Pfizer Inc. has reported encouraging topline results from the Phase 3 AFFINE study (NCT04370054). This study evaluates giroctocogene fitelparvovec, an investigational gene therapy aimed at treating adults with moderately severe to severe hemophilia A.
In the trial, 75 men with moderately severe to severe hemophilia A were initially enrolled in a lead-in study and received routine FVIII replacement therapy for six months. They then entered the open-label, single-arm Phase III AFFINE study, receiving a one-time intravenous dose of the gene therapy.
Giroctocogene fitelparvovec utilizes a bioengineered adeno-associated virus serotype 6 capsid to deliver a modified B-domain deleted FVIII gene, addressing the FVIII deficiency in hemophilia A. Patients who received the therapy experienced a significant reduction in their average total annualized bleeding rate (ARB), dropping to 1.24 from week 12 through at least 15 months of follow-up, compared to an average total ARB of 4.73 during the lead-in period with FVIII replacement therapy.
Most patients maintained mild to normal levels of FVIII activity post-treatment, with only one participant returning to prophylaxis. The gene therapy was generally well tolerated, with serious adverse events observed in 15 patients; 13 events in 10 patients were related to the treatment and generally resolved with clinical management.
Giroctocogene fitelparvovec was initially developed by Sangamo Therapeutics, which transferred the manufacturing technology and investigational new drug application to Pfizer in 2019. Pfizer oversees pivotal studies, regulatory activities, and potential global commercialization. Sangamo is eligible for up to $220 million from Pfizer in milestone payments and royalties.
Hemophilia is a rare inherited bleeding disorder where a deficiency in clotting factor VIII (FVIII) causes prolonged bleeding. It affects approximately 25 in 100,000 male births worldwide, with 55-75% of cases being moderate to severe. People with hemophilia A face a higher risk of spontaneous bleeding, as well as bleeding following injuries or surgery. This lifelong condition requires continuous monitoring and therapy to manage bleeding episodes and prevent complications. The severity of hemophilia A is determined by the amount of FVIII in the blood, with lower levels increasing the likelihood of serious health problems due to excessive bleeding.
Earlier this year, Pfizer’s gene therapy for hemophilia B, Beqvez (fidanacogene elaparvovec), was approved by the US FDA and Health Canada and is awaiting a decision from the European Medicines Agency.
