Bluebird to Resume LentiGlobin Trials After FDA Lifts Hold

Bluebird Bio is set to resume trials of LentiGlobin, its investigational gene therapy for sickle cell disease, after the U.S. Food and Drug Administration (FDA) lifted its clinical hold.

The company is now working closely with study investigators and clinical trial sites to resume normal activities as soon as possible.

Earlier this year, Bluebird paused its Phase 1/2 HGB-206 trial (NCT02140554) and its Phase 3 HGB-210 study (NCT04293185), both of which were testing LentiGlobin in patients with sickle cell disease (SCD). This decision was made after the company was notified that two patients who participated in HGB-206 had developed two rare forms of blood cancer: acute myeloid leukemia and myelodysplastic syndrome.

At the same time, the company paused two other Phase 3 trials — HGB-207 (NCT02906202) and HGB-212 (NCT03207009) — which were testing another gene therapy that uses the same viral vector as LentiGlobin in patients with transfusion-dependent beta-thalassemia.

Since suspending these trials, Bluebird announced results of a new analysis that indicated the acute myeloid leukemia case was unlikely the result of treatment with LentiGlobin.

More recently, trial investigators determined that the trial participant initially diagnosed with myelodysplastic syndrome did not have this type of blood cancer, but instead had transfusion-dependent anemia.

“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,” Andrew Obenshain, president of severe genetic diseases at Bluebird, said in a press release.

“We look forward to resuming our clinical programs and continuing to advance toward major regulatory submissions for sickle cell disease and beta-thalassemia,” he added.

SCD is caused by mutations in the HBB gene, which codes for part of the hemoglobin protein that transports oxygen throughout the bloodstream. These mutations lead to the production of an abnormal form of hemoglobin that sticks together inside red blood cells, changing their appearance into a sickle-like shape, and eventually destroying them.

LentiGlobin is designed to deliver a lab-made version of the HBB gene, containing instructions to make a modified, anti-sickling form of hemoglobin, to the body’s hematopoietic stem cells — cells found in the bone marrow that are able to give rise to all types of blood cells. These stem cells are collected, genetically engineered, and finally returned to the patient via a stem cell transplant.

Previous data from HGB-206 indicated that LentiGlobin was able to sustainably increase the production of anti-sickling hemoglobin in participants’ red blood cells, lower the frequency of SCD-related health complications, and reduce red blood cell destruction.

In the U.S., LentiGlobin was given fast track, orphan drug, regenerative medicine advanced therapy, and rare pediatric disease designations for the treatment of SCD. Regulatory authorities in Europe named the therapy an orphan drug and granted it a priority medicines designation for the same indication.