New Lentiviral Vector–Transduced Hematopoietic Cell Therapy Shows Favorable Effect in Hemophilia A

In a study of gene therapy for severe hemophilia A, patients received autologous CD34-positive hematopoietic stem cells (HSCs) transduced with the CD68-ET3-LV lentiviral vector.

The study was conducted by a team of investigators from Christian Medical College Vellore in Vellore, India; Emory University School of Medicine in Atlanta, Georgia; and Expression Therapeutics in Tucker, Georgia. They published their findings in The New England Journal of Medicine.

“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,” the investigators reported.

The single-center study enrolled five participants aged 22 to 41 years who had severe hemophilia A without factor VIII inhibitors. They underwent myeloablative conditioning and then received autologous CD34-positive HSCs transduced with CD68-ET3-LV at doses of 5.0×10⁶ to 6.1×10⁶ per kilogram of body weight. Three patients received the HSCs with a transduction enhancer, and two received HSCs without a transduction enhancer.

For all five patients over a cumulative follow-up of 81 months and median follow-up of 14 months, the annualized bleeding rate was zero. Severe neutropenia had a duration of seven to 11 days, and severe thrombocytopenia, a duration of one to seven days.

The three patients who received HSCs with transduction enhancer had vector copy numbers in their final drug product of 1.5, 0.6, and 2.2 copies per cell. Their median factor VIII activity levels after day 28 until their last follow-up visit were 37.1 IU/dL, 19.3 IU/dL, and 39.9 IU/dL, respectively. They had peripheral blood vector copy numbers of 4.4, 3.2, and 4.8 copies per cell, respectively.

The two patients who received HSCs without transduction enhancer had vector copy numbers in their final drug product of 1.0 and 0.6 copies per cell. Their median factor VIII activity levels after day 28 until their last follow-up visit were 5.2 IU/dL and 1.7 IU/dL, respectively. They had peripheral blood vector copy numbers of 0.2 and 0.1 copies per cell, respectively.

The Ministry of Science and Technology of the Government of India was among the funders of this study.

Reference

Srivastava A, Abraham A, Aboobacker F, et al. Lentiviral gene therapy with CD34+ hematopoietic cells for hemophilia A. N Engl J Med. 2025;392(5):450-457. doi:10.1056/NEJMoa2410597