EAHAD 2026: Nine-year outcomes of gene therapy

Nine year follow-up data shows that adeno-associated virus gene therapy for haemophilia B provides sustained clinical benefit with a favourable long-term safety profile, although enrichment for full viral capsids did not clearly improve outcomes. These findings were presented at the 2026 EAHAD Congress and were recognised as the top poster of the meeting.

Haemophilia B is a rare inherited bleeding disorder characterised by deficiency of factor IX, leading to recurrent bleeding and reliance on lifelong prophylactic replacement therapy. Earlier studies of scAAV2/8-LP1-hFIXco gene therapy demonstrated stable factor IX expression and no long-term toxicity for more than a decade, but transient liver enzyme elevations were observed in some patients receiving higher doses. To address concerns that high capsid load may contribute to immunogenicity, a modified vector preparation enriched for full adeno-associated virus capsids was developed
and evaluated.

Four adults with severe haemophilia B received a single intravenous infusion of the enriched vector between 2014–2017 and were followed for a median of 9.8 years. Across the cohort, 47 treatment-related adverse events were reported, all mild, with transient grade one transaminitis occurring early after infusion in three participants. No vector-related serious adverse events, factor IX inhibitors, thrombosis, or persistent liver abnormalities were observed during long-term follow-up.

Steady-state factor IX activity levels were dose dependent, with median values of 2 per cent in the lower-dose group and 13.4 per cent in the higher-dose group. Although factor IX levels declined over time in the higher-dose participants, expression stabilised within a clinically meaningful range. Two participants discontinued prophylactic factor replacement entirely, while two resumed prophylaxis.

Clinically relevant improvements were observed across all participants. Mean annualised bleeding rate fell from 11.6 before treatment to 3.2 during follow-up, alongside a reduction in mean annual factor concentrate use from 2,589IU/kg to 1,301IU/kg. The greatest and most sustained benefit was seen in the two participants who remained off prophylaxis, with marked long-term reductions in bleeding episodes, and factor consumption.

Overall, these findings support the long-term safety of systemic gene therapy for haemophilia B. However, enrichment for full adeno-associated virus capsids did not clearly reduce liver toxicity or enhance durability of factor IX expression compared with earlier vector preparations.

References

Bradbury H. EAHAD 2026: Nine-year outcomes of gene therapy. European Medical Journal. Feb 6 2026. Available at: www.emjreviews.com/hematology/news/eahad-2026-nine-year-outcomes-of-gene-therapy/

Reiss UM et al. Nine-year outcomes of scAAV2/8-LP1-hFIXco enriched for full AAV capsids in adults with severe haemophilia B. Abstract PO041. EAHAD 2026 Annual Meeting, 3–6 February 2026