Nine-year follow-up data indicate that adeno-associated virus (AAV) gene therapy for haemophilia B offers sustained clinical benefits alongside a favorable long-term safety profile. However, the enhancement of full viral capsids did not show a significant improvement in outcomes. These results were highlighted at the 2026 Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), where they were awarded the top poster distinction.
Haemophilia B is a rare inherited bleeding disorder caused by a deficiency in factor IX, leading to recurrent bleeding and dependence on lifelong prophylactic replacement therapy. Previous studies on the scAAV2/8-LP1-hFIXco gene therapy revealed stable expression of factor IX and no long-term toxicity for over a decade. Nevertheless, some patients receiving higher doses experienced transient elevations in liver enzymes. To mitigate concerns regarding the immunogenicity linked to high capsid loads, a modified vector preparation enriched for full AAV capsids was developed and scrutinized.
In a study involving four adults with severe haemophilia B, a single intravenous infusion of the enriched vector was administered between 2014 and 2017, with a median follow-up of 9.8 years. Throughout the study, 47 treatment-related adverse events occurred, all of which were mild. Transient grade one transaminitis was noted in three participants early post-infusion, but no serious adverse events, factor IX inhibitors, thrombosis, or ongoing liver abnormalities were recorded during the follow-up.
Factor IX activity levels were dose-dependent, showing median values of 2% in the lower-dose group and 13.4% in the higher-dose group. Although factor IX levels decreased in the higher-dose group over time, they stabilized within a clinically relevant range. Two participants completely halted their prophylactic factor replacement, while the other two resumed treatment.
Significant improvements were noted among all participants. The mean annualized bleeding rate dropped from 11.6 before treatment to 3.2 during follow-up, and the average annual factor concentrate use decreased from 2,589 IU/kg to 1,301 IU/kg. The most substantial and sustained benefits were observed in the two participants who discontinued prophylaxis, demonstrating considerable long-term reductions in both bleeding episodes and factor use.
Overall, the findings affirm the long-term safety of systemic gene therapy for haemophilia B. Nonetheless, the enrichment for full AAV capsids did not lead to a noticeable decrease in liver toxicity or improve the durability of factor IX expression compared to earlier vector preparations.
Reiss UM and colleagues presented these findings, titled “9-year outcomes of scAAV2/8-LP1-hFIXco enriched for full AAV capsids in adults with severe hemophilia B,” as part of Abstract PO041 at the EAHAD 2026 Annual Meeting held from February 3 to 6, 2026.
Original Source: https://www.emjreviews.com/hematology/news/eahad-2026-nine-year-outcomes-of-gene-therapy/
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Publish Date: 2026-02-06 20:32:00
