FDA Lifts Hold on Phase 3 Trial of Gene Therapy SB-525 for Hem A
The U.S. Food and Drug Administration (FDA) has lifted a clinical hold on the Phase 3 trial testing the safety and effectiveness of SB-525 (giroctocogene fitelparvovec), an experimental gene therapy for hemophilia A.
The FDA placed the clinical hold late last year after Pfizer voluntarily paused patient screening and dosing in the AFFINE trial (NCT04370054), a multicenter study evaluating the safety and efficacy of a single infusion of SB-525 in about 63 men, ages 18–64, with moderate to severe hemophilia A.
The therapy is designed to deliver a healthy copy of the gene that carries instructions to make factor VIII (FVIII), the blood-clotting protein that is missing or is defective in people with hemophilia A.
Some treated patients showed elevated levels of FVIII in their bloodstream beyond 150% of normal, which raises the risk of blood clots.
Along with the lifting of the clinical hold, Pfizer also disclosed that a trial participant experienced deep vein thrombosis in the leg — when a blood clot forms in a deep vein — accompanied by elevated levels of FVIII.
According to the company, the participant had a history of blood clots before entering the trial, a known risk factor for subsequent events, and should have been excluded from the study.
The case was followed up to determine all factors that might have contributed to the clots, including missed doses of anticoagulants (blood thinners) prescribed by investigators. Pfizer shared the information with study researchers, health authorities, and an external data monitoring committee. The patient was reported to be fairing well.
Although the FDA has lifted the hold, the voluntary pause in dosing new patients remains in place. Pfizer will continue to meet with regulators about the necessary conditions to restart the trial, including approval of updated study protocols.
SB-525 is a one-time treatment administered directly into the bloodstream. The primary outcome of the Phase 3 trial is to assess changes in the annualized bleeding rate over one year.
FVIII activity and the use of FVIII replacement therapies will also be assessed as secondary measures. Participants will be followed for five years to record the incidence and severity of adverse events.
SB-525 is also being evaluated in the ongoing Phase 1/2 Alta trial (NCT03061201) in men with severe hemophilia A. As previously reported, a single dose of the gene therapy increased FVIII levels and prevented bleeds and the need for preventive treatment for at least two years.
The gene therapy received fast track, orphan drug, and regenerative medicine advanced therapy designations in the U.S. and orphan medicinal product status in Europe.