Three months after scoring FDA approval for a hemophilia B gene therapy, Pfizer has posted phase 3 data suggesting it may be able to pull off the same success with a different candidate in hemophilia A.
The therapy in question, giroctocogene fitelparvovec, was first developed at Sangamo Therapeutics and has now demonstrated superiority to standard-of-care for adults with the bleeding disorder.
Hemophilia A is caused by insufficient levels of a blood protein called factor VIII, and current treatment normally involves patients receiving regular infusions of this protein. Pfizer’s hope for giroctocogene fitelparvovec, which contains a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation FVIII gene, is that a single infusion of the therapy will allow patients to produce factor VIII for themselves “for an extended period time.”
Judging by the data from 50 patients with moderately severe to severe hemophilia A who participated in the phase 3 AFFINE study, the pharma is on the right track. These patients received six months of routine prophylaxis treatment before receiving a single dose of giroctocogene fitelparvovec, after which they were monitored for 15 months.
Pfizer was able to demonstrate a “statistically significant” mean reduction in annualized bleed rate (ABR) as a result of taking the gene therapy—1.24 compared to a rate of 4.73 before they received giroctocogene fitelparvovec—hitting the trial’s primary endpoint.
The study also hit its key secondary endpoints, including 84% of participants maintaining factor VIII activity of more than 5% above their pre-dosed level. Only one of the monitored patients returned to using factor VIII infusion within the 15 month period, Pfizer noted.
But Pfizer did not, however, provide data on how long the treatment effect will last, a key question for a modality that can only be dosed once.
Giroctocogene fitelparvovec was generally well tolerated in the trial, said Pfizer, with 15 patients (20%) reporting serious adverse events, of which 13 events were considered to be treatment-related. These treatment-related events were “generally resolved in response to clinical management,” the pharma said.
The gene therapy has already received fast-track and regenerative medicine tags from the FDA, and Pfizer said this morning that the phase 3 data will be discussed with regulators “in the coming months.”
“We are very pleased with these positive results from the phase 3 AFFINE study demonstrating the safety and efficacy of our one-time gene therapy candidate for people with hemophilia A,” James Rusnak, M.D., Ph.D., senior vice president, chief development officer, Internal Medicine and Infectious Diseases, Research and Development, said in this morning’s 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,” Rusnak added.
The phase 3 win continues a busy year for Pfizer’s hemophilia pipeline. In April, the pharma scored FDA approval for fidanacogene elaparvovec-dzkt, marketed as Beqvez, for adults with the bleeding disorder hemophilia B. Not only did this mark the first FDA-approved gene therapy for Pfizer, but it was also the second-ever gene therapy to get the nod for the indication, following in the wake of CSL and uniQure’s Hemgenix.
Should Pfizer manage the same feet in hemophilia A with giroctocogene fitelparvovec, it will be following in the path of BioMarin, which received approval for its gene therapy Roctavian in 2023. The therapy has stumbled on the market and BioMarin is now considering a divestiture of the asset. Just four patients had been treated across Europe and the U.S. as of April, despite having approvals in both regions. That added up to sales of just $800,000.
Pfizer will need to show in future data releases that giroctocogene fitelparvovec can outlast the competitor on durability.
It’s not been a totally smooth path through the clinic for giroctocogene fitelparvovec, with the AFFINE trial being put on temporary hold by the FDA a couple of a years ago due to some patients experiencing factor VIII activity greater than 150%, which is considering the upper limit of normal levels.
Pfizer said today that transient elevated factor VIII levels of 150% or greater were observed in half of the dosed participants in the trial, but this had “no impact on efficacy and safety results.”
The fourth quarter of this year will also see the FDA make a call on whether to approve Pfizer’s human monoclonal immunoglobulin G isotype marstacimab to treat both hemophilia A and B.