FDA Places Clinical Hold on LentiGlobin Gene Therapy Trials

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on all LentiGlobin gene therapy trials following an announcement that two participants with sickle cell disease (SCD) developed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), respectively.

At the time of the announcement, patient dosing had just begun in the phase III HGB-210 trial, which enrolled patients with SCD between the ages of 2 and 50 years.

The patient who was diagnosed with AML was enrolled in the Group A cohort of the phase I/II HGB-206 trial and received treatment five years ago. The diagnosis was classified as a Suspected Unexpected Serious Adverse Reaction by the FDA, meaning there is a “reasonable possibility” that LentiGlobin caused the patient to develop AML.

The patient with MDS was enrolled in Group C of HGB-206. While LentiGlobin administered to patients in Groups A and B was manufactured from stem cells derived from bone marrow harvest, the therapy administered to those in Group C was manufactured using a process designed to increase vector copy number and was derived from stem cells collected from peripheral blood after mobilization with plerixafor.

Previously, bluebird bio reported a separate occurrence of MDS in Group C of HGB-206, which the company claimed was not treatment related in a paper published in Blood Advances last year.

Sources: BioSpace, February 24, 2021; Hsieh MM, Bonner M, Pierciey FJ, et al. Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease. Blood Adv. 2020;4(9):2058-2063; ClinicalTrials.gov, NCT04293185 and NCT02140554.