Gene therapy for haemophilia: hopes for a bleeding-free life
Haemophilia patients have relied on lifelong injections of the missing clotting factors. A single dose of a newly approved gen therapy could be sufficient.
In hereditary haemophilia, blood clotting is impaired and blood does not clot at all, or only clots very slowly. 17 April 2023 marks the World Haemophilia Day.
What you should know about the new gene therapy:
- It is based on a recombinant adeno-associated virus (AAV) that does not reproduce in humans. It contains the blueprint for the respective missing clotting factor.
- After injection, the genome is taken up by the liver cells, which then produce factor VIII or factor IX independently.
- Due to antibodies being formed against AAV, the therapy can only be carried out once.
Haemophilia: Rare but serious
Haemophilia is a hereditary coagulation disorder in which very few functional coagulation factors (FVIII in haemophilia A, FIX in haemophilia B) are produced. With a frequency of 1:10,000, it is one of the rare diseases. Due to the X-linked recessive inheritance, most of those affected are male.
Depending on the residual activity of the FVIII or FIX proteins present, a distinction is made between different degrees of severity. In severe haemophilia, the risk of spontaneous bleeding into joints, muscles, internal organs and brain is particularly high. 17 April 2023 is the World Haemophilia Day.
Significantly fewer haemophilia-related bleedings
As a monogenic disease, haemophilia is a candidate for gene therapy and has been the focus of research for some time. In addition, even a slight increase in clotting activity can significantly reduce the risk of bleeding. However, it is still questionable how long the effect will last.
In any case, the data from the approval studies are so far optimistic. In most of the 134 patients with haemophilia A from the phase 3 trial, an increased factor VIII level was still measurable two years after treatment, which was also clinically reflected: The bleeding rates decreased by 85%.
Similar results were seen in haemophilia B. In two prospective, open studies with 57 patients, the bleeding rates dropped from 4.19 to 1.51 bleeds per year and have now remained stable for over three years in the first subjects.
Keeping an eye on liver values
The treatment is generally well tolerated. Immediately after the treatment, flu-like symptoms, fever, nausea and muscle pain may occur, but these disappear after a few days.
An increase in liver values is relatively common, due to an autoimmune T-cell reaction. In order not to jeopardise the effectiveness of the treatment, the early use of corticosteroids is recommended. This normalises liver values and factor expression in most cases.
High therapy costs
Sustained increase of the factor concentration, significant reduction of the bleeding rate and increase of the quality of life - all this has its price. With therapy costs in the millions of euros for a single treatment, the new gene therapy drugs are among the most expensive medications worldwide. Approval is still only conditional. Further clinical data must show in the future whether the costly use of gene therapy for haemophilia really proves its worth.
Haemophilia therapy: Conclusion for medical practice
With the conditional approval by the EMA, Roctavian and Hemgenix have taken the first step towards market maturity. This means that, for the first time, drugs for the treatment of haemophilia are available that promise to be free of bleeding for a long time. For those affected, this means an enormous gain in quality of life. Further studies must show whether the effect actually lasts permanently.
1. Miesbach W, Klamroth R, Oldenburg J, Tiede A: Gene therapy for hemophilia – opportunities and risks. Dtsch Arztebl Int 2022; 119: 887–94. DOI: 10.3238/arztebl.m2022.0353
2. European Medicines Agency (EMA): First gene therapy to treat severe haemophilia A. News 24/06/2022. Online unter https://www.ema.europa.eu/en/news/first-gene-therapy-treat-severe-haemophilia (letzter Aufruf: April 2023).
3. European Medicines Agency (EMA): First gene therapy to treat haemophilia B. News 16/12/2022. Online unter https://www.ema.europa.eu/en/news/first-gene-therapy-treat-haemophilia-b (letzter Aufruf: April 2023).