In this article you will learn:
- What eltrombopag is and which patients with aplastic anaemia can receive it
- How emicizumab works in haemophilia A and which people are eligible
- What the gene therapy products Roctavian and Hemgenix deliver and to which cells
- How a phase I trial of expanded regulatory T cells is designed and what it measured
- What you are asked to report during a trial and to whom
- What your rights are when a trial stops or you stop participating
- Where you can search for a trial that is open to participants
What are aplastic anaemia and haemophilia?
Aplastic anaemia (AA) is an autoimmune bone marrow failure disorder in which the immune system attacks blood-forming stem cells in the bone marrow, causing dangerously low blood counts[1]. Because the marrow stops producing adequate numbers of red cells, white cells and platelets, patients may present with anaemia, susceptibility to infection and bleeding. The condition can be severe or very severe depending on how far the blood counts have fallen[2].
Haemophilia A is an inherited bleeding disorder caused by a lack of factor VIII[3]. Haemophilia B is an inherited bleeding disorder caused by the lack of factor IX, a protein needed to produce blood clots to stop bleeding[4].
Haemophilia A is an X-linked, recessive disorder caused by mutations within the factor VIII gene. The clinical presentation ranges from mild to severe and correlates with the patient's residual plasma factor VIII activity level[5]. The same logic of residual clotting factor activity underlies the classification of haemophilia B, in which the missing protein is factor IX rather than factor VIII[4].
How is severe aplastic anaemia treated today?
Allogeneic stem cell transplantation from an HLA-matched sibling donor is a preferred first-line treatment option for younger patients with severe or very severe aplastic anaemia, while immunosuppressive treatment is an alternative option for others[2].
The standard immunosuppressive regimen combines horse anti-thymocyte globulin with cyclosporin A. In most countries horse anti-thymocyte globulin has become unavailable and has been replaced with rabbit anti-thymocyte globulin. Later comparative studies showed that outcomes with rabbit anti-thymocyte globulin plus cyclosporin A were similar or inferior to horse anti-thymocyte globulin plus cyclosporin A[2].
Standard treatment with strong immunosuppressive drugs is associated with considerable side effects, and up to a third of patients do not respond to them. Patients who do respond may relapse and require long-term immunosuppressive medication[1]. About half of patients treated with immunosuppression do not achieve a haematological response, or relapse afterwards[2]. Eltrombopag is authorised for adults whose disease is not controlled by immunosuppressive therapy and who cannot receive a stem cell transplant[6].
What is eltrombopag and which patients can receive it?
Revolade is an authorised medicine in the European Union. Its active substance is eltrombopag. It is used in adults with acquired severe aplastic anaemia. Their disease is not controlled by immunosuppressive therapy. They also cannot receive haematopoietic stem cell transplantation. In this procedure, the patient's bone marrow is replaced by stem cells from a donor[6].
The medicine is available as tablets and as a powder to prepare an oral suspension, can only be obtained with a prescription, and treatment should be started and supervised by a doctor experienced in treating blood diseases. The dose depends on the patient's age and the disease being treated and is adjusted as needed to maintain the appropriate platelet level[6].
How does eltrombopag work?
A hormone called thrombopoietin stimulates platelet production by attaching to certain receptors in the bone marrow. Eltrombopag attaches to and stimulates the same thrombopoietin receptors, which increases platelet production and improves platelet counts. This mechanism explains why the medicine is useful in a marrow-failure setting in which platelet output is inadequate, and why the dose is titrated against the platelet count achieved[6].
What did the clinical studies show?
In adults with primary immune thrombocytopenia, two main studies compared eltrombopag with placebo. These studies involved a total of 311 previously treated patients. In the first study, 59% of patients taking eltrombopag (43 out of 73) reached a platelet count of at least 50,000 per microlitre after 6 weeks. This compared with 16% of those taking placebo (6 out of 37). In the second study, the 135 patients taking eltrombopag were around 8 times more likely to reach the target platelet count than the 62 patients given placebo. The target platelet count was between 50,000 and 400,000 per microlitre during the 6 months of treatment[6].
In children aged 1 to 17 years with immune thrombocytopenia, one main study of 92 previously treated children lasted 13 weeks. Around 40% of those taking eltrombopag (25 out of 63) had a platelet count of at least 50,000 per microlitre for at least 6 out of 8 weeks between week 5 and week 12 without rescue medication. This compared with around 3% (1 out of 29) of those taking placebo[6].
How is haemophilia A treated with emicizumab?
Hemlibra is an authorised medicine in the European Union whose active substance is emicizumab, used to prevent or reduce bleeding in patients with haemophilia A. This includes patients who have developed factor VIII inhibitors – antibodies that act against factor VIII medicines – and patients without inhibitors if their haemophilia A is severe or moderate with a severe bleeding phenotype[3].
Emicizumab is a monoclonal antibody designed to do the work that factor VIII normally does, bringing together two clotting factors, IXa and X, as part of the chain of reactions needed for blood to clot. Because emicizumab has a different structure from factor VIII, it is not affected by factor VIII inhibitors[3].
How is emicizumab given at home?
The medicine is available as a solution for injection under the skin in the belly, thigh or upper arm. Patients or their carers may inject it at home once they have been trained appropriately, and the arm injection should only be given by a caregiver or healthcare professional[3].
The dose depends on bodyweight: 3 mg per kg once every week for the first 4 weeks. After that, the dose is either 1.5 mg/kg once every week, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. The medicine is intended for long-term use. The day before starting treatment, patients should stop treatment with bypassing agents such as activated prothrombin complex concentrate or recombinant factor VIIa[3].
What did the clinical studies show?
A study in 109 patients showed that patients with haemophilia A of any severity who had factor VIII inhibitors and were given emicizumab for prevention had fewer bleeds needing treatment – equivalent to 3 per year. Patients who received no preventive treatment had the equivalent of 23 per year. When patients already taking preventive bypassing agents were switched to emicizumab, treated bleeds fell from the equivalent of around 16 per year before the switch to around 3 per year afterwards. Quality of life scores were better than in those not given emicizumab[3].
A study in 152 patients assessed severe haemophilia A without factor VIII inhibitors. Patients given emicizumab for prevention had around 1 treated bleed per year. Patients who received no preventive treatment had 38 bleeds per year[3].
What gene therapies have been authorised for haemophilia?
Roctavian is an authorised medicine in the European Union for treating severe haemophilia A in adults who do not have inhibitors against factor VIII and no antibodies against adeno-associated virus serotype 5 (AAV5). Its active substance is valoctocogene roxaparvovec, and it is a gene therapy product, a medicine that works by delivering genes into the body[7].
Haemophilia A is rare, and Roctavian was designated an orphan medicine on 21 March 2016. It is given as a single infusion into a vein over a number of hours, the dose depends on bodyweight, and it should be given in a facility equipped to promptly treat infusion-related reactions[7].
Hemgenix is an authorised medicine in the European Union for treating adults with severe and moderately severe haemophilia B who have not developed inhibitors against factor IX. Its active substance is etranacogene dezaparvovec, and it is also a gene therapy product. Haemophilia B is rare, and Hemgenix was designated an orphan medicine on 21 March 2018[4].
Hemgenix is given once as a single infusion into a vein lasting one to two hours. Before the infusion the patient has tests including tests of liver health and for factor IX inhibitors, and patients are monitored closely for at least 3 months afterwards to decide whether additional factor IX replacement therapy is needed[4].
How do the gene therapies work?
Roctavian is made of a modified AAV5 virus containing the gene for factor VIII. After administration the virus is expected to carry the gene into liver cells so that they produce the missing factor VIII for a long period, and this type of virus does not cause disease in humans[7].
Hemgenix is based on a virus containing copies of the gene responsible for producing factor IX. The virus carries the gene to liver cells, enabling them to produce the missing factor IX and thereby limit bleeding episodes, and this type of virus does not cause disease in humans[4].
What did the gene therapy studies show?
| Product | Population studied | Key result reported by EMA |
|---|---|---|
| Roctavian (valoctocogene roxaparvovec) | 134 adult male patients with severe haemophilia A[7] | 104 weeks after a single dose, 75.4% had average factor VIII activity of at least 5 IU/dL; yearly bleeding episodes fell by 85.5% and the need for factor VIII replacement dropped by 97.5%[7] |
| Hemgenix (etranacogene dezaparvovec) | 54 adult male patients with severe or moderately severe haemophilia B[4] | Yearly bleeding rate fell from 4.2 to 1.5 bleeds per year; 96% of patients (52 out of 54) no longer needed factor IX replacement therapy for up to 2 years after the infusion[4] |
Roctavian received a conditional authorisation, which means the Agency decided its benefits are greater than its risks but the company will have to provide additional evidence after authorisation[7]. For Hemgenix there are uncertainties about how long the benefits last, because the main study evaluated the response in a small number of patients for up to 2 years[4].
The most common side effects of Roctavian, which may affect more than 3 in 10 people, are increased liver enzyme levels (alanine aminotransferase and aspartate aminotransferase), increased lactate dehydrogenase, nausea and headache[7]. The most common side effects of Hemgenix, which may affect more than 1 in 10 people, are headache, increased levels of certain liver enzymes and flu-like symptoms[4].
What other approaches are being tested in clinical trials?
A phase I trial led by Professor Ghulam Mufti provided the first evidence that autologous regulatory T-cell therapy is feasible and safe in people with aplastic anaemia and may have clinical benefit. Patients with aplastic anaemia have reduced numbers and impaired function of regulatory T cells (Tregs), immune cells that normally suppress harmful autoimmune responses and maintain immune tolerance[1].
Six people with severe or treatment-resistant aplastic anaemia were recruited to the trial. Some of their blood was removed and filtered to separate white blood cells with Tregs, and billions of Tregs were produced for each patient in a Good Manufacturing Practice (GMP) laboratory[1].
Two infusions were administered two weeks apart, and the study met its primary goal of confirming that the treatment was safe, with no serious treatment-related adverse events. Three patients experienced meaningful clinical benefit and remain independent of red cell or platelet transfusions. The infused Tregs peaked around day 28 and were still present in the bone marrow 6 months after treatment[1].
Preclinical research on stem cell gene therapy for haemophilia A focuses on safe and efficient transfer of nucleic acids into haematopoietic stem cells. It also focuses on optimisation of the factor VIII transgene for high expression. Another focus is reducing the toxicity of the conditioning regimen used for stem cell engraftment. Research also aims to overcome complications due to pre-existing factor VIII immunity[5].
Haemophilia A has been a candidate for gene transfer-based therapies. Even modest increases in factor VIII levels – 1% of normal levels or more – can alleviate spontaneous bleeding episodes. Many cell types can synthesise functional factor VIII protein[5].
What does taking part in a trial involve for you?
Trials of these treatments differ in what they ask of participants. Some compare an active medicine with placebo over weeks. Others follow patients for two years or more after a single infusion. Some monitor blood counts and transfusions[6].
- Visit schedule and tests – before a gene therapy infusion you have tests that include liver health and a check for inhibitors; after the infusion you are monitored closely for at least 3 months to decide whether you need additional factor replacement[4].
- Blood sampling – in the Treg trial, blood was removed and filtered to separate white blood cells, and two infusions were given two weeks apart[1].
- Stopping a previous medicine – the day before starting emicizumab, patients stop treatment with bypassing agents[3].
- Long-term follow-up – the effect of a gene therapy is assessed over years, and in the Roctavian study the increase in factor VIII activity was sustained for at least 2 years[7].
What must you report during a trial, and to whom?
Report any new symptom, bleeding episode, hospital stay or change in your medicines to the trial team, using the contact details in your participant information[3].
Some effects are expected and are tracked systematically: in the gene therapy studies these included increases in liver enzymes, nausea, headache and flu-like symptoms[7]. In the emicizumab studies, anti-emicizumab antibodies leading to loss of efficacy were uncommonly observed, which is why a return of bleeding is important to report[3].
Reports from trials and from routine use are collected in EudraVigilance, the European database for suspected adverse reactions, and in the national system of your country[6].
What rights do you have as a trial participant?
You can ask what will be measured, how long you will be followed and what happens to your samples, and you can withdraw from a trial at any time[1].
Ask specifically about long-term follow-up, because the duration of benefit from a gene therapy is uncertain and the main Hemgenix study followed a small number of patients for up to 2 years[4]. Ask also whether the treatment you receive is authorised, conditionally authorised or still experimental: Roctavian, for example, was authorised on the basis of less comprehensive data than normally required, with additional evidence to be provided after authorisation[7].
Where can you search for a trial?
Ask your haematologist whether any trial is open for your diagnosis. For gene therapies, eligibility depends on factors such as inhibitor status and the presence of antibodies against the viral vector used[7].
When should you contact your care team?
If bleeding returns or increases after starting a preventive treatment, this should be discussed with your haematology team, because loss of efficacy has been observed with emicizumab[3].
Seek urgent assessment if you develop signs of a liver problem after a gene therapy infusion – the most common side effects of Roctavian and Hemgenix include increased liver enzyme levels[7][4].
In aplastic anaemia, report fever, new infections, bruising or worsening fatigue to your treating doctor, who will check your blood counts[2].
Summary
Eltrombopag, emicizumab, Roctavian and Hemgenix each act on a defined molecular target, and their trial results are reported with the number of participants, the duration of follow-up and the size of the effect. Eltrombopag stimulates thrombopoietin receptors to raise platelet production, emicizumab bridges factors IXa and X to substitute for factor VIII, and the two gene therapies deliver factor VIII or factor IX genes to liver cells[6][3][7][4]. Ask your team which of these is authorised for your diagnosis, on what evidence, and whether follow-up beyond the study period is planned for you[7].
If you are considering a trial, read the participant information for the visit schedule, the tests before and after treatment, and the contact route for reporting symptoms.
❓ Which patients with aplastic anaemia can receive eltrombopag?
Revolade (eltrombopag) is authorised in the European Union for adults with acquired severe aplastic anaemia whose disease is not controlled by immunosuppressive therapy and who cannot receive haematopoietic stem cell transplantation. It is available as tablets and as a powder for oral suspension, only with a prescription, and treatment must be started and supervised by a doctor experienced in treating blood diseases. The dose depends on age and disease and is adjusted to maintain the appropriate platelet level.
❓ How does emicizumab reduce bleeding in haemophilia A?
Emicizumab is a monoclonal antibody designed to do the work of factor VIII by bringing together clotting factors IXa and X in the chain of reactions needed for clotting. Because its structure differs from factor VIII, it is not affected by factor VIII inhibitors. It is injected under the skin at home after training, with dosing based on bodyweight – 3 mg/kg weekly for 4 weeks, then a choice of 1.5 mg/kg weekly, 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks.
❓ Is gene therapy for haemophilia a one-time treatment?
Roctavian and Hemgenix are each given as a single intravenous infusion. In the Roctavian study, the increase in factor VIII activity was sustained for at least 2 years, and 75.4% of 134 patients had average factor VIII activity of at least 5 IU/dL at 104 weeks. In the Hemgenix study, 96% of 54 patients (52 out of 54) no longer needed factor IX replacement for up to 2 years. How long the benefit lasts beyond that period remains uncertain.
❓ Who is not eligible for the haemophilia gene therapies?
Roctavian is for adults with severe haemophilia A who have no inhibitors against factor VIII and no antibodies against adeno-associated virus serotype 5 (AAV5). It must not be given to people allergic to its ingredients, with an active or chronic infection not controlled by medicines, or with significant liver fibrosis or cirrhosis. Hemgenix is for adults with severe or moderately severe haemophilia B without factor IX inhibitors, and must not be given in the same liver and infection situations.
❓ What happens during the phase I trial of regulatory T cells in aplastic anaemia?
Six people with severe or treatment-resistant aplastic anaemia had blood removed and filtered to separate white blood cells containing regulatory T cells (Tregs). Billions of Tregs were grown for each patient in a GMP laboratory and given back as two infusions two weeks apart. The study met its primary safety goal with no serious treatment-related adverse events; three patients had meaningful clinical benefit and remained independent of red cell or platelet transfusions, and infused Tregs were still present in the bone marrow at 6 months.
❓ What should I report during treatment or a trial?
Report any new symptom, bleeding episode, hospital stay or change in your medicines to your trial team or treating doctor using the contact details in your participant information. Bleeding that returns or worsens matters especially with emicizumab, because anti-emicizumab antibodies leading to loss of efficacy have been uncommonly observed. After a gene therapy infusion, report signs of liver problems, since increased liver enzymes are among the most common side effects of both Roctavian and Hemgenix.
❓ Where can I find a trial that is open to me?
Trials in the European Union are listed in the Clinical Trials Information System (CTIS) at euclinicaltrials.eu, and worldwide in ClinicalTrials.gov and the WHO ICTRP. Trials recruiting in Europe can also be searched on clinicaltrials.eu. Take the trial reference to your haematologist, who can check eligibility against your age, disease severity, inhibitor status and, for gene therapy, antibody status against the viral vector.
- [1] King's College London – New treatment shows promise for patients with rare blood disorder (accessed 10 June 2026) — https://www.kcl.ac.uk/news/new-treatment-shows-promise-for-patients-with-rare-blood-disorder
- [2] Recent advances in treatment of aplastic anemia - PMC — PubMed Central (accessed 20.10.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC4219959/
- [3] European Medicines Agency (EMA) – Hemlibra (accessed 10 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/hemlibra
- [4] European Medicines Agency (EMA) – Hemgenix (accessed 10 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/hemgenix
- [5] Engineered Hematopoietic Stem Cells as Therapeutics for Hemophilia A - PMC — PubMed Central (accessed 20.10.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC4220243/
- [6] European Medicines Agency (EMA) – Revolade (accessed 10 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/revolade
- [7] European Medicines Agency (EMA) – Roctavian (accessed 10 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/roctavian
