Pfizer saw positive topline results of its investigational gene therapy for adults with hemophilia A in a Phase III study (AFFINE). The therapy, giroctocogene fitelparvovec, reduced patients’ bleeds for at least 15 months and was generally well tolerated. It comprises a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation FVIII gene. The big question is, how long will those effects last?
Pfizer recently received FDA approval for BEQVEZ (fidanocogene elaparvovec), a “one and done” gene therapy treatment for hemophilia B.
“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 professor Andrew Leavitt, MD, AFFINE lead investigator, department of laboratory medicine and the medicine division of hematology/oncology director, Adult Hemophilia Treatment Center, University of California, San Francisco, CA.
The hope is that a single infusion of giroctocogene fitelparvovec may allow patients to produce FVIII themselves for an extended period of time, providing bleed protection and reducing the need for routine prophylaxis with intravenous (IV) infusions or injections.
The AFFINE study achieved its 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. Following a single dose, giroctocogene fitelparvovec demonstrated a statistically significant reduction in mean total ABR compared to the pre-infusion period.
The trial’s key secondary endpoints were also met, and the treatment demonstrated superiority compared to prophylaxis. 84% of participants maintained FVIII activity >5% at 15 months post-infusion, with the majority of participants having FVIII activity ≥15%.
“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 VP, internal medicine and infectious diseases, research and development, Pfizer.
Eligible study participants were initially enrolled in a lead-in study (NCT03587116) and upon successful completion, they went into the AFFINE study where they received a one-time dose of giroctocogene fitelparvovec by IV infusion. They were screened with a validated assay designed to identify individuals who test negative for neutralizing antibodies to the gene therapy vector. Clinical study participants will be evaluated in AFFINE over the course of five years, and up to a total of 15 years as part of a long-term follow-up study.
Analyses of the full Phase III dataset from the AFFINE study are ongoing and additional data will be presented at upcoming medical meetings. Giroctocogene fitelparvovec has been granted Fast Track and Regenerative Medicine Advanced Therapy designations from the FDA, as well as Orphan Drug designations in the U.S. and the European Union. Pfizer will discuss these data with regulatory authorities in the coming months.
BEQVEZ (fidanocogene elaparvovec), Pfizer’s hemophilia B gene therapy, allows patients to produce factor IX (FIX), which is the enzyme they are born missing. The current standard of care for this condition requires regular intravenous infusions of FIX that are often administered multiple times a week or multiple times a month.
