10/12/2024
India’s First in human Gene Therapy for Hemophilia A supported by Department of Biotechnology : India’s first in Human Gene Therapy with lentiviral vector for Severe Hemophilia A in a single center study resulted in an annualised zero bleeding rate in all the 5 subjects enrolled with the production of Factor VIII for a prolonged period of time thus obviating the need for repeated infusions. This scientific accomplishment supported by the Department of Biotechnology and developed by Centre for Stem Cell research (CSCR) at CMC, Vellore, a translational unit of BRIC-inStem heralds a new era of transformational therapies in low resource settings for previously incurable diseases.
Haemophilia is a serious bleeding disorder caused by the deficiency of clotting factors, (i.e., Factor VIII and Factor IX proteins), leads to spontaneous bleeding episodes, and a reduced quality of life for patients and their families. Even though Hemophilia is a rare disorder, India has the World’s second largest burden of Hemophilia with a case load of 1.36,000. Severe Hemophilia A is managed with repeated factor VIII replacement or hemostatic products that stop or prevent bleeding. Prohibitive cost, venous access especially in children, patient acceptance etc are some of the bottlenecks with respect to standard of care Hemophilia therapy.
Gene therapy using viral vectors which introduces a normal copy of the gene has emerged as a paradigm-changing therapeutic option for Hemophilia. In the case of haemophilia, gene therapy provides the body with the ability to produce Factor VIII, so that the need for repeated infusions can be obviated. Scientists from CSCR have undertaken development of an alternate system for restoring Factor VIII expression, using a lentiviral vector in place of AAV vector. Based on promising preclinical data a first-in-human clinical trial was conducted to evaluate the safety and feasibility of this gene therapy technology for severe hemophilia A involving five participants who received autologous haematopoietic stem cells (HSCs) transduced with lentiviral vector expressing Factor-VIII gene. These HSCs give rise to blood cells producing functional factor-VIII protein for a substantial time period, thereby, obviating need for repeated infusions.
The participants were followed up for 6 months after undergoing therapy. Factor VIII activity was observed to correlate with vector copy number in the peripheral blood. The annualized bleeding rate was observed to be zero for all five participants over a cumulative follow-up of 81 months. The study was published in the New England Journal of Medicine (DOI: 10.1056/NEJMoa2410597).
