Bluebird bio simply can’t catch a break. Just half a year after coming off an FDA clinical hold, development of the biotech’s blood disease gene therapy has once again been halted.
The FDA slapped a partial clinical hold for bluebird’s lovotibeglogene autotemcel (lovo-cel) in sickle cell disease (SCD) patients under the age of 18, the company said Monday. Enrollment of adult patients in the drug’s ongoing clinical studies isn’t affected, bluebird added.
Just a month ago, the Cambridge, Massachusetts-based gene therapy specialist announced it planned to file lovo-cel for an FDA approval in the first quarter of 2023. The company is now evaluating if the new clinical hold would affect that timeline. The therapy, also known as LentiGlobin, works by delivering functional copies of the beta-globin gene through lentiviral vectors into a patient’s blood stem cells to produce regular red blood proteins.
The partial suspension is the result of one case of “persistent, nontransfusion-dependent anemia” following one-time treatment with lovo-cel in an adolescent patient. The inherited disease SCD is itself marked by anemia. The patient is clinically well, and there is no evidence of cancer or clonal predominance, bluebird said.
The latter part is important because it was only in June that the FDA lifted clinical holds on several LentiGlobin trials in SCD and beta thalassemia, where the product is also known as betibeglogene autotemcel (beti-cel). Those holds were implemented after reports of suspected cancers in a phase 1/2 SCD trial. One case was later rediagnosed as transfusion-dependent anemia, and bluebird’s investigation later exonerated the gene therapy for the acute myeloid leukemia case.
The latest partial clinical hold marks another dip in bluebird’s roller-coaster ride this year. In addition to the cancer scare, the company recently left the European market after hitting reimbursement setbacks that forced bluebird into a situation that president Andrew Obenshain called “untenable” for a small biotech. LentiGlobin was approved in the EU under the brand name Zynteglo for the rare blood disorder beta thalassemia.
With its decision to withdraw from Europe, despite approvals in place, Zynteglo and another newly greenlighted gene therapy called Skysona for cerebral adrenoleukodystrophy are no longer available in EU.
Applications for Zynteglo in beta thalassemia and Skysona recently won FDA priority review. As for lovo-cel’s SCD indication, bluebird recently reached an agreement with the FDA to use data from Group C of the phase 1/2 HGB-206 trial on 30 patients with at least 18 months of follow-up for a filing.
Last November, the FDA effectively pushed back lovo-cel’s filing when it requested “an analytical comparability strategy” related to the drug’s manufacturing process for the final commercial product relative to the clinical candidate. Bluebird is now assessing the comparability and expects to have results in the fourth quarter of 2022 to support a submission in early 2023.
Meanwhile, in November, bluebird spun off its oncology programs into a separate publicly traded company called 2seventy bio. The company was also the developer of the lentiviral vector used in Bristol Myers Squibb’s Abecma, which won an FDA go-ahead in March as the first BCMA-targeted CAR-T therapy to treat late-line multiple myeloma.