Hematology · 17 h ago
Two Patients Develop Persistent FVIII Inhibitors After ASC618 Gene Therapy
A report in Blood describes two patients with hemophilia A who developed high-titer factor VIII inhibitors after receiving ASC618 in a phase 1/2 trial. Both remain on emicizumab prophylaxis, with inhibitor titers still high nearly two years after infusion.
- Two recipients developed high-titer factor VIII inhibitors.
- Inhibitors persisted nearly two years after infusion.
- Both patients are maintained on emicizumab prophylaxis.
- The phase 1/2 trial has been halted.
ASC618 is an AAV-based gene therapy for hemophilia A that uses ET3, a bioengineered human-porcine chimeric factor VIII transgene. In the phase 1/2 trial NCT04676048, two patients received a single infusion. Both initially expressed factor VIII but subsequently developed high-titer factor VIII inhibitors.
The inhibitor titers have declined but remain high nearly two years after treatment. Both patients are maintained on emicizumab prophylaxis. The trial has been halted, according to the report.
The authors suggest that the ET3 transgene contained epitopes to which the patients had not developed tolerance, despite each having more than 1,000 prior exposure days to exogenous factor VIII. These two cases highlight a potential immunogenicity concern for bioengineered factor VIII transgenes, including in previously treated patients. The report concerns only two patients, and the proposed explanation is not established by the information available in the abstract.
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Blood: Cases of High-Titer Inhibitor Formation After AAV Gene Therapy for Hemophilia A ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.