FDA lifts clinical hold on bluebird bio’s LentiGlobin studies

The US Food and Drug Administration (FDA) has lifted the clinical holds on numerous studies evaluating its gene therapy LentiGlobin for sickle cell disease (SCD) and beta-thalassemia.

In February, bluebird bio said that it had received reports of a suspected unexpected serious adverse reaction (SUSAR) of myelodysplastic syndrome (MDS) in a patient from group C of the phase 1/2 HGB-206 study of LentiGlobin (betibeglogene autotemcel; beti-cel) for SCD.

At the same time, bluebird bio said that another SUSAR of acute myeloid leukaemia (AML) had been reported in the HGB-206 study – as a result, the FDA placed clinical holds on the gene therapy.

bluebird bio later announced that after further assessment following the review of results from additional tests of the MDS case, the treating investigator has concluded the patient did not have MDS and revised the diagnosis instead to transfusion-dependent anaemia.

bluebird bio also reported in March that it is ‘very unlikely’ that the SUSAR of AML was related to the BB305 lentiviral vector (LVV) used for LentiGlobin gene therapy.

According to bluebird bio, laboratory analyses suggested that the AML patient had significant chromosomal abnormalities and mutations in the RUNX1 and PTPN11 genes detected in that patient's leukemic cells.

Although preliminary findings suggested that the BB305 lentiviral vector was present in the AML blast cells, multiple independent analyses confirmed that vector insertion in the AML cells took place in the VAMP4 gene.

This gene has ‘no known role’ in the development of AML or any cellular process related to cancer, bluebird bio said in a statement.

Now, the FDA has given the green light to bluebird bio to restart the HGB-206 study and the phase 3 HGB-210 of LentiGlobin for SCD, as well as the phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies of betibeglogene autotemcel  (marketed as Zynteglo in the EU and UK) for adult, adolescent and paediatric patients with transfusion-dependent beta-thalassemia (TDT).

“Patient safety continues to be our utmost priority, and we are grateful for the close partnership with the FDA, investigators, scientists and most importantly, patients, who all contributed to the assessments of the adverse events in HGB-206 that ultimately led to today’s announcement,” said Andrew Obenshain, president, severe genetic diseases, bluebird bio.

“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 beta-thalassemia,” he added.