Top 10 for 2021: #1 | Gene Therapy for Hemoglobinopathies

Top 10 for 2021: #1 | Gene Therapy for Hemoglobinopathies

Living with a condition with no known cure is the devastating reality for those patients suffering from these genetic disorders. Hemoglobin disorders, or hemoglobinopathies, arise when an individual's beta-globin gene is dysfunctional. The most common hemoglobinopathies include sickle cell disease and thalassemia – combined, affecting an estimated 330,000 kids born worldwide every year.

Aside from a blood and bone marrow transplant, there is no cure for sickle cell disease or thalassemia – only treatment for symptom management. But latest research in the space has brought an experimental gene therapy for a cure in these patients – adding functional copies of a modified form of the beta-globin gene into a patient's own hematopoietic stem cells. The gene therapy gives patients the potential to make functional hemoglobin molecules, thus functional red blood cells.

In several ongoing studies, patients with six or more months of follow-up after treatment for sickle cell disease had median sickle cell hemoglobin levels reduced to 50% or less of total hemoglobin in the absence of blood transfusions. In thalassemia, studies of the therapy found sufficient hemoglobin production to reduce or eliminate the need for transfusion support among patients who would otherwise require chronic blood transfusions.

These results earned the therapy breakthrough designation from the FDA as the first-ever gene therapy for either of the conditions. Medical researchers are nearing approval to cure these chronic blood disorders.

William Morris, MD:
We’re now at #1 on our Top 10 Medical Innovations List, ‘Gene Therapy for Hemoglobinopathies.’ Dr. Hanna, I would love to hear your perspective about this potential cure. Can you give the audience a little bit of perspective around the current gold standard, and then we'll talk about the innovation?

Rabi Hanna, MD:
Thank you so much, Will, for inviting me to speak about this breakthrough. First I’d like to really highlight what sickle cell and thalassemia patients go through. This is a genetic disease that affect more than 20 million people worldwide and, as you heard, more than 300,000 babies are born with this. Can you imagine how they are born? Families are told, “Sorry, we don't have anything to cure your baby, but we will support you with care. We will support you with medication and blood transfusions that are good to maintain normal function for a while, but with increased pain episodes and frequent hospitalization.” For example, in sickle cell, there are more than 100,000 patients living in the United States alone with this disease – with one in every 365 African Americans affected. This is a disease that not only affects the patient, but the community as a whole.

Many of these patients, despite that they survived to their adulthood, will succumb to death and they will have a shortened life. The average life in a sickle cell patient, despite current therapies, is in the 40's and they often die from a stroke or cardiac event as this is not just a blood disease. This is a disease that affects all the vascular structures and will lead to complications that will enter the death. And what do we do? Despite the fact that it has been more than 100 years since its discovery there’s been only three medications approved in the last 50 years. Until now, we didn't have the technology to achieve this dream of a cure for everyone, so the standard included a medication called Hydroxyurea that helps to prevent the sickling of cells. But despite the adherence to this medication, we still see patients, even kids, coming in with stroke.

We also see patients who are requiring exchange of a blood every month. Still, a few years later, they may die. We have a cure called in bone marrow transplant, but only small portion of patients can undergo bone marrow transplant due to lack of matches.

Gene therapy will allow you to be able to get a transplant for your own cells. We take the cells and correct the gene through different methods that were really not available in the past, but are today through advanced technology and more research support from the NIH and from the Gates Foundation. Now the dream becomes possible that we can give a patient one-time therapy to cure them for life. That data that was presented in August at the EHA show is very promising data, with more than 90% of patients with no pain episodes, and more than 85% moving from transfusion dependent to transfusion independent.

William Morris, MD:
What's simply just dramatic is that it’s been 100 years, and we haven't moved the football down the field in terms of the medication management and symptom management. Now we have something of a potential cure. Tell us a little bit about when this will be adopted.

Rabi Hanna, MD:
I am very pleased to say that there's many pharmaceutical companies now undergoing clinical trials, and the research is in phase three. One of them is in a very late phase and applying for FDA approval and breakthrough designation. Really these studies are very complex and complicated in terms of their safety profile, both short and long-term. This innovation is really the fruit of so many decades of technology improvement, and we should not rush to it. We are hoping in 2021, that the FDA could approve some of those companies based on not only their efficacy, but the important safety outcomes for many of these trials.

William Morris, MD:
Is there any preliminary data around some of the side effect profiles that you're keeping an eye out for?

Rabi Hanna, MD:
Yeah, for sure. We are paying close attention and what we are finding is that the preliminary results are similar to the side effects we expect with high-dose chemotherapy of Busulfan (that it is given as a part of a transplant). So the side effects tend to be temporary and related to that re-eradication of the cells that are producing the sickle cell or the thalassemia. Patients spend approximately one month to six weeks in the hospital to enable the chemotherapy and get rid of the sickled cells before the normal cells make a home inside the bone marrow. So we know that side effects of this treatment are really manageable, and many of the patients can tolerate it safely.

William Morris, MD:
As an adult hospitalist, I certainly am familiar with the impact of something like sickle cell. I'm curious, will this gene therapy actually be available for adults who still have these diseases, or is it primarily reserved for pediatric patients?

Rabi Hanna, MD:
The studies to date have been done mostly in adults with the age limits as 12 to 55 in sickle cell and up to 60 in thalassemia. So I think this will be especially important for many adult patients.

William Morris, MD:
I want to thank you, Dr. Hanna, for joining us today and sharing your insights as they relate to this, our #1 medical innovation for the year 2021, “Gene Therapy for Hemoglobinopathies.”
 

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