One-Time Gene Therapy Achieves Long-Term Bleeding Control in Hemophilia B
In a promising development for patients with hemophilia B, a one-time infusion of a gene therapy known as SPK-9001 has demonstrated sustained therapeutic benefits, dramatically reducing bleeding episodes and factor IX usage, according to clinical trial data published in the New England Journal of Medicine.
The investigational therapy utilizes an adeno-associated viral (AAV) vector carrying a high-specific-activity variant of factor IX—known as factor IX–R338L or Padua—engineered to produce levels of clotting factor sufficient to prevent spontaneous bleeding. This novel approach allows treatment at a low vector dose, potentially minimizing immune responses to the viral capsid, a known challenge in gene therapy.
The phase 1/2 trial, supported by Spark Therapeutics and Pfizer, enrolled 10 men with severe or moderately severe hemophilia B, all with baseline factor IX activity levels of 2% or lower. Participants received a single intravenous infusion of SPK-9001 at a dose of 5×10¹¹ vector genomes per kilogram. The team evaluated factor IX activity, bleeding frequency, and usage of clotting factor over a follow-up period ranging from 28 to 78 weeks.
The results showed that participants achieved durable expression of factor IX, with an average activity level of 33.7 ± 18.5%—within the range considered to prevent spontaneous bleeding. Bleeding episodes plummeted from a pre-treatment average of 11.1 events per year to just 0.4 events per year (P = .02). Factor IX concentrate usage similarly dropped from an average of 2908 IU/kg annually to only 49.3 IU/kg (P = .004). Notably, 8 of the 10 men ceased factor use entirely, and 9 of 10 experienced no bleeding after treatment.
Safety outcomes were encouraging as no serious adverse events were reported. Two participants experienced asymptomatic liver enzyme elevations, which were successfully managed with short-term prednisone. Importantly, no inhibitor formation or thrombotic events occurred, key safety considerations in gene therapy for bleeding disorders.
The authors note that the small sample size and relatively short follow-up underscore the need for larger, long-term studies to confirm these early findings and monitor ongoing safety.
Reference
George LA, Sullivan SK, Giermasz A, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 2017;377:2215-2227. doi:10.1056/NEJMoa1708538
