BHUBANESWAR: In a significant medical breakthrough, India’s first human gene therapy with a lentiviral vector for severe haemophilia-A has been found to be successful with zero bleeding rate in patients. Haemophilia is a serious bleeding disorder caused by blood deficiency of clotting factors (factor VIII and factor IX proteins). It can lead to spontaneous bleeding episodes, joint damage, and a reduced quality of life for patients and their families.
The new gene therapy has shown promising results during the first phase trial on five patients, aged between 22 and 41. The annualised bleeding rate has been observed to be zero in all five patients over a cumulative follow-up of 81 months. Supported by the Department of Biotechnology, this first-in-human gene therapy for haemophilia-A patients, has been developed by Centre for Stem Cell Research (CSCR) at CMC, Vellore.
Results of the study conducted on the patients have been published in the recent edition of New England Journal of Medicine. Dr Alok Srivastava, lead author of the study and head of haematology research unit at St John’s Research Institute, Bengaluru, said excellent outcomes were observed in median factor-VIII levels, which were assessed during the treatment, and follow-up for a period of around two years.
“No spontaneous bleeding events occurred in any of the patients during or after the gene therapy. Before the therapy, all patients had reported an annualised bleeding rate of at least 20 events. The results of this clinical study reveal a new opportunity for gene therapy that can be offered to all haemophilia-A patients, possibly at an early age,” Dr Srivastava said. Haemophilia is a rare disorder and India has the world’s second largest burden with a case load of 1.36 lakh.
Hemophilia-A is the most common form and accounts for about 80-85% of cases. The availability of factor VIII replacement therapy, the cornerstone of hemophilia treatment, is limited and expensive. Dr Rabindra Kumar Jena, bone marrow transplant physician at SCB Medical College and Hospital, Cuttack, said, haemophilia is a bleeding disorder that slows the blood clotting process.
Haemophilia-A is the most common type of the condition affecting one in every 5,000 births, he said. Physicians believe that the new gene therapy developed by CMC Vellore would be a game changer in haematology treatment across the globe. What’s gene therapy Unlike conventional treatments that require regular administration of clotting factor concentrates, gene therapy offers a one-time or infrequent intervention. This therapy can enable the body to produce factor VIII autonomously, potentially providing a lifelong solution.
As part of the therapy, stem cells are extracted from the blood of the patient, and after certain gene corrections, the cells are transplanted back with a lentiviral vector. The therapy provided the body with the ability to produce factor VIII, ensuring that there is no need for repeated infusions. “The therapy is a new innovation and proved very effective during the first phase trial. It can drastically reduce the frequency and severity of spontaneous bleeding episodes, by restoring clotting factor VIII levels.
This would improve patients’ overall quality of life. The therapy, being developed indigenously, could be more affordable and accessible,” said Dr Jena. With successful gene therapy, patients may no longer need to rely on clotting factor concentrates or plasma products, which are often scarce or expensive. “It could also pave the way for more advanced genetic treatments for other rare diseases,” Dr Rajeeb Swain, senior scientist at Institute of Life Sciences (ILS), Bhubaneswar, said.
