A single injection replaces long-term therapy. The first patient benefits from completely new prospects thanks to the new method.
Able to play sports again: Marvin M. wearing the jersey and baseball cap of his favourite American football team. Copyright: Karin Kaiser/MHH
Going on holiday, playing sport and feeling healthy – things that most people take for granted were just a dream for Marvin M. for a long time. The young man suffered from severe haemophilia B, a form of bleeding disorder that severely restricted his life. The turning point came with a new type of treatment at the Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation at Hannover Medical School (MHH). Marvin M. received gene therapy and now has a good chance of long-term good health. He is the first patient in Germany to be treated with this type of therapy for haemophilia B.
Hereditary coagulation disorder
Haemophilia B is a hereditary blood clotting disorder caused by a deficiency of coagulation factor IX. The symptoms are the same as those of haemophilia A. ‘The blood plasma of those affected coagulates more slowly. There is a risk of bleeding into large joints and muscles, sometimes even into the gastrointestinal tract or the central nervous system, even with the slightest injury or spontaneously,’ explains Professor Andreas Tiede from the Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation. The bleeding has serious consequences. For example, it can completely destroy joints in the long term. Both men and women are affected by this hereditary disease. However, almost exclusively men suffer from a severe form of the disease. Professor Tiede estimates the total number of severe haemophilia B patients in Germany to be around 500. In these patients, the activity of coagulation factor IX is less than two percent of the norm. To increase clotting activity, they must inject themselves with the missing factor IX for the rest of their lives. Since it has a short half-life, this is usually twice a week.
The disease was stressful
Marvin M. knows all too well about regular injections. He also had to inject himself twice a week at first, but later only once a week after changing medications. However, despite the treatment, the disease remained a major challenge. It dominated his life and imposed limitations. No rough play, no sports, no school trips – all to avoid injury. And constant health problems. ‘As an infant, I had a brain haemorrhage that was repaired with surgery,’ reports the now 33-year-old. In addition to frequent severe nosebleeds, his right ankle also caused him concern. It had bled several times during his childhood and had to be operated on in 2017. ‘However, surgical procedures were generally difficult. Because haemophilia B is a very rare disease, many doctors are unsure and it often took a long time before anything was done,’ says Marvin M., recalling a dental operation and a surgical procedure after an accident at work on his hand. ‘It all weighed heavily on me.’
Gene therapy offered good prospects
Fortunately, however, his paediatrician was very knowledgeable about haemophilia. ‘She continued to care for me into adulthood and made me aware of the possibility of gene therapy,’ reports Marvin M. So in 2023, he came to the MHH to see Professor Tiede. ‘Thanks to weekly prophylactic injections, the patient had a coagulation activity of about 5 percent of the norm at the end of the week. That's not bad. But gene therapy offered him the prospect of perhaps reaching 15, 20 or even 30 percent, and that in a stable long-term manner without fluctuations within a week,’ explains the expert.
No quick decision
However, there is no guarantee of success with gene therapy for haemophilia B. That is why the decision was not made quickly. ‘There is simply a lot to consider and weigh up,’ says Professor Tiede, summarising the months-long joint process with Marvin M. This involves the advantages and disadvantages of the therapy and a comparison with other treatment options, individual risks, personal expectations and preferences. And finally, the patient's willingness to accept restrictions during therapy and to anticipate possible side effects and their consequences. ‘The patient must be given balanced and open-ended advice in order to ultimately make the best decision for themselves,’ says Professor Tiede. Marvin M. was determined to undergo the therapy because he saw great opportunities for himself and his future in it.
Healthy gene supplements the patient's gene
On 30 June this year, the time had come. The young man received a single injection of the gene therapy drug, which has been approved in Europe since 2023. The gene therapy is based on the adeno-associated virus (AAV). The virus is modified in the laboratory beforehand so that it can only enter the patient's cells once. It is not capable of reproduction and no longer contains any of its own genes, only the gene for factor IX. ‘This gene remains in the cell nucleus next to the chromosomes as a tiny ring. The patient's factor IX gene remains as it is. The healthy gene is only added,’ explains Professor Tiede. It is therefore a complementary gene therapy. The healthy gene then produces coagulation factor IX. Two weeks after gene therapy, Marvin M. was able to stop his previous injection treatment. The coagulation activity of factor IX was 30 percent and remains stable to this day. There was only a minor dip in the short term because an immune reaction occurred and liver values rose. ‘However, we were able to manage this side effect with short-term cortisone therapy,’ explains Prof. Tiede. If that had not worked, haematologist Professor Dr Heiner Wedemeyer could have been consulted. The director of the Clinic for Gastroenterology, Hepatology, Infectiology and Endocrinology is considered a specialist in liver health in gene therapies and is involved in the care of patients.
‘Quality of life ten times better’
Both Professor Tiede and Marvin M. are very happy with the results of the gene therapy. ‘Not having to take injections anymore means a tenfold improvement in my quality of life,’ says the young man enthusiastically. Thanks to the good and stable activity of coagulation factor IX, he no longer has to struggle with bleeding. This means he can finally play sports such as football, basketball and, above all, American football. ‘This sport is very close to my heart. Now I can not only cheer on my favourite team, I can also try out the sport myself. That means a lot to me.’ Marvin M. can also finally go on holiday abroad. ‘I have so many plans that my girlfriend has to slow me down,’ he says with a wink. Professor Tiede is also optimistic. ‘We will of course remain vigilant, but there is real hope that Mr M. will remain in this stable condition for many years to come,’ he says. The haematologist considers gene therapy to be particularly suitable for haemophilia because its effects can be easily measured at any time via blood samples. "Nevertheless, it remains one of many treatment methods for haemophilia. It is not suitable for every patient. But for some, it works very well."
Text: Tina Götting