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Bluebird’s Zynteglo trials set to resume, putting gene therapy back on flight path to FDA filing

Bluebird Bio’s beta-thalassemia gene therapy Zynteglo has struggled to spread its wings, and a recent clinical pause certainly didn’t help. But with studies on several bluebird drugs set to resume, Zynteglo could be looking at clearer skies ahead. 

The FDA has lifted clinical holds on two phase 3 studies of bluebird’s gene therapy Zynteglo in transfusion-dependent beta-thalassemia (TDT), the company said Monday. The move follows a trial pause earlier this year that also covered bluebird’s investigational gene therapy LentiGlobin, currently running through phase 1/2 and phase 3 studies in sickle cell disease (SCD).

The regulator has also given the biotech the all-clear to restart the studies of LentiGlobin. Bluebird says it’s “working closely” with investigators and trial sites to resume its assessments “as soon as possible.”

In February, the phase 1/2 SCD trial for LentiGloblin yielded two suspected blood cancer cases—one of acute myeloid leukemia (AML) and one of myelodysplastic syndrome (MDS). Bluebird has since reported that it’s “very unlikely” the AML diagnosis is linked to the BB305 lentiviral vector used to deliver the gene therapy, while the MDS diagnosis has been revised to transfusion-dependent anemia.

Zynteglo was immune to those blood cancer concerns, but its two late-stage trials were also put on pause because the drug is made using the same lentiviral vector as LentiGlobin. At the same time, bluebird elected to stop selling Zynteglo in Europe, where it’s already suffered a bumpy rollout.

In its clinical trial update, Bluebird didn’t specify whether it plans to resume selling the drug in Europe. 

The drug won conditional approval to treat TDT in Europe back in mid-2019, but bluebird pushed the launch into 2020 after it got word from regulators that it needed to “tighten up” manufacturing on the gene therapy.

Then the COVID-19 pandemic hit, forcing bluebird to further put off dosing of its first commercial patient in Europe, which it predicted would happen by the end of 2020. In early February, a patient in Germany received the first commercial infusion of Zynteglo, bluebird said in an update on its 2020 financial performance. 

Zynteglo isn’t yet approved in the U.S., though the company says it aims to submit its rolling Biologics License Application in beta-thalassemia by the middle of the year. The FDA has blessed Zynteglo with both an Orphan Drug tag and Breakthrough Therapy designation in TDT. 

Meanwhile, Zynteglo has continued to stall in Europe, including its first launch country Germany, where Bluebird recently failed to reach a reimbursement deal with local health authorities. The move prompted Bluebird to withdraw the drug from the German market and draw up plans to “reduce and reshape” its workforce in the region. The company planned an undisclosed number of layoffs.