Abstract
INTRODUCTION Etranacogene dezaparvovec (ED, Hemgenix®) is a gene therapy approved by European Medicines Agency (EMA) in 2023 for adult patients with severe or moderately severe haemophilia B (HB) (FIX ≤2%) without inhibitors. In Spain, it became available in 2024 following approval by the Interministerial Commission. At present, no national referral network for infusion centers has been established. To date, only one patient in Spain has received this treatment. ED is expected to provide a functional cure for HB by enabling long-term endogenous FIX production after a single intravenous administration.
OBJECTIVE To report the initial clinical experience and outcomes in the first patient treated with ED in Spain
MATERIAL AND METHODS Clinical data were collected from the electronic medical record of the patient and follow-up laboratory reports.
RESULTS A 41-year-old male with moderately severe HB (baseline FIX 1.8%) was on prophylaxis with eftrenonacog alfa (50 IU/kg weekly). He had no current or previous history of inhibitors to FIX. The patient presented with advanced hemophilic arthropathy (HEAD-US score 7), predominantly in the ankles and right elbow. He had a history of HCV infection, now resolved. Liver stiffness measured by Fibroscan was 3.1 kPa. Anti-AAV5 antibody titers were <18.5 (AAV5 NAb Test Precission for Medicine®). On June 18th, 2025, ED was administered at a dose of 2×10¹³ gc/kg intravenously over one hour. Infusion was well tolerated, with no adverse events reported. Prophylaxis was discontinued the same day. The patient was discharged four hours post-infusion, with initiation of weekly follow-up visits according to product's summary of characteristics. From week 1 to week 4 post-infusion, FIX activity progressively increased from 13% to 31.6% (measured by one-stage coagulation assay, HemosIL SynthASil®, ACLTop®). ALT levels remained within normal range during this period. At week 4, ALT was 51 IU/L (ULN: 40 IU/L), while AST, total bilirubin, and CPK remained normal. Forty-eight hours later, ALT decreased to 41 IU/L; FIX was 28.3%. Four days later, ALT increased again to 48 IU/L, with a slight decrease in FIX to 26.9% (15% decline from peak). Based on our protocol and clinical trial data (HOPE-B), prednisone 60 mg/day was initiated. After 7 days (week 6), ALT normalized and FIX rose to 37.7%. Prednisone (PDN) was then tapered to 40 mg/day, maintaining weekly clinical and laboratory monitoring. 7 days after, ALT level is the same and FIX:C 42%, We decide a conservative and acceptable approach: maintain PDN at 40 mg/day, 7 days more, due to previous ALT fluctuations.
CONCLUSION Although follow-up is still short, ED administration has thus far been successful. The patient reported a high degree of satisfaction, despite the demanding monitoring schedule during the first months. Long-term durability of FIX expression is expected, based on data from pivotal trials (Shah J. Curr Med Res Opin. 2022. DOI: 10.1080/03007995.2022.2133492), and recent 5-year follow-up reports from HOPE-B showing sustained FIX activity (~45.7%) without safety concerns (von Drygalski A. Blood Adv. 2025. DOI: 10.1182/bloodadvances.2024015291). In our case, the patient's evolution follows the expected pattern: good initial response, mild and reversible liver enzyme elevation with use of prednisone, and satisfactory FIX levels. Immunosuppression is being adapted to clinical and laboratory evolution. We expect to present updated 6-month data at the ASH 2025 Congress.
