Haemophilia is a bleeding disorder that affects millions of people worldwide. According to the Haemophilia and Health Collective of North (HHCN), India has the second-largest population of haemophilia cases in the world, with an estimated 1,36,000 cases affected by haemophilia A. Besides this, India is the first country to classify haemophilia patients as disabled under the Rights of Persons with Disability Act in 2016.
Haemophilia is an inherited bleeding disorder that is diagnosed at birth. It is a condition where you’re born with the absence of one clotting factor in your blood, which is required for a blood clot. So, when a person gets wounded or suffers an injury, they will keep on bleeding until a particular blood factor is injected.
Haemophilia A and Haemophilia B, caused due to deficiency or dysfunction of a protein called Factor VIII (FVIII) and Factor IX (FIX) respectively, which is probably caused due to genetic mutations. Clotting involve coagulation cascade. It involves as many as 20 different special proteins called coagulation, or clotting, factors. Factor VIII (eight) is one such coagulation factor.
Both Haemophilia A and B are inherited and X-linked disorders (a mutation in a gene on the X chromosome). Females have two copies of the X chromosome. So if the factor VIII gene on one chromosome does not work, the gene on the other chromosome can do the job of making enough factor VIII. Males have only one X chromosome. If the factor VIII gene is missing on a boy’s X chromosome, he will have hemophilia A. For this reason, most people with hemophilia A are male. It is often first seen when an infant is circumcised. Other bleeding problems usually show up when the infant starts crawling and walking. Mild cases may go unnoticed until later in life. Symptoms may first occur after surgery or injury. Internal bleeding may occur anywhere.
Although there is no cure for hemophilia A, current treatments are very effective. Treatment consists of replacing the missing clotting protein (factor VIII) and preventing the complications associated with the disorder. The U.S. Food and Drug Administration (FDA) has approved several recombinant forms of factor VIII for the treatment of hemophilia A including Helixate FS, Recombinate, Kogenate FS, Advate, ReFacto, Eloctate, Nuwiq, Adynovate, Kovaltry, Jivi, and Xyntha.
In some cases, people with hemophilia A may develop “inhibitors” against the replacement factor VIII which are specialized proteinsthat may recognize replacement factor VIII as “foreign” and create antibodies, which target and destroy the replacement factor. But gene therapy can circumvent this problem because it supplies the original form of protein encoded by gene definitely or/and indefinitely.
Earlier, in November 2022, Hemgenix, a gene therapy that treats hemophilia B in adults was approved by FDA which was first gene therapy for hemophilia, and the first to use an adeno-associated virus (AAV) vector. In 2023, a one time gene therapy called Roctavian was also approved by the FDA to treat adults with severe hemophilia A, which contains a viral vector carrying a normal F8 gene.
In India, ImmunoACT, supported by IIT-B and Laurus Labs, got approval from CDSCO for NexCAR19, India’s first CAR-T cell therapy for the treatment of r/r B-cell lymphomas and leukemia.
In the recent gene therapy advancement, five participants 22 to 41 years of age with severe hemophilia A without factor VIII inhibitors were transduced with CD68-LV-ET3 — a lentiviral vector including a new F8 transgene (ET3) with a myeloid-directed CD68 promoter. The results from this clinical study validate a new approach to gene therapy for severe hemophilia A through transplantation, after myeloablative conditioning, of autologous HSCs transduced with a lentiviral vector. No unexpected safety issues were encountered. After receiving gene therapy, all participants had clinically significant circulating factor VIII activity levels that were sufficient to completely abrogate spontaneous bleeding and that remained stable after the first 3 to 6 months during a follow-up period ranging from 9 to 27 months.
The study was supported by grants from the Department of Biotechnology, Ministry of Science and Technology, Government of India, the National Institutes of Health and a grant from Hemophilia of Georgia.
