full analyses of the AFFINE trial are ongoing. Further data are expected to be presented at an upcoming medical meeting.1
References
1. Pfizer Announces Positive Topline Results From Phase 3 Study of Hemophilia A Gene Therapy Candidate. Pfizer. July 25, 2024. Accessed July 25, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-results-phase-3-study
2. Data and Statistics on Hemophilia. CDC. Accessed July 25, 2024. https://www.cdc.gov/hemophilia/data-research/index.html
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