Pfizer’s investigational haemophilia B gene therapy candidate, fidanacogene elaparvovec, has shown promising top-line results in a phase 3 trial of adult male patients with moderately severe to severe haemophilia B.
The BENEGENE-2 study met its primary endpoint of non-inferiority and superiority in the annualised bleeding rate (ABR) of total bleeds after a single intravenous (IV) infusion of fidanacogene elaparvovec versus prophylaxis regimen with factor IX, administered as part of usual care.
The results showed superiority, with a mean ABR for all bleeds of 1.3 for the 12 months from week 12 to month 15 compared to an ABR of 4.43 during the lead-in pre-treatment period of at least six months, demonstrating a 71% reduction in ABR.
Key secondary endpoints were also met, with a 78% reduction in treated ABR and a 92% reduction in annualised infusion rate. The candidate was generally well-tolerated, according to the company, with a safety profile consistent with phase 1/2 results.
Haemophilia B is a genetic bleeding disorder resulting from missing or insufficient levels of blood clotting factor IX, a protein needed to produce blood clots to stop bleeding.
Patients with moderate-to-severe haemophilia B typically require a routine treatment regimen of IV infusions of factor IX replacement products to maintain sufficient levels of clotting factor to prevent bleeding episodes.
While these therapies are effective, patients must adhere to strict, lifelong infusion schedules and may also continue to experience spontaneous bleeding episodes as well as limited mobility, joint damage or severe pain as a result of the disease.
Pfizer hopes its gene therapy candidate could allow appropriate patients living with haemophilia B to produce their own factor IX, after a one-off, single dose by IV infusion.
“The burden of people living with haemophilia B face is significant, with many receiving routine infusions or injections that can interfere with their ability to take part in day-to-day activities that many take for granted,” said Adam Cuker, director, Penn Comprehensive and Hemophilia Thrombosis Program.
He continued: “The BENEGENE-2 data demonstrates the promise of this gene therapy candidate as a potential one-time option for people living with haemophilia B as a means of reducing the clinical and treatment burden over the long term.”
In November last year, the US Food and Drug Administration approved CSL Behring’s Hemgenix (etranacogene dezaparvovec) as the first gene therapy for adult patients with haemophilia B.