Gene therapy shows promise as potential cure for sickle cell disease
LentiGlobin led to a reduction in hemolysis and complete resolution of severe vaso-occlusive events among a small cohort of patients with sickle cell disease, according to study results published in The New England Journal of Medicine.
LentiGlobin (bb1111; bluebird bio) is a self-inactivating lentiviral vector that encodes the human HBB variant BetaA-T87Q.
“In this therapy, we do not change or edit the gene that causes sickle cell disease. Instead, we use a viral vector to deliver a new gene that will make a healthy hemoglobin — a beta hemoglobin — into the stem cell,” Julie Kanter, MD, director of the Adult Sickle Cell Clinic at The University of Alabama at Birmingham, said in a press release. “This is like coding new instructions into the cell. The old instructions for hemoglobin S are still there, but now the cell can make HbA and HbS. The vector can deliver more than one copy of the instructions to each cell — usually between one and four copies — so the cell can make more HbA than HbS.”
Rationale and methodology
New and improved treatment options are needed for patients with sickle cell disease as this population of patients has fewer medications and therapies compared with many other diseases.
The ongoing phase 1/phase 2 study included 43 patients, 35 of whom received an infusion of LentiGlobin. The study had median follow-up of 17.3 months.
Researchers observed engraftment in all 35 patients.
Between 6 months and 36 months after infusion, median total hemoglobin level increased from a baseline level of 8.5 g/dL to 11 g/dL or higher.
Researchers found human HBB variant BetaA-T87Q made up at least 40% of total hemoglobin, and they reported a reduction in hemolysis.
The study also showed complete resolution of severe vaso-occlusive events among 25 evaluable patients, compared with a median 3.5 events per year within the 2 years prior to study enrollment.
Moreover, no cases of hematologic cancer occurred during the follow-up of 37.6 months.
“We need to make these treatments available, and we need all people with sickle cell disease to have a sickle cell doctor to make that happen,” Kanter said in the release. “We need the therapy to be affordable so that people everywhere living with this disease have the option for gene therapy. Right now, most people with sickle cell disease live in sub-Saharan Africa and in India. They do not have even the basic treatments they need, such as vaccines, penicillin or hydroxyurea that can make a huge difference in people’s lives with sickle cell disease. Eventually we need people in these areas to have equal opportunity to better outcomes.”