bluebird bio has announced that a recently reported suspected unexpected serious adverse reaction (SUSAR) of acute myeloid leukemia (AML) is “very unlikely” to be related to its sickle cell disease (SCD) gene therapy LentiGlobin.
In a statement released today, bluebird bio said that the analyses completed to date includes additional scientific assessments to determine if the BB305 lentiviral vector used in the gene therapy could have caused the AML case.
“In addition to our earlier findings of several well-known genetic mutations and gross chromosomal abnormalities commonly observed in AML in this patient, our latest analyses identified the integration site for the vector within a gene called VAMP4. VAMP4 has no known association with the development of AML nor with processes such as cellular proliferation or genome stability. Moreover, we see no significant gene misregulation attributable to the insertion event,” said Philip Gregory, chief scientific officer, bluebird bio.
“In totality, the data from our assessments provides important evidence demonstrating that it is very unlikely our BB305 lentiviral vector played a role in this case and we have shared with the FDA that we believe these results support lifting the clinical holds on our beta-thalassemia and sickle cell disease programmes,” he added.
In February, bluebird bio first announced that a case of AML had been reported in a patient included in group A of the phase 1/2 HGB-206 study of LentiGlobin for SCD, who was treated more than five years ago with the gene therapy.
Another SUSAR of myelodysplastic syndrome (MDS) in a patient from group C of HGB-206 was also reported, which bluebird bio is currently investigating.
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 have since 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 its statement today.
The company added that the insertion into the VAMP4 gene has had no impact on gene expression or gene regulation and has also not caused any disruption to nearby genes.
bluebird bio said that, based on the available data, it has initiated discussions with regulators to begin the process of resuming studies for both SCD and beta-thalassaemia.
Phase 3 trials of LentiGlobin have been placed on temporary hold following the SUSAR reports.
