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Ethical Considerations in Gene Therapy for Sickle Cell Disease and Thalassemia (with Prof Mariane de Montalembert) · EHA Unplugged

• 0:03
  Greetings and welcome to EHA Unplug, the official podcast
• 0:06
  channel of the European Hematology Association EHA.
• 0:10
  Hello, I am Isabel Olivera, a medical writer for EHA.
• 0:14
  Welcome to our podcast exploring the ethical considerations
• 0:18
  surrounding the distribution and access to gene therapy for
• 0:22
  sickle cell disease and thalassemia.
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  Today we have the privilege to have with us Professor Marian de
• 0:30
  Montalamberc, A renowned expert in pediatric hematology and
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  medical ethics. Professor de Montalamberc has an
• 0:39
  extensive experience in treating blood disorders and has been at
• 0:44
  the forefront of discussions on the ethical implications of this
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  Co teenage therapies. Thank you for being with us
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  today. Thank you for inviting me.
• 0:55
  So we want to talk about sickle cell disease and thalassemia
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  first. What is the standard of care at
• 1:06
  the moment for sickle cell disease?
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  In Europe In Europe, the standard of care is first to
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  have a neonatal screening. Neonatal screening is absolutely
• 1:19
  mandatory because it allows to start very early the prevention
• 1:26
  of the complication of sickle cell disease.
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  Basically, the treatment relies on antibiotherapy to prevent
• 1:35
  primococcal diseases. Today in primococcal diseases
• 1:40
  are the first cause for death and it in children and it is
• 1:45
  very important to be able to prevent those primococcal
• 1:49
  infections and we can do that with ammunisation and daily
• 1:54
  penicillin. And then the second standard of
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  Care now is for children with HPSS and has been a 0
• 2:03
  thalassemia to use hydroxyurea very soon.
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  These both these treatments are affordable to patients in
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  Europe. They are not affordable in many
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  countries in for instance in sub-Saharan Africa and as well
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  as there is almost rarely A systematic neonatal screening in
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  sub-Saharan Africa. With these measures, the more
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  than 97% of children reach adulthood.
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  So if these treatments are not available in South Saharan
• 2:45
  Africa, what is the standard of care there?
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  There I should say that there is almost no standard of care in
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  Africa given that they cannot afford both of the treatments
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  and which explain which explains the very high mortality of rate
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  in children in sub-Saharan Africa.
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  Iniquity in the access to care is one of the most important
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  ethical problem raised by sickle cell disease.
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  So there has been a lot of research in new drugs also for
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  sickle cell disease and thalassemia.
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  Which drugs are available at the moment in Europe?
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  The best example is hydroxyurea, because it is really in the
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  standard of care in Europe for HBSS and HBS BT0 thalassemic
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  children, which represents the vast majority of the patients.
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  And it is started as early as nine months of age.
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  And it is not available in most African countries.
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  And also a safe transfusion is a very important difference in
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  Europe, because in Europe we have a safe blood and in Africa
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  very often there is not enough blood and not enough control for
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  safety, for infectious and immunological issues.
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  So there is really a very different access to care in
• 4:22
  Europe and in the the United States and in Africa.
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  So most of these drugs that we are very excited about now in
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  Europe like luspatercept I think and mitapivat and all of these
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  and of course gene therapy because of their price tag also
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  will never be available widely. So, but I'm surprised about
• 4:52
  this, that you're talking about drugs that are not expensive,
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  like hydroxyurea is not expensive, at least by European
• 5:00
  standards, and even that is not available yet in these
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  countries. What are your thoughts on how to
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  ameliorate this situation so that a better treatment can be
• 5:15
  accessed in these countries? Hydroxyurea it is not costly at
• 5:19
  all for European the more than for European children.
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  All the of the institutions give it for free to the patients.
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  But in Africa it's even if it is not expensive in our European
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  meaning it is expensive for African parents, they have to
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  pay for the drug and they count. I had a colleague and he said I
• 5:46
  give Hydroxura every four months because it's too expensive to
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  give it every day. So every four months I, I think
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  that there is a baseline level for the patient, but it means
• 5:58
  that three months over 4, the child is not treated, but it's
• 6:02
  for cost problems. So in fact, children, they
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  survive and they have most of them, they have a good life.
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  The median duration of hospitalisation for children in
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  my hospital, it is one week per year.
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  It's perhaps too much, but it is one week, one week per year.
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  But then they enter into adolescence and adulthood and
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  they face new and really very heavy complications.
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  But so far there are very, very few available drugs today
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  because the drugs you have quoted, for instance, Etavo
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  Pivot, Meta Pivot, they are in research and they are not
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  available today. And for instance Chrysolismab,
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  which and tell a lot of hope, but it is available in United
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  States but no more in Europe. And voxelotor has been stopped.
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  So in fact there are not many drugs besides hydroxyurea.
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  And the other point is that patients that know that cure is
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  possible. And when you propose a drug to a
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  family, she says I want a cure, How to offer the cure?
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  There are first option. It is bind marrow
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  transplantation. Bind marrow transplantation cues
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  95% of children who have an HLA identical sibling.
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  But you need to have an HLA identical sibling.
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  And less than 20% of children everywhere have an HLA identical
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  sibling. So once you have an HLA
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  identical sibling, you have 95% probability of being cured.
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  In Africa, there is no HLA typing and there is very few
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  possibility to perform a bone marrow transplantation.
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  Please note that. Since this conversation was
• 8:01
  recorded, reports of successful bone marrow transplantations in
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  Tanzania and other African countries were presented first
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  at the Global Congress on Sickle Cell Disease in Abuja in June
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  2025 and then at the annual Sickle Cell and Thalassemia
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  Conference hosted by Ascot in October 2025.
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  After the vast majority, 80% of patients, they do not have an
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  insular identical sibling. So there is a huge hope
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  represented by gene therapy. The first experience in gene
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  therapy was published 10 years ago.
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  It was one of my patient. He was a boy, 13 years old from
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  the Caribbean island and he was submitted to mostly transfusion
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  and he was cured and it was fantastic.
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  He was cured 10 years ago. But after time has passed around
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  a lot of experiments with several techniques either using
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  Dean addition which was a technique used for this patient.
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  But not all the patients given Dean addition were cured,
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  majority of them but not all of them.
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  And also there is gene editing. These techniques they may be
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  very efficient but it they are awfully expensive and we do not
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  have long term results. For instance, in the gene
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  addition techniques, there were two reports of leukemias after
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  and which led the regulatory agencies to be very careful and
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  to add a lot of follow up data. And they say, yes, lot of
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  promises, but we need more time to be sure that there are no
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  side effects. And there is a question of
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  communication because it's very difficult for patients.
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  They read this patient has been cured, Why not my son?
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  Of course, but the communication needs to be done very honestly.
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  And telling the parents, it's not so much a matter of money.
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  It is because in fact, sickle cell disease by itself is
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  awfully costly. When you consider mostly
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  transfusional or when you consider repeated
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  hospitalization, it is very costly.
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  What is really a problem is that the institution and the
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  agencies, they ask for more follow up.
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  They they say there are two cases of leukemia.
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  Why, how, how to be sure that the therapy will be totally well
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  safe. And they ask for time and very
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  often the communication for the, for the, the patients, they,
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  they do not understand it. They say it's a problem of
• 11:00
  money, but not only it's a problem of money.
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  And sometimes also they're not informed.
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  You know, I, I, I, I see patients every week and some
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  patients they say, oh, no, doctor, you are asking me
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  immunisation accounts influencing I don't want it is
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  risky. I won't ban marriage transplant,
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  but they are not informed or they say, no, I don't want bone
• 11:23
  marrow transplant, I want gene therapy.
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  But it is the same chemotherapy which raises the question of
• 11:29
  preservation of fertility, because it has to be performed,
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  because these chemotherapy have to be combined with preservation
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  of fertility and there is a huge problem of communicating to
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  patients what is really the treatment.
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  I was in a meeting called ASCAT 2 months ago and I made a
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  presentation on gene therapy and people, they were totally
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  unhappy because they understood that there was a chemotherapy,
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  there was a need for preservation of fertility.
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  And also finally, when the damages of the disease are too
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  severe, there is no hope to reversion of what has been
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  already damaged. So there is a very, I should say
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  not narrow but not very wide window to offer those cures
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  because after the damages are irreversible.
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  So everything, everyone thinks it's a matter of money.
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  It is a problem, but also it's there, there are a lot of
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  problems. There are you need to have a
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  very advanced to have a very good hospitalized, a very good
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  hospital yard. I had to make a one month ago a
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  presentation for Africa. So first you need to have a
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  minimum of settings to be able to perform gene therapy in
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  Europe. There is another issue when I
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  decide that one of my children I'm following needs a bone
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  marrow transplant. I'd say it is a common decision
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  with the band marrow unit with the family with and then the
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  decision is taken and then the child has to wait for around one
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  year. Why?
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  Because there is no room, because there are no nurses.
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  Because now the reality in most hematological yard is that there
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  are lack of nurses. So he has to wait to find a
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  room. And if we open and add the
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  question of gene therapy, we are not going to stop by
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  nurtransplant. So we need to recruit nurses.
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  So it is all system which has to be modified so that cure can be
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  a reality. But today money is not the only
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  question. Of course, 2,000,000 per patient
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  is a question but all the system has to be organized differently.
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  So inequity between North and South is huge, but it is not
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  only about gene therapy, it is about the need to have blood in
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  the South. It is about the need to have
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  morphine, it is about the need to have free care because they
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  pay for blood, they pay for morphine, they pay for
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  antibiotics in the South and they have no money.
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  There are problems in Europe because also in Europe resources
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  are limited, but there are also problems of informing patients
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  or really choosing which is the patient that can get this
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  therapy, but we are ages away of what the problems are in Africa
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  or in. You're right.
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  So how do you think there's any way that we can help improve
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  this? Inequity or.
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  In the treatment of sickle cell disease.
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  I think that awareness has to be increased in the South
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  countries. Some health authorities consider
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  that sickle cell disease should be considered for instance as
• 15:27
  well how HIV was considered because for HIV money came from
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  the North and as I think that for sickle it should be the
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  same, the north should give money so that government should
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  not pay for sickle cell disease. This is a political problem.
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  I am not able to answer how to solve this problem that it
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  should be considered by governments as a priority for a
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  country and it is not so far. So this is the first problem and
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  if it was considered as a priority, governments could make
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  care standard of carefree or avail affordable, which is not.
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  This is the first step to make of course, hydroxyribic
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  penicillin. People are dying from meningitis
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  in Africa and you can avoid it. First point, second point, bad
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  marrow transplant should be there should be short way to
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  aiming children coming from Africa to have a bad marrow
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  transplant. In Europe it has been done.
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  There are calibration, for instance, between I think
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  Tanzania and Italy, our dip sum, I think perhaps also in Nigeria.
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  The first point that there is no HLA typing in Africa.
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  It's not possible. I receive every week a letter
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  from a an African country. My daughter has a severe sickle
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  cell disease. I have four other children.
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  They have the same blood group, meaning that they do not know
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  that it is not a problem of blood group but of HLA typing.
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  So what I need is to have blood samples from the family coming
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  from Africa and to have a first control in Europe.
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  It's not easy. I I think that having a lab
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  performing each other, typing in some countries in Africa should
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  be the first step and it is feasible, but it has to be paid.
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  Then we can organise short shorter way to perform vimal
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  transplant in Europe. Second step, to have really
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  senses performing bone marrow transplants in Africa.
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  But it is a whole organization, the need to have safe blood, to
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  have not sterile but very clean yards and all, all of the
• 18:15
  organization which is needed. And I do not think that it will
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  be possible to perform gene therapy in countries who are not
• 18:23
  able to perform a bone marrow transplant.
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  It is a question but it you I think that given the severity of
• 18:32
  neutropenia or all the problems which are the same for all post
• 18:37
  chemotherapy protocols. You need to have some expertise
• 18:41
  in bimal transplant before experiencing genesis therapy.
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  It for me, it is a very, very late future in South Country
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  gene therapy who honestly, which is dramatic, but but in in
• 18:55
  Europe we can do better. But because if we are only on a
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  very pragmatical point. I think that 2 million of EUR if
• 19:05
  you can make life of people possible, reduce the burden of
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  the disease. It has to be.
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  I think that perhaps it could be done, but after you have to
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  organise, as I said or organization of hematological
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  system and it is a problem of the cost of very, very expensive
• 19:30
  drugs and which is globally known on the ethical but
• 19:34
  political and financial and it is a.
• 19:39
  Whole how can an association like EHA help to at least gain
• 19:48
  awareness or advocate in the places where decisions are made
• 19:56
  to improve the situation so to reduce this inequity, do you
• 20:00
  think AHA can? Do something.
• 20:05
  I think yes, because in the missions of AHS there is
• 20:09
  information and as we are doing now and information, it is the
• 20:15
  first step and it is a very good information.
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  Honestly, I don't, I'm not, I'm very happy to be part of EHA and
• 20:24
  rather proud of doing this job. And I think that EHA is very
• 20:28
  good in teaching and information.
• 20:32
  I think that creating documents and post casts and so on, we
• 20:39
  are, we are good. I think that we could think
• 20:42
  about collaborations and generalizing collaboration.
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  I think that also information documents to be targeted not
• 20:59
  only in specialists, but for life specialists, colleagues
• 21:03
  would be very important. Yes, I think that there are a
• 21:06
  lot of things and after all these debates about institution
• 21:12
  and regulatory agencies and access to care, EHC brings
• 21:18
  together a lot of people from different origins and lot of
• 21:23
  different jobs. EHC creates links between
• 21:28
  national societies. In Europe.
• 21:34
  Not all countries perform bad marit transplantation for non
• 21:40
  for benign diseases. For some countries it's
• 21:43
  difficult. So as though these countries are
• 21:48
  European. So I think that information
• 21:51
  really can be performed with EHE and by EHE.
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  So yes, the first step is information at the right level
• 22:01
  for the right people. I imagine because you need some
• 22:05
  kind of information for a patient, there is also
• 22:07
  information for other healthcare providers and I guess also
• 22:13
  information for the people who are taking their decisions to
• 22:16
  understand the situation of the patients, of the hospitals, of
• 22:21
  the. So I think there is a lot of
• 22:23
  work in that sense to improve to at least move the ball forward,
• 22:30
  get get it rolling. I agree and EHA is trying to
• 22:34
  help in that. And the other thing is really
• 22:38
  who's going to put the money, you know, to, to get a place
• 22:43
  that can do the transplant in, in another country in it, But
• 22:49
  that seems really far away. No, we can have common decision,
• 22:54
  but it is not only medical, it is politics and we can be within
• 23:05
  the discussion. Maybe what?
• 23:09
  Hematologists can do at the moment is point point the
• 23:11
  problems, really highlight them and through EHA is 1
• 23:16
  possibility, but to really highlight what the problems are,
• 23:19
  what they're facing. Is there anything else you would
• 23:21
  like to say for the audience? I think we are opening a very
• 23:30
  difficult discussion and we are one piece of the puzzle, but
• 23:38
  politics are other piece and I I think we have discussed how much
• 23:48
  it is difficult to and how much it will take time to go further.
• 23:54
  But I hope that international and European institutions will
• 23:59
  help. Yes, thank you.
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  Very much for thank you for this conversation.
• 24:06
  It has been really enlightening. And yeah, thank you for being.
• 24:11
  With us today, thank you for. Invitation Thank you to all of
• 24:14
  you for listening and if you like this episode, share it with
• 24:19
  your friends and see you for the next episode.