A 13-year-old boy with sickle cell disease showed no signs of the disease and resumed normal activities 15 months after an infusion of LentiGlobin BB305, according to a study conducted in France and published in The New England Journal of Medicine.

Outcomes in this patient provide further supportive evidence to our previously reported results of patients who underwent a similar ex-vivo gene therapy procedure for beta thalassemia with the same BB305 vector or the previous HPV569 vector, Jean-Antoine Ribeil, MD, PhD, of the department of biotherapy at Necker Childrens Hospital in Paris, and colleagues wrote. In addition to the patient with sickle cell disease described here, under this same clinical protocol, four patients with transfusion-dependent beta thalassemia have received LentiGlobin BB305 [Bluebird Bio] and had no clinically significant complications and no longer require regular transfusions.

Approximately 90,000 people in the United States have sickle cell disease, and more than 275,000 infants worldwide are born with the disease each year.

Granted breakthrough therapy designation by the FDA in 2015, LentiGlobin BB305, is a self-inactivating lentiviral vector that encodes the human HBB variant BetaA-T87Q. This lentiviral vector mediates the addition of an antisickling beta-globin gene into autologous hematopoietic stem cells.

Ribeil and colleagues obtained bone marrow twice from the patient to collect sufficient stem cells for gene transfer and backup. Anemia was the only grade 3 adverse event reported during these procedures.

Researchers then transduced bone marrowenriched CD34positive cells with the LentiGlobin BB305 vector. The mean vector copy numbers for the two batches of transduced cells were 1 and 1.2 copies per cell.

The patient underwent myeloablation with IV busulfan (total busulfan area under the curve, 19,363 mol/minute). After a 2-day washout period, transduced CD34positive cells were infused and red-cell transfusions continued after transplantation until a large proportion of beta-globin chain of adult hemoglobin (HbA)T87Q was detected.

Neutrophil engraftment was achieved on day 38 after transplantation, and platelet engraftment was achieved on day 91 after transplantation. Within 3 months, gene markings in whole blood, CD15 cells, B cells and monocytes had stabilized. Researchers observed more gradual increases in levels of vector-bearing T cells.

HbAT87Q cells increased steadily to 5.5g/dL at month 9 and 5.7 g/dL at month 15 and red-cell transfusions were discontinued on day 88.

The patient was discharged on day 50. By more than 15 months after transplantation, no sickle cell diseaserelated clinical events or hospitalization had occurred, and all medications, including for pain management, were discontinued.

The patient experienced expected grade 3 to grade 4 adverse events of neutropenia, anemia, thrombocytopenia and infection with Staphylococcus epidermidis.

The patient reported full participation in normal academic and physical activities, Ribeil and colleagues wrote.

Researchers noted their finding were consistent with early results reported with 18 other patients with thalassemia who received LentiGlobin BB305 and that longer follow-up is required to confirm the efficacy, durability and safety observed in the study.

In an accompanying perspective, Keith Wailoo, PhD, Townsend Martin professor of history and public affairs at Woodrow Wilson School of Public and International Affairs in Princeton, New Jersey, wrote that findings on the benefits of crizanlizumab (SEG101, Novartis) and gene therapy represent new chapters in treating sickle cell disease.

Patients with sickle cell disease have come a long way from their clinical obscurity 100 years ago, Wailoo wrote. The search for a magic bullet continues, though most clinicians acknowledge that therapies wont cure the disease but merely enhance long-term management. by Chuck Gormley

Disclosure: Bluebird Bio funded the study. Ribeil reports personal fees from Bluebird Bio during the conduct of the study, grant support from AddMedica, and nonfinancial support from Novartis and Vitalaire outside the submitted work. The researchers report no relevant financial disclosures. Wailoo reports no relevant financial disclosures.

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Gene therapy product shows early promise in sickle cell disease - Healio