The study, published in New England Journal of Medicine , is the longest reported follow-up for any gene therapy for haemophilia B, a rare genetic disorder caused by insufficient levels of a protein in the blood, called factor IX (nine), that promotes clotting after injury.
The study included 10 adults with severe haemophilia B who received the gene therapy drug (called scAAV2/8-LP1-hFIXco) between March 2010 and November 2012, with initial safety and effectiveness results reported in 2014.
But questions remained about whether the therapy would continue to be safe and effective over time, with key stakeholders, including the patients and their families, waiting to see what the long-term outcomes would be.
Now, over a decade later, the new study confirms that the patients maintained a steady level of factor IX in the blood, with a median reduction from 14 bleeding episodes to 1.5 bleeding episodes per year. This represents an almost tenfold reduction in their annualised bleeding rate (how much someone bleeds over the course of a year).
This is important as fewer bleeds means less pain, fewer hospital visits, and a lower risk of long-term joint damage, significantly improving the patients’ quality of life. It also means less need for clotting factor infusions, which are the usual treatment for haemophilia B.
Professor Amit Nathwani, chief investigator of the study from UCL Cancer Institute and the Royal Free Hospital, said: "It’s incredibly rewarding to see the sustained safety and efficacy, which truly validates the potential of gene therapy as a one-time treatment for this condition. Our findings answer critical questions about the long-term durability of gene therapy, offering profound hope and a significantly improved quality of life for patients."
Haemophilia B is a genetic disorder affecting approximately one in 25,000 men, caused by mutations in the F9 gene responsible for producing the factor IX protein. While the disorder can range in severity, frequent spontaneous bleeding and life-threatening haemorrhages can occur without sufficient factor IX in the blood.
Treatment for haemophilia B has traditionally been through expensive lifelong injections of the clotting factor, but gene therapy offers a potentially transformative means to address the disorder. The therapy is delivered to the patient’s cells using an adeno-associated virus (AAV) that had been genetically engineered to carry a functioning copy of the F9 gene.
Andrew Davidoff, MD, co-investigator on the study from St. Jude Department of Surgery, said: "The key benefit is that gene therapy is a one-time, simple intravenous infusion that’s very straightforward to do, and potentially has positive effects for a lifetime."
The treatment, marketed under the name Hemgenix, was approved by the UK’s National Institute for Health and Care Excellence (NICE) in 2024, making it available as a treatment option for some adults with moderately severe or severe haemophilia B. Jude.
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Matt Midgley
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