Recent advances in hemophilia gene therapy

Available treatment options for people with hemophilia (PWH) have rapidly advanced in recent years. As we approach World Hemophilia Day on the 17^th of April, we shine a light on the most recent advent in hemophilia treatment.

Traditional treatment vs Gene therapy

Caused by deficiencies in clotting factors, hemophilia has traditionally been treated by on-demand or regular (prophylactic) injections to help the blood clot properly and reduce the risk of excessive bleeding. However frequent injections can be burdensome for PWH and their families¹.

In June of last year, the European Medicines Agency (EMA) approved the first gene therapy to treat hemophilia A, Roctavian™² followed by the approval of Hemgenix^® in November to treat hemophilia B³. These groundbreaking therapies are administered as a one-time treatment and aim to provide a solution that should last for years, rather than weeks^2,3. This could be life changing for PWH and their families and significantly reduce burden in terms of time and ongoing prevention of bleeding.

Transformational impacts of gene therapy

Recent clinical trial data showed that treatment remained effective two years after trialling Roctavian™ and Hemgenix^®2,3. During this time, researchers have explored the short-term impact of gene therapy on PWH. Participants from a UK-based interview study stated that the most important impact of gene therapy was on their quality of life and no longer requiring weekly injections⁴. Participants noted that this had a transformational influence on their work and social lives, eliminating the need for frequent travel and the ability to recover from minor injuries without injections⁴.

There are however factors related to gene therapy that have been found to have a negative impact on PWH, such as the use of immunosuppressants, used to prevent inflammation after gene therapy. One study found that PWH felt unprepared for the side effects of immunosuppression, and unsupported when it came to managing them¹. Research involving the use of immunosuppressants after organ transplants has shown that adherence levels can be surprisingly low, resulting in rejection of the new organ and additional health risks⁵. To support adherence to treatment and improve patient experiences, educational and support programs should be provided for PWH and healthcare professionals involved in their treatment.

The future of gene therapy

Gene therapy can have a positive impact on mobility and pain and provide freedom from invasive weekly treatments. While we look to the future of gene therapy, it is important to remember that the patient journey throughout each stage of treatment is individual and the PWH and their families may require additional support before and during the therapy process. This support should include strategies such as early and ongoing education, adequate provision of psychosocial support and tools to manage adherence to immunosuppressants and other treatment requirements¹. Recognising challenges at each stage from the PWHs viewpoint is vital to ensure that each person can achieve the greatest benefit from gene therapy⁶.

References

1. Fletcher, S., Jenner, K., Pembroke, L. et al. The experiences of people with haemophilia and their families of gene therapy in a clinical trial setting: regaining control, the Exigency study. Orphanet J Rare Dis 17, 155 (2022). https://doi.org/10.1186/s13023-022-02256-2

2. European Medicine’s Agency (2022, June 24). First gene therapy to treat severe haemophilia. https://www.ema.europa.eu/en/news/first-gene-therapy-treat-severe-haemophilia[Accessed 2nd April 2023].

3. US Food & Drug Administration (2022, November 22). FDA Approves First Gene Therapy to Treat Adults with Hemophilia B. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b [Accessed 2nd April 2023].

4. Aradom E, Gomez K. The patient gene therapy journey: findings from qualitative interviews with trial participants at one UK Haemophilia centre. J Haemophilia Pract. 2021. https://doi.org/10.17225/jhp00174.

5. Gandolfini, I., Palmisano, A., Fiaccadori, E., Cravedi, P., & Maggiore, U. (2022). Detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation. Clinical kidney journal, 15(7), 1253–1274. https://doi.org/10.1093/ckj/sfac017

6. Noone,D.,Astermark,J.,O’Mahony,B.,Peyvandi,F.,Khair,K.,Pembroke,L. & Jenner,K.(2022).The journey of gene therapy in haemophilia – putting the patient at the centre of the hub and spoke model. The Journal of Haemophilia Practice,9(1) 156-166. https://doi.org/10.2478/jhp-2022-0021