Safety and efficacy of etranacogene dezaparvovec: the safety and efficacy of this medicine were evaluated in 2 clinical studies: a phase 2b study [31] and a phase 3 study [21,41]. In both studies, adult male patients (body weight range: 58 to 169 kg) with moderately severe or severe hemophilia B (FIX activity ≤2%) were studied, a total of 57 patients. These patients were all on prophylactic treatment with clotting factor IX. They received a single gene therapy administration, into a vein, after which they are followed up for 5 years.
Evaluation of the safety of etranacogenic dezaparvovec in these studies
Like any medicine, this medicine can cause side effects, although not everybody gets them. The side effects were observed in the clinical studies with etranacogene dezaparvovec:
Very common (occur in more than 1 in 10 patients)
- headache
- increase of the liver enzyme alanine aminotransferase (ALT) in the blood
- increase of the liver enzyme aspartate aminotransferase (AST) in the blood
- flu-like illness
- increase of the concentration of C-reactive protein (CRP), an inflammation marker, in the blood
- infusion reaction: allergic reactions (hypersensitivity), reaction at the infusion site, dizziness, itchy eyes (pruritus), reddening of the skin (flushing), upper abdominal pain, itchy skin rash (urticaria), chest discomfort and fever
Common (occur in less than 1 in 10 patients)
- dizziness
- nausea
- fatigue
- general feeling of being unwell (malaise)
- increased blood levels of bilirubin, a yellow breakdown product of red blood cells
- increased blood levels of creatine kinase, an enzyme (protein) found mainly in the heart, brain, and skeletal muscles
Of the 54 patients, 1 received a partial dose (10% of the recommended dose) as a result of an infusion reaction during administration, and one patient who was 75 years old at the start of the study died 15 months after the administration of etranacogene dezaparvovec due to cardiogenic shock, which was confirmed to be unrelated to the gene therapy.
In both studies, no patient has developed a FIX inhibitor (or FIX-neutralizing antibody) to date.
Efficacy of etranacogenic dezaparvovec in these studies
The phase 3 study in 54 patients:
What the researchers wanted to investigate in this study was a reduction in the total number of bleedings per year (the ‘ABR’ (annual bleeding rate)) compared to the period before treatment with this gene therapy. Between month 7 after administration and 2 years after administration, the average number of bleedings per year decreased from 4.19 to 1.51, a reduction of 64%. The average number of joint bleedings decreased from 2.14 to 0.32, and the number of spontaneous bleedings also decreased significantly.
The FIX activity in the blood of the participating patients increased from an average of 1.19 IU/dL at the start of the study to 36.7 IU/dL 2 years after administration.
21 Pipe SW, Leebeek FWG, Recht M, Key NS, Castaman G, Miesbach W, et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. New Engl J Med. 2023;388(8):706–18.
31 Drygalski A von, Steven P. Stable and durable factor IX levels in hemophilia B patients over 3 years post etranacogene dezaparvovec gene therapy. Blood Advances. 2022
41 Coppens M et al. Lancet Haematol 2024 ; 11 (4) : e265-e275 Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B) : 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial