The US Food and Drug Administration (FDA) has lifted the clinical hold placed on bluebird bio’s gene therapy trials in February this year.
This allows the company to restart the Phase I/II HGB-206 and Phase III HGB-210 trials of LentiGlobin for sickle cell disease (SCD) gene therapy (bb1111) in adult and paediatric SCD patients.
In addition, the FDA lifted the clinical hold on the Phase III Northstar-2 (HGB-207) and Northstar-3 (HGB-212) trials of betibeglogene autotemcel gene therapy (beti-cel) in adult, adolescent, and paediatric subjects with transfusion-dependent β-thalassemia (TDT).
bluebird bio severe genetic diseases president Andrew Obenshain said: “Over the past four months, we have gained deeper knowledge and understanding of the pathophysiology of sickle cell disease that will allow us to better serve patients and the broader community.
“We look forward to resuming our clinical programmes and continuing to advance toward major regulatory submissions for sickle cell disease and β-thalassemia.”
The company temporarily stopped the trials in February after two patients in the Phase I/II HGB-206 trial developed blood cancer following LentiGlobin gene therapy treatment.
One patient developed a suspected unexpected serious adverse reaction (SUSAR) of acute myeloid leukaemia (AML), while the other developed SUSAR of myelodysplastic syndrome (MDS).
bluebird bio also suspended the marketing of betibeglogene autotemcel as it uses the same BB305 lentiviral vector as LentiGlobin.
In March, a bluebird assessment found that the SUSAR of AML in LentiGlobin for SCD is ‘very unlikely’ to be associated with the BB305 lentiviral vector.
No hematologic malignancy cases were reported in patients treated with beti-cel, the company added.
In April, further assessment showed that the trial participant who was diagnosed with SUSAR of MDS had actually developed transfusion-dependent anaemia, according to the trial investigator. Based on this, the company reported a revised diagnosis for the MDS case.
bluebird bio is currently collaborating with trial investigators and sites to restart all study activities.