Indian scientists develop novel gene therapy treatment for haemophilia

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Scientists in India have reported success with using gene therapy to treat severe haemophilia A, a rare hereditary condition resulting from a faulty gene which triggers severe, spontaneous, and potentially fatal bleeding episodes.

Though only tested on five patients in Tamil Nadu so far, none of them have reported bleeding episodes over an average follow-up period of 14 months. It is not unusual for those afflicted by haemophilia to have weekly bleeding episodes, requiring frequent treatment. The results of the study were reported in the peer-reviewed New England Journal of Medicine (NEJM) earlier this week.

The trial was led by Alok Srivastava of the Centre for Stem Cell Research (CSCR) at Christian Medical College, Vellore, and financially supported by the Union Department of Biotechnology.

One-time solution

The typical treatment for the condition requires injections at frequent intervals, with infusions of a ‘clotting factor’ to prevent bleeding. Gene therapy treatments, however, promise to be a one-time solution. A gene introduced into the body teaches it to create enough of the clotting factor that can prevent such haemorrhage.

Haemophilia can be classified as minor or severe depending on the percentage of clotting factor present in those afflicted. Haemophilia A, the more common version of the condition, is caused by the absence of a blood-clotting factor called Factor VIII. Even though haemophilia is a rare disorder, India has the world’s second largest patient pool, with an estimated 40,000 to 100,000 patients.

Those with Severe Hemophilia A have less than 1% of the clotting factor, and manage the condition with repeated Factor VIII replacement, monoclonal antibodies, or injecting substances that mimic Factor VIII to stop or prevent bleeding. Because of the nature of the condition and the relatively low numbers of patients, treatment can be expensive. A March 2024 research study in the journal Heliyon estimates the per patient cost of treating a haemophiliac in India to be $300,000 (or ₹2.54 crore) over a 10-year period.

Safer, more effective treatment

There is only one gene therapy — Roctavian — which was approved by the U.S. Food and Drug Administration for commercial use in 2023. Its effectiveness was established based on results from a cohort of 112 patients followed up for at least 3 years after Roctavian treatment. Following the infusion, the average bleeding incidents decreased from 5.4 bleeds per year at baseline to 2.6 bleeds per year. The majority of patients who received Roctavian also received corticosteroids to suppress their immune systems for the gene therapy to be effective and safe, according to the U.S. FDA.

Roctavian works by transporting the therapeutic gene into the body by using an adenovirus as a carrier or vector and involves the liver in producing Factor VIII. In the CMC trial, stem cells from the patients were fused with the clotting factor gene using another kind of vector, called a lentivirus.

‘Ground-breaking’

This approach, the authors say in their paper, is safer than using an adenovirus, and potentially opens up the gene therapy treatment to children.

An independent expert described the study as “ground-breaking.”

“This ground-breaking study is notable for several reasons. First, it establishes that initiating and executing studies involving new gene therapy is possible even in resource-constrained settings such as India,” said Johny Mahlangu, in an editorial in the NEJM. “[There is] the potential to localise the manufacture of gene therapy in India, resulting in reduced cost and increased gene therapy access beyond India. This breakthrough could remove other barriers, such as liver health and maturity, and the need for immunosuppressive therapy,” Dr. Mahlangu added.