Pfizer's investigational gene therapy, fidanacogene elaparvovec (SPK-9001), has demonstrated positive top-line results in the Phase 3 BENEGENE-2 study for the treatment of adult males with moderately severe to severe haemophilia B. The study met its primary endpoint, showing both non-inferiority and superiority in the annualized bleeding rate (ABR) compared to the standard prophylaxis regimen with Factor IX (FIX).
The BENEGENE-2 trial evaluated the efficacy and safety of a single dose of fidanacogene elaparvovec in reducing bleeding episodes in haemophilia B patients. Haemophilia B, a rare genetic disorder affecting primarily males, results from a deficiency in clotting factor IX, leading to prolonged bleeding. According to the World Federation of Hemophilia, over 38,000 individuals worldwide were living with haemophilia B in 2021.
Significant Reduction in Bleeding
The results of the BENEGENE-2 study indicated a substantial reduction in bleeding events following a single infusion of fidanacogene elaparvovec. The mean ABR for all bleeds was 1.3 during the 12-month period from week 12 to month 15 post-infusion, compared to an ABR of 4.43 during the pre-treatment period of at least six months. This represents a 71% reduction in ABR after a single dose of 5e11 vg/kg of the gene therapy.
Secondary Endpoints and Safety Profile
In addition to the primary endpoint, key secondary endpoints also showed significant improvements. There was a 78% reduction in treated ABR and a 92% reduction in the annualized infusion rate. The safety profile of SPK-9001 was generally well-tolerated, consistent with previous Phase 1 and Phase 2 studies. Participants in the clinical trial will continue to be monitored in a long-term study for up to 15 years.
Expert Commentary
Dr. Adam Cuker, director of the Penn Comprehensive and Hemophilia Thrombosis Program, highlighted the potential of fidanacogene elaparvovec to alleviate the burden faced by individuals with haemophilia B, noting that the 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."
Mechanism of Action
Fidanacogene elaparvovec (SPK-9001) is designed to enable patients with haemophilia B to produce their own Factor IX (FIX) after a single treatment, eliminating the need for regular exogenous FIX infusions. The therapy utilizes an adeno-associated virus (AAV) vector to deliver a high-activity human coagulation FIX gene to the patient's cells.
Regulatory Status and Future Plans
Fidanacogene elaparvovec has been granted breakthrough therapy designation, regenerative medicine advanced therapy (RMAT) designation, and orphan drug designation by the FDA, as well as PRIME and orphan drug designation by the EMA. Pfizer plans to present additional data from the BENEGENE-2 study at an upcoming scientific conference. The company is also conducting Phase 3 trials for gene therapies targeting haemophilia A and Duchenne muscular dystrophy and is investigating marstacimab, a potential subcutaneous therapy for haemophilia A and B.
