Investigational Gene Therapy for Hemophilia A Shows Positive Results in Phase III Clinical Trial

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Giroctocogene fitelparvovec, an investigational gene therapy for the treatment of adults with moderately severe to severe hemophilia A has returned positive results in the Phase III AFFINE clinical trial (NCT04370054). Pfizer’s potential therapy achieved the trial’s primary objective of non-inferiority, as well as superiority, of total annualized bleeding rate (ABR) from week 12 through at least 15 months of follow up post-infusion compared with routine Factor VIII (FVIII) replacement prophylaxis treatment.¹

The Phase III AFFINE study is an open-label, multicenter, single-arm trial to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in adult male participants with moderately severe to severe hemophilia A. Participants in this study were initially enrolled in a lead-in study (NCT03587116). Upon successful completion, they were enrolled into the AFFINE trial where they received a one-time 3e13 vg/kg dose of giroctocogene fitelparvovec by IV infusion.

In achieving the primary endpoint, giroctocogene fitelparvovec, following a single dose, demonstrated 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). The trial met its key secondary endpoints as well, with 84% of participants maintaining FVIII activity >5% at 15 months post-infusion (one-sided p-value = 0.0086). 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 [15-44 months]; one-sided p-value < 0.0001).

“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,” Professor Andrew Leavitt MD, AFFINE lead investigator, departments of laboratory medicine and medicine division of hematology/oncology director, adult hemophilia treatment center, University of California, San Francisco, CA said 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.”

According to the United States Centers for Disease Control and Prevention, as many as 33,000 males are estimated to be living with hemophilia in the US. Among all males with hemophilia, just over 4 in 10 have the severe form of the bleeding disorder.²

“We are very pleased with these positive results from the Phase III AFFINE study demonstrating the safety and efficacy of our one-time gene therapy candidate for people with hemophilia A,” James Rusnak, MD, PhD, senior vice president, chief development officer, internal medicine and infectious diseases, research and development, Pfizer said 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.”

Pfizer plans on sharing additional data from the AFFINE study at an upcoming medical conference and will discuss these data with regulatory authorities in the coming months. Giroctocogene fitelparvovec has been granted Fast Track and Regenerative Medicine Advanced Therapy designations from the FDA and Orphan Drug designations in the US and European Union.

References

1. Pfizer Announces Positive Topline Results From Phase 3 Study of Hemophilia A Gene Therapy Candidate. News release. Pfizer. July 24, 2024. Accessed July 25, 2024. https://www.businesswire.com/news/home/20240724525239/en

2. Data and Statistics on Hemophilia. US Centers for Disease Control and Prevention. Accessed July 25, 2024. https://www.cdc.gov/hemophilia/data-research/index.html#:~:text=Key%20findings,Incidence%20and%20Prevalence%E2%80%8E