Gene therapy shows long-term success in hemophilia B patients

A gene transfer approach to treating the bleeding disorder hemophilia B remains safe and effective long-term, as scientists from St. Jude Children's Research Hospital and University College London today report thirteen years of follow-up data. Hemophilia B is a rare genetic disorder caused by insufficient levels of a circulating protein called factor IX, which promotes blood clotting. The researchers used a one-time gene therapy intervention to address the disorder. Published in the New England Journal of Medicine, the 13-year follow-up study is the longest reported for any gene therapy for hemophilia B. The results, including an almost tenfold reduction in annualized bleeding rate, support the long-term viability of gene therapy for the disease's treatment. 

Hemophilia B is an X-linked genetic disorder affecting one in approximately 25,000 male births. While the disorder can range in severity, frequent spontaneous bleeding and life-threatening hemorrhages occur due to insufficient blood-clotting factor IX. Treatment for hemophilia B has traditionally been expensive for lifelong supplementation of the clotting factor, but gene therapy offers a potentially transformative means to address the disorder. 

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."

Andrew Davidoff, MD, St. Jude Department of Surgery chair, co-investigator on the study

Safety, efficacy and long-term viability 

The study included 10 adults with severe hemophilia B who received the gene therapy drug between March 2010 and November 2012, with initial safety and efficacy successes reported in 2014 in The New England Journal of Medicine. Now, over a decade later, the new 13-year follow-up report furthers these findings. The patients were followed over 10 additional years and have all maintained a steady level of factor IX and an excellent benefit in terms of freedom from bleeding. 

In the field of gene therapy, questions remain regarding the enduring viability of these treatments, with key stakeholders, including patients and families, waiting to see what the long-term outcomes will be, such as durability and stability of expression. "For these 10 patients, the factor levels are stable and have been at the same level across these 13 years," said principal investigator Ulrike Reiss, MD, St. Jude Department of Hematology. "Further, we have not seen any side effects or toxic events in the long-term follow-up." 

The lack of toxic events is noteworthy. Upon administering the gene therapy, over 90% ends up in the liver. The researchers kept a careful eye on this to ensure no issues arose, and while a small degree of liver inflammation was noted shortly after vector administration, it was curbed by steroid administration and did not return after initially resolving. 

The results point to a significant quality-of-life improvement for the treated individuals. Their annualized bleeding rate (how much someone bleeds over the course of a year) decreased from 14.0 episodes to 1.5 episodes. Additionally, even though patients did not get within the normal range of factor IX expression, their case was still significantly improved with less dependency on factor IX supplements. 

"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," said the study's chief investigator, Amit Nathwani, PhD, from UCL Cancer Institute and the Royal Free Hospital. "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."