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TOPLINE:

Lentiviral vector (LV)–based gene therapy using CD34+ hematopoietic stem cells (HSCs) demonstrated stable factor VIII expression in severe hemophilia A patients, with higher vector copy numbers correlating to increased factor VIII activity. All five participants maintained zero bleeding events throughout the follow-up period, suggesting potential long-term efficacy.

METHODOLOGY:

• Researchers conducted a single-center study involving five participants aged 22-41 years with severe hemophilia A without factor VIII inhibitors.
• Participants received CD68-ET3-LV–transduced autologous CD34+ HSCs at doses of 5.0×10⁶ to 6.1×10⁶ per kg after myeloablative conditioning.
• Treatment assessment focused on safety endpoints including engraftment and regimen-related toxic effects, and efficacy endpoints including factor VIII activity and annualized bleeding rate.
• Follow-up duration extended to September 30, 2024, with a median follow-up of 14 months (range, 9-27).

TAKEAWAY:

• Vector copy numbers in the final drug product ranged from 0.6 to 1.0 copies per cell for group 1 and 0.6 to 2.2 copies per cell for group 2 participants.
• Median factor VIII activity levels after day 28 were 1.7-5.2 IU per deciliter in group 1 and 19.3-39.9 IU per deciliter in group 2, correlating with peripheral-blood vector copy numbers.
• The annualized bleeding rate was zero for all five participants over a cumulative follow-up of 81 months.
• Participants demonstrated successful engraftment with median time to neutrophil engraftment of 11 days and platelet engraftment of 15 days.

IN PRACTICE:

“Gene therapy for hemophilia A with the use of lentiviral vector-transduced autologous HSCs resulted in stable factor VIII expression, with factor VIII activity correlating to vector copy number in the peripheral blood,” wrote the authors of the study.

SOURCE:

The study was led by Alok Srivastava, MD, Christian Medical College in Vellore, India. It was published online on December 9 in The New England Journal of Medicine. 

LIMITATIONS:

Given the small number of participants in this study, all statements are qualitative and based on inspection of data without statistical analysis. The study was conducted at a single center with a relatively short median follow-up of 14 months.

DISCLOSURES:

The study was supported by grants from the Department of Biotechnology, Ministry of Science and Technology, Government of India, and the National Institutes of Health. Additional funding was provided by Hemophilia of Georgia. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.