Busulfan role in Bluebird’s woes could impact gene therapy sector

Cell and gene therapy developers will have a close eye on cancer cases linked to Bluebird Bio’s LentiGlobin, say analysts.

Earlier this month Bluebird halted two trials of LentiGlobin in sickle cell disease – specifically HGB 206 NCT02140554 and HGB 210 NCT04293185.

It said the decision was prompted by a case of acute myeloid leukemia (AML) in a patient in group A of the Phase I/II HGB-206 study and a case of myelodysplastic syndrome (MDS) in a patient in Group C of the HGB-206 trial.

Bluebird said it was investigating various potential causes, from the BB305 lentiviral vector used to manufacture the product though to parts of the dosing regimen used in the trials.

The firm also halted European sales of Zynteglo, its beta-thalassemia therapy, on the basis that it is “manufactured using the same BB305 lentiviral vector used in LentiGlobin.”

On February 23, Bluebird announced that “the FDA has placed our clinical studies of LentiGlobin for SCD on clinical hold.”

It added that the EMA has paused the renewal procedure for Zynteglo’s conditional marketing authorization while its pharmacovigilance risk assessment committee reviews the product.

Wider implications

Bluebird’s comments about the BB305 vector’s potential role drew considerable attention.

However, for others the chemotherapy agent busulfan – which is used in the treatment regimen for both LentiGlobin and Zynteglo – was the focus.

As a medicine busulfan is used to treat chronic myelogenous leukemia. It works by slowing or stopping the growth of cancerous cells.

In cell and gene therapy busulfan is widely used as a conditioning agent in combination with other drugs to destroy the bone marrow and cancer cells in preparation for a bone marrow transplant.

A link to busulfan would be problem for the sector according to RBCCM’s Luca Issi, who pointed out that it is also used by CRISPR Therapeutics, Beam Therapeutics, Intellia Therapeutics and Sangamo Therapeutics.

He warned that if Bluebird finds busulfan is the cause “The whole field will need to slow down as the FDA will ask for longer term data.”