Gene therapy may reduce, eliminate disease symptoms for patients with hemoglobinopathies

Issue: January 25, 2016

ORLANDO, Fla. — Gene therapy using autologous hematopoietic stem cells transduced with an experimental lentiviral vector improved the long-term outcomes for patients with hemoglobinopathies, according to study results presented at the ASH Annual Meeting and Exposition.

Hematopoietic stem cell gene therapy may induce production of functional beta globin in the red blood cell lineage, reducing disease symptoms among patients with hemoglobinopathies, such as sickle cell disease or beta-thalassemia major, according to study background.

Previous data from the HGB-205 study indicated CD34-positive cells transduced with LentiGlobin BB305 (Bluebird Bio Inc.) — a lentiviral vector that contains an engineered beta^A-T87Q-globin gene — induced rapid clinical improvement and lead to near-normal levels of total hemoglobin in one patient with severe sickle cell disease and two patients with beta-thalassemia major (beta⁰/beta^E).

Marina Cavazzana, MD, PhD, head of the department of biotherapy in the immunology and pediatric hematology unit at Hôpital Universitaire Necker-Enfants Malades in Paris, and colleagues provided follow-up data on these three patients, as well as data from one additional patient treated with beta-thalassemia major (beta⁰/beta⁰).

Researchers collected hematopoietic stem cells via bone marrow harvest from the patient with severe sickle cell disease and via peripheral blood apheresis from the patients with beta-thalassemia major. Patients underwent myeloablation with IV busulfan followed by infusion of the product.

As of July 31, 2015, none of the patients have experienced a drug-related adverse event. Integration site analyses have shown a high polyclonal reconstitution without clonal dominance.

The patient with severe sickle cell disease produces about 51.5% anti-sickling hemoglobin (48% HbA^T87Q, 1.8% HbF, 1.7% HbA₂) 9 months post infusion and has not been hospitalized for a sickle cell disease-related event even though transfusions ceased at day 88.

The two originally treated patients with beta-thalassemia major have been transfusion free for at least 15 months and are consistently expressing beta^A-T87Q-globin. The final patient with beta-thalassemia major has had only 1 month of post-infusion follow-up.

Total hemoglobin at last visit was 11.4 g/dL in the patient with sickle cell disease, 10.7 g/dL and 12.9 g/dL in the two originally treated patients with beta-thalassemia major, and 9.2 g/dL in the final patient treated.

HbA^T87Qlevels were 5.5 g/dL in the patient with sickle cell disease, 7.8 g/dL and 9.7 g/dL in the two originally treated patients with beta-thalassemia major, and pending in the final patient.

“Our study demonstrated the continued promise of gene therapy for both the severe sickle cell anemia patient and the patient with beta-thalassemia major,” Cavazzana said during the presentation. “The progress data presented proves the production of anti-sickling hemoglobin is able to prevent any sign of underlying disease and the patient has no more pain and can attend school full-time. He has had no hospitalization and no intake of any drug after the gene therapy procedure and he has no need of iron chelation.”

Cavazanna reported a similar status for the patient with beta-thalassemia major. – by Anthony SanFilippo

Reference:

Raetz E, et al. Abstract 202. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Disclosure: The researchers report consultant/advisory roles, speakers bureau roles and employment with; stock or other ownership in; and research funding from Bluebird Bio Inc. and Novartis.