Steven Pipe, MD, Professor of Pediatrics and Pathology, and Pediatric Medical Director of the Hemophilia and Coagulation Disorders Program at the University of Michigan, discusses the recent announcement of positive long-term results from the phase 3 HOPE-B clinical trial evaluating etranacogene dezaparvovec (EtranaDez), an investigational gene therapy for hemophilia B.
Hemophilia B is a congenital bleeding disorder due to dysfunction or deficiency of coagulation Factor IX (FIX). People with this condition may bleed for longer periods of time after injury or surgery. They are also susceptible to spontaneous bleeding in muscles, joints and organs, which can be extremely painful and, in some cases, life-threatening.
As Dr. Pipe explains, the current standard of care for hemophilia B includes life-long prophylactic infusions of FIX to temporarily replace or supplement low levels of the blood-clotting factor. While these infusions can significantly benefit these patients, infusions are inconvenient, painful, and can cause veins to fibrose over time, which makes the treatment more difficult. A patient’s immune system may also generate inhibitors against the replacement factor, negating the treatment benefit. Additionally, prophylactic FIX replacement therapy sometimes fails to control unobservable micro-bleeds in the joints, meaning that the degeneration can continue despite regular infusions. As such, there is a need for novel therapeutic options for hemophilia B patients.
Etranacogene dezaparvovec is an investigational adeno-associated virus five (AAV5)-based gene therapy for people living with hemophilia B.
In the phase 3 HOPE-B trial, 54 adult hemophilia B patients classified as severe or moderately severe and requiring prophylactic FIX replacement therapy were enrolled. After the six-month lead-in period in which patients continued their current standard of care therapy to establish baseline ABR, patients received a single intravenous administration of etranacogene dezaparvovec. The primary endpoint in the pivotal HOPE-B study was 52-week ABR after achievement of stable FIX expression compared with the six-month lead-in period, considering all bleeds regardless of investigator adjudication as true bleeds. For this endpoint, ABR was measured from month seven to month 18 after infusion, ensuring the observation period represented likely steady-state FIX transgene expression. Secondary endpoints included assessment of FIX activity and statistical superiority of ABR after dosing.
The final data from the HOPE-B trial were recently announced and demonstrated that etranacogene dezaparvovec produced mean FIX activity of 39.0 IU/dL at six months and 36.9 IU/dL at 18 months post infusion. For context, patients with severe hemophilia B often have less than 1.0 IU/dL and greater than 10.0 IU/dL is thought to be necessary for an absence of joint bleeding. After the six-month lead-in period post-infusion, the adjusted ABR for all bleeds was reduced by 64% (P = .0002) and all FIX-treated bleeds was reduced by 77% (3.65 to 0.83; P < .0001) over months 7 to 18. In addition, 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued use of prophylaxis, with an overall 97% reduction in mean unadjusted annualized FIX consumption of 257338.8 IU per year per participant to 8486.6 IU per year per participant (from lead-in period to months 13-18).
The data presented also suggests that etranacogene dezaparvovec is generally well-tolerated. The majority of adverse events (80.4%) in the study have been considered mild. Finally, there were statistically significant improvements in quality-of-life domains for patients in this study including “feelings”, “treatment”, “work/school”, and “future”.
To learn more about hemophilia B and other rare hematological disorders, visit checkrare.com/diseases/hematologic-disorders/
