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Patient Perspectives on Gene Therapy for Sickle Cell Disease and B-Thalassemia · EHA Unplugged

• 0:06
  Hello, I am Isabella Libera, a medical writer for the European
• 0:10
  Hematology Association EHA. I have the pleasure to have here
• 0:14
  with me today Miriam Santos Freire and Lourdes Brunetta.
• 0:19
  Welcome to both of you for and thank you for being with us
• 0:22
  today. Can you please introduce
• 0:24
  yourselves, please, Miriam first.
• 0:27
  Hello, so I am Miriam. I have sickle cell SSI, am
• 0:33
  Portuguese and British. I was born in Angola.
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  I lived in Portugal for about 40 years and for the past 10 years
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  I have been living in UK. Lately in Cambridge where I
• 0:44
  learned about patient advocacy and I have been developing my
• 0:48
  role with two heads. A white sickle cell patient
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  living in the UK outside of London or Birmingham where
• 0:55
  everything happens and the Portuguese patients
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  representative worldwide. Part of the boards of the
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  Portuguese Hemoglobinopathies Association, APPDH and
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  representing Portugal within the ERN, Eurobudnet, the European
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  Sickle Cell Federation, the European Hematology Association
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  Patient Advocacy Committee and the Red Cell Network in the Uki
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  am a full time language consultant, married with no
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  children. Thank you very much.
• 1:25
  Can you please introduce yourself, Laurice?
• 1:28
  Yeah, of course. Thank you.
• 1:29
  Thank you for this invitation. I'm Laurice Brunetta.
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  I I'm based in Italy, in Geneva in particular, and I'm patient
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  with thalassemia, with better thalassemia major.
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  I'm 61. So I have I, I went through all
• 1:50
  the story of the disease because when I was born, thalassemia was
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  a fatal disease still and my prognosis when I was born and
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  diagnosed when I was 3 1/2 years old was still the adolescence.
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  And now I'm 61 and many other, many other patients across in,
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  in maybe in the Western countries are older than me.
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  So this means that we can survive with this disease and,
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  and deal with this disease in a bad way.
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  I'm, I'm, I'm based in Italy. I'm a patient advocate since
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  more than 40 years now because my participated, I established a
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  local association here in Italy when we started to work for the
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  patient advocacy. But also I'm a founding member
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  of Palestinian International Federation back in 1986 and a
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  lot of other activities and as Miriam as well a patient in the,
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  in the patient advocacy committee of the HA in the, in
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  the governance of Europe net, the the Europeans reference
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  metrophoreomatological disorders and in many other also many
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  other organization for air diseases, in particular for
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  developing policies for rare diseases and also just for
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  educating the patients to claim for their rights.
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  So thank you very much to both of you for agreeing to be our
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  guest. Today we're going to be
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  discussing what are patients thinking about gene editing.
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  So you are both patients yourselves from sickle cell
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  disease and thalassemia, but you are also in contact with other
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  patients through this all, all your engagements in patient
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  advocacy groups. So my first question is really
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  basic is what is it like today to live with these two diseases?
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  What does it involve as everyday burden?
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  What do you have to do often? What is it like to live with
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  this? So can you please explain medium
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  first? So sickle cell is the is the how
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  can we say it? Well, it's a red blood cell
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  disorder, non malignant red blood cell disorder and
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  individuals affected by sickle cell carry the sickle hemoglobin
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  S gene mutation on at least one beta globin gene.
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  And this is important for the gene therapy because this is the
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  one that is the key to solve the mystery.
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  And normally healthy red blood cells are round and by conquer
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  in shape, they move around the body carrying oxygen.
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  But in sickle cell, the red blood cells resemble the shape
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  of a farming tool known as the sickle.
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  So like a sea, right? Well, it can be, it can have
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  various shapes, but usually we call it like that.
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  So it's not a, a round one. It has spikes and things.
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  And so with less oxygen, the blood becomes more.
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  Thick and they. Tend to clog, especially in the
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  joints, and that causes the the the.
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  The main thing is. Severe pain, but also acute
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  chest syndrome, organ damage and many other things reducing life
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  expectancy. So day-to-day usually is with
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  fatigue, a lot of fatigue because hemoglobin levels are
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  lower, much lower than than usual.
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  And then it's the pain is a is a day-to-day companion for it.
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  It varies depending on the patients.
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  It varies if it's chronic pain or if it is it, if it has to do
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  with the crisis. Usually adolescence and infancy
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  is more complicated in terms of hospital admission.
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  So it's really disabilitating. We miss school a lot.
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  We suffer a lot from differences in temperature, dehydration.
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  So that that's the day today. The, the, the, the, until now
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  there are no curative treatments.
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  The only one is the bloods, the bone marrow transplant, which is
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  only for a few, unfortunately, and it involves chemotherapy and
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  the gene therapy will be another one as well.
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  And unfortunately, for about 30 years we didn't have any new
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  drugs there. There is only hydroxuria, which
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  is not valid for everyone. Not everyone is eligible for it.
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  And many patients also go through regular blood
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  transfusions with a lot of risks because the veins are not good
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  and the complications with our insulation and a lot of
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  different things. But the two drugs that came out
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  recently, voxelotor and quiz and rizumab, after not a long time
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  in the markets, they were withdrawn because it wasn't
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  there was no evidence that the risk that the benefits would
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  outweigh the risks. And so that's the journey for
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  now, indicated 1. Thank you.
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  And what is your experience? Thalassemias because you know
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  it's not only one disease but it's a group of diseases has
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  different outcomes according to the severity of the genotype and
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  and the clinical phenotype of the disease.
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  So this means that the situation where so-called non transfusion
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  dependent thalassemia that can have a better outcomes, even
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  though they occasionally can have blood transfusion red blood
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  cell packed in blood transfusion, but in in low
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  amount during the year. People with thalassemia
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  intermediate. It is what we call today non
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  transfusion dependent thalassemia that and in in a
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  very close, very close to the threshold to the to the
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  thalassemia major and they're required to be transfused
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  regularly. And of course the thalassemia
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  major patient like me, we, we must have we we must be
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  transfused regularly every three weeks.
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  And so this meant in term of quality of life, because the
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  main issue is always for for us and for the people affected by
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  sickle cell is the quality of life.
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  We in in the Western world are very lucky because we had an
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  excellent good standard of care developed across the years and
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  also the possibility to access very easily to the standard of
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  care and also to the drugs that are on the market for targeting
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  the complication etcetera. But thinking about Thalassemia
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  and as a board member of the Thalassemia International
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  Federation, Thalassemia has published a review in 2023, and
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  they make an investigation across the world.
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  Among the patients with thalassemia, only less than 7
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  percent, 7% in the world can have access to the optimal care.
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  The other people are still struggling to survive with this
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  disease. The treatment consists in blood
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  transfusions regular for for the most most severe genotype, the
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  Palestinian major beta 0 beta zero in genotype means to be
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  refused regularly every two four weeks with 2-3 blood units of
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  red blood cell pact and to have a multidisciplinary care to be
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  to have to to have the availability of iron chelating
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  agents. Because accumulating the old the
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  the iron transfuse with the blood transfusions accumulating
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  the organs like the liver, the heart and provoke lot of damages
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  and malfunctioning of this organs.
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  So we need to be chelated from all this iron.
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  Also, multidisciplinary care means that we have we can we can
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  suffer occasionally from many other complication, primary and
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  secondary of thalassemia like osteoporosis, endocrine problems
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  and many other situations that should be monitored and tackled
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  timely in order to avoid the development of western
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  situations that can of course impact on the quality of life
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  and also on the lifespan. So to summarize what a patient
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  that needs transfusion at the moment, because not all of them
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  are transfusion dependent as you said, needs to be transfused.
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  A patient will need to be transfused every three weeks
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  more or less. This is a huge burden.
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  You will have excess iron accumulating, so you need
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  chelation. So this will be the normal
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  burden of severe patients, you know, severe thalassemia
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  patients and sickle cell disease too.
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  Many sickle cell, many cells also go through it.
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  The what I know is the cycles are usually it's slightly
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  different. Although there are.
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  Patients who? Accumulate sickle cell and
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  thalassemia. So the scenarios can change, but
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  many patients go through our transfusion dependence and they
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  go on every six weeks or every eight weeks.
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  It's not exactly the same because the disease is not the
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  same on every patient. And even in the same patient,
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  which is one of the difficulties.
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  Prices are not always the same. There are many different
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  factors. I, I, people always like a
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  little bit of numbers to, to put things into perspective, there
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  is a, a, a real effort to work on national registries to put
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  numbers and to know because currently it's the, it's, it's
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  considered the largest genetic disease, largest growing genetic
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  disease, sickle cell. It is said that worldwide 8
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  million people are estimated to have sickle cell disease.
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  It's an inherited disorder, right?
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  Most of those are in the United States.
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  Most of those in the United States and in the UK are of
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  black origin, so African and Caribbean.
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  But worldwide the reality is not exactly like that.
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  So it's predominantly a disease coming from Africa and
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  Caribbean, Yes, but there is also coming from Middle East,
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  the Mediterranean basin. It's mainly prevalent in low
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  income areas. And so that's exactly what Loris
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  was saying. So access to standard care is
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  difficult. Numbers are difficult to qualify
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  it and it's difficult to push for it and to advocate for it.
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  But we are on a on the right. Track and gene.
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  Therapy will be. The difference is that until now
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  we have we, we've been having treatments and medication to
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  address the symptoms and to improve the quality of life.
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  But with bone marrow transplant and gene therapies, we are
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  really talking about a potential cure, and that will be key,
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  yeah. This is what I was going to ask
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  you now because Kasgebis has has done a lot of noise obviously is
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  the 1st CRISPR based gene therapy that has been approved
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  worldwide is the first case of a CRISPR based gene therapy.
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  And so this really has the potential to cure the disease.
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  Of course, because it's the first treatment, there are
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  doubts about it also, and this is what we wanted to ask
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  patients, how is this landing in the patient space?
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  What are your thoughts about receiving gene therapy?
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  Because potentially there is a cure, but obviously there are
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  always drawbacks possible, possible safety issues.
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  And this is that life therapy. So once it's been given once and
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  you have been treated with this gene therapy, you cannot go
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  back. So how are patients thinking
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  about this? We have the expectations to be
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  cured and not to have to deal anyway no longer with the
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  hospital with needles, with blood transfusions and medicine,
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  etcetera, etcetera. Of course, it's to to, to become
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  at this point, it's has been a very long run for scientists and
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  also for the patients. We know that in the process
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  there are challenges for the patients and the patients should
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  be aware of these challenges and should have the possibility to
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  discuss because it's not no, sometimes we are hearing about
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  speculation for finding the best candidate for this treatment.
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  This cannot be an algorithm to decide who is the best
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  candidate, who is the best candidate.
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  Only the patients can decide because because this should be
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  provided on a voluntary basis. Patients can ask, I have too
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  much of the burden of Palestinian.
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  I want to try the the the way of this new treatment, knowing the
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  rest for the future. We don't know.
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  We have to wait, I think quite a lot, before being aware of all
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  the complexities of these these situations.
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  I I think that the gene therapy as it is right now, it still
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  goes through chemotherapy the same way as a bone marrow
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  transplant does. And I think that the intention
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  with gene therapy as it evolves is to go to use the patient's
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  own stem cells and deviate from all the secondary infects and
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  the limitations of going through chemotherapy.
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  So that's also another thing that's let's hope that the
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  future of gene therapy will carry as well.
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  But it's the different scenarios between thalassemia and sickle
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  cell. For sickle cell, we're still
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  waiting. OK.
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  And just to give you numbers and there is quite a list of what
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  patients consider about not just gene therapy, but also gene
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  therapy. I was reading yesterday that for
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  example, patients going on hydroxyurea, the cost would be
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  approximately, I don't know, $1000 per year, right.
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  Patients going through voxelotor prison lizumab, it was estimated
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  to go through I think it was 100,000.
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  And the the the cost associated to the gene therapy is something
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  between 1.2 million and four point something which is
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  absolutely absurd and which puts it into in a scale what?
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  Loris was saying is very true about it, they must want it and
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  it is a long, long road going through either bone marrow or
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  gene therapy. I was reading a couple of cases
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  yesterday. It's about one year with long
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  hospital admissions. It's a it's a, a really long
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  thing. So I have no.
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  Idea and it's. It's really worthwhile knowing
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  what it entails. We are waiting for the
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  negotiation at national level for having access to gene
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  therapy. It's fundamental for every
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  patient's community to have the possibility to access gene.
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  This gene therapy, as I told before, it's should be a mutual
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  decision to discuss among the scientists, the the treating
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  physician, the patients, the families, because I think this
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  is main for the children rather than for adults.
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  Despite the of course, because treating a children children you
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  can justify the cost because you can cure the disease at the very
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  beginning. There are adults in severe
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  condition, really severe condition that need to be
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  treated as well. So the most important thing is
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  to have the possibility to access to this treatment and
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  then it's a choice. I think it's important to speak
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  about the need for both the disease, in this case, blood
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  requirements. The aim of gene therapy is
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  improving. It is improving the hemoglobin
• 20:51
  level sickle cell disease. It's not only improving the
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  hemoglobin level because there are many other implications,
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  particularly in adult patients because they have the, you know,
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  all the consequences of many years with the disease.
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  It's important to improve the standard of care.
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  My my major concern and, and and it's safe for thalassemia.
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  If I have an infection in the liver, I, I gene therapy with
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  for thalassemia cannot, cannot treat.
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  Also the infection I have in the liver, I have patients in with
• 21:30
  with thalassemia that underwent the liver transplants due to the
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  infections. So for this reason I thought
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  it's important for children, mainly that for adults.
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  And just just one thing about that is that what has been
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  approved is for patients over 12 or from 12 years onwards with a
• 21:53
  history of severe pain crisis, which are not eligible so for
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  other types of treatments. So you need you need to be,
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  there is a quotation from someone in the West, you have to
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  be sick, but not too sick. And it's exactly what Loris is
• 22:12
  saying. So you need to have a severe
• 22:17
  overall condition, but they need they take into consideration how
• 22:23
  far you are with the organ damage and everything.
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  If you can both give us a take away message from your
• 22:34
  perspective and the patient organizations you are involved
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  in, what would be a take away message from for the perspective
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  of this gene therapy for the patients that are listening?
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  My take on message is very simple.
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  I think of course as told before this gene therapy is this
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  innovative treatments, this potentially curative, one time
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  curative is it's excellent, excellent for the patients that
• 23:06
  lives for a long time with such a disease impacting disease on
• 23:12
  the quality of life. So the message is very easy.
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  Of course, we need to push this way in order to find better
• 23:20
  solution for the challenges we have to face.
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  We need for the patients to have a good standard of care, safe
• 23:28
  blood for blood transfusion, accessibility to iron chelating
• 23:32
  agents, multidisciplinary care. This is a paramount for all the
• 23:37
  patients with these diseases. I think much, much more than
• 23:43
  than the gene gene therapy. So do not forget all the others,
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  which are the majority that cannot go through gene therapy,
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  at least at the moment. So improve gene therapy, but
• 23:54
  also do not forget to improve all the other treatments.
• 23:57
  Exactly. OK.
• 23:59
  And for you William, what would be the take away message?
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  I I will not repeat what Lori said, although I fully agree and
• 24:06
  I would say exactly the same. I will also underline another
• 24:10
  aspect, which is the importancy of enrolling in the registries
• 24:17
  to have the numbers, the real numbers of how many patients we
• 24:21
  have with sickle cell anemia and with just a trait, because it is
• 24:27
  important, especially in the transmission of the disease as
• 24:31
  it is a genetic disorder, right? Also the importance of research
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  and of patient participation in research.
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  So it is important to know what is happening out there and to
• 24:44
  collaborate and patients many times say, oh, there's nothing
• 24:49
  happening it there is a lot of stuff happening in the
• 24:53
  background. Only in some countries like the
• 24:56
  UK or France or the US or some countries have portals where
• 25:01
  patients can go and access and see what's going there and have
• 25:06
  access and can enroll directly in the clinical research.
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  Smaller countries have a lot more difficult.
• 25:13
  Access even. To the information, to the
• 25:15
  possibility of participation in, in the clinical trials and
• 25:19
  everything and medication comes along later on a later stage,
• 25:24
  OK, But it is important not to lose faith and to participate.
• 25:30
  And the role of patient associations is really important
• 25:34
  because they established the bridge between the research and
• 25:39
  also the healthcare providers and the patients.
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  They can help in the sharing the information, making the
• 25:49
  information available, making information more accessible.
• 25:53
  Because the clinical trial information is very technical,
• 25:57
  it's very difficult for the patient to understand and
• 26:02
  patients are entitled to having the information, but the patient
• 26:08
  association are really, really key to establishing that key to
• 26:13
  the that bridge to advocating for the patient interests and
• 26:17
  needs. So there there is one really
• 26:20
  good thing. We all like participants and
• 26:25
  patients really usually shy away from having an active role in
• 26:31
  speaking up. We need to speak up because no
• 26:34
  one will come to stand up for for us, right.
• 26:37
  So it's, it's both on the and for healthcare professionals and
• 26:42
  industry to listen to the patients and have their
• 26:46
  interests in mind as well. It's not just numbers, people
• 26:51
  are there and it is important to keep them informed and to make
• 26:55
  information easily accessible and understandable.
• 27:00
  So that was also very clear. So to get involved for the
• 27:04
  patients, both register obviously, but get involved and
• 27:10
  for obviously the clinicians and researchers to pay attention to
• 27:14
  you. Thank you very much to both of
• 27:17
  you for your time, for this fascinating discussion and yeah,
• 27:22
  for sharing your your experience with us.
• 27:26
  And thank you to all of you for tuning in and listening.