Etranacogene Dezaparvovec: 15-Month Follow-Up of the First Patient Infused in Spain

Etranacogene dezaparvovec is an adeno-associated viral vector gene therapy (GT) for severe and moderately severe haemophilia B. In Spain, it is reimbursed under a five-year outcomes-based payment agreement recorded on the public VALTERMED platform (Ministerio de Sanidad, Madrid, Spain).Real-world experience remains limited, and follow-up of liver events that appear late after the infusion is scarcer still.We report the complete 15-month course of the first patient treated commercially with this therapy in Spain.He was a 42-year-old man with moderately severe haemophilia B (baseline factor IX (FIX) activity 1.6 IU/dL), established haemophilic arthropathy, a Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score of 23, and cured hepatitis C. Neutralising antibodies against adeno-associated virus serotype 5 were undetectable.He had been on prophylaxis with recombinant factor IX linked to Fc at a dose of 60 IU/kg every seven days for six years, with a mean trough of 5.5% and an annualised bleeding rate of 1.66.He received a single intravenous infusion of 2 × 10¹³ genome copies (gc)/kg in 2025, stopping prophylaxis the following day.Monitoring was weekly during the first months, with FIX, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine phosphokinase (CPK) measured in the same laboratory.FIX activity rose to a plateau of 50-65 IU/dL and stayed there.None of the 65 determinations fell below 5%, and 89% exceeded 40%.The annualised bleeding rate fell from 1.66 to 0, and factor use was limited to 2,000 IU on day +1.The HEAD-US score did not change.There were four ALT elevations.The first two, on day +34 and during the taper, required full-dose prednisone (PDN): corticosteroid treatment lasted 335 days, with about 7.4 g in total.The last two appeared off corticosteroids, 11 days after withdrawal and in month 15.The third resolved with observation alone.The fourth was treated with PDN 15 mg/day for seven days, after which ALT fell to 50 IU/L and FIX rose to 64.8 IU/dL, and the PDN dose was then reduced to 10 mg/day.That episode has since resolved, with ALT 26 IU/L and FIX 58.3 IU/dL at the most recent determination, on day +491.No second-line immunosuppression was given.At 15 months after a single infusion, FIX expression remains in the non-haemophilic range and the patient is clinically well, with no bleeding and no factor use.The firstyear milestone of the payment agreement has been verified.The price was prolonged corticosteroid exposure, in a scenario for which we found no published guidance.