Pfizer Gene Therapy for Hemophilia A Patients Shows Promising Results in Study

A Phase III study (AFFINE) has achieved its primary objective of not only non-inferiority but also superiority of total annualized bleeding rate (ABR) using giroctocogene fitelparvovec, an investigational gene therapy for adults with moderately severe to severe hemophilia A, from week 12 up to at least 15 months of follow-up post-infusion, when compared to routine Factor VIII (FVIII) replacement prophylaxis, Pfizer announced on July 24, 2024 (1,2).

A single dose of giroctocogene fitelparvovec, according to a Pfizer press release that summarized the findings of the study, yielded a statistically significant reduction in mean total ABR when measured against the pre-infusion period.

Giroctocogene fitelparvovec contains a bioengineered adeno-associated virus type 6 (AAV6) capsid and modified B-domain deleted human coagulation FVIII gene (1). The goal of treating hemophilia A patients with this therapy is to allow them to produce FVIII on their own for a certain period of time following a single infusion—which, in turn. offers bleed protection as well as a reduced need for routine prophylaxis with intravenous (IV) injections or infusions.

Hemophilia A, which occurs in approximately 25 of every 100,000 male births worldwide, is an inherited disorder causing those who are affected to bleed for longer than the normal amount of time because of a deficiency in the protein required for blood clotting (1). Anywhere from 55% to 75% of cases in males can be classified as moderate to severe, carrying with them increased risk of spontaneous bleeding or bleeding after injuries or surgery, and lifelong monitoring and therapy, among other potential health problems.

“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,” Andrew Leavitt, MD, AFFINE lead investigator and director of the departments of laboratory medicine and medicine division of hematology/oncology at the Adult Hemophilia Treatment Center, University of California, said in the 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.”

“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,” said James Rusnak, MD, PhD, senior vice-president and 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.”

Analyses of the full dataset from the Phase III study are still ongoing, with additional data to be presented at future medical meetings.

References

1. Pfizer Inc. Pfizer Announces Positive Topline Results from Phase 3 Study of Hemophilia A Gene Therapy Candidate. Press Release, July 24, 2024.
2. National Library of Medicine. Study to Evaluate the Efficacy and Safety of PF-07055480 /​ Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (AFFINE). ClinicalTrials.gov, July 24, 2024 (accessed July 24, 2024).