The gene-edited cell therapy had previously been under a partial clinical hold restricting pediatric enrollment to the clinical trial.
bluebird bio’s biologics license application (BLA) submission for lovotibeglogene autotemcel (lovo-cel) to treat sickle cell disease (SCD) will likely be delayed as the company awaits FDA feedback on newly submitted manufacturing compatibility data.
“We also remain laser focused on our lovo-cel BLA for sickle cell disease. Following feedback from the FDA in February, bluebird submitted additional information related to chemistry, manufacturing and controls (CMC) comparability analyses to the FDA in early March; we anticipate a response from the Agency within a matter of weeks,” Andrew Obenshain, chief executive officer, bluebird bio, said in a statement.1 “Lovo-cel is the most deeply studied gene therapy in development for sickle cell disease, with more than 50 patients treated and multiple patients followed for more than 6 years. We remain extremely confident in the quality of our BLA submission. Most importantly, we know that patients and their families are waiting, and we will move quickly to expedite our BLA submission, pending alignment with FDA on product comparability."
The FDA previously gave feedback to bluebird on vector and drug product analytical comparability evaluations the company had completed in December 2022 between the product evaluated in clinical trials and the planned product for commercial sale. bluebird expects response soon and pending alignment on product compatibility with the FDA, will file soon after. The company plans to request priority review for patients 12 and older with SCD and a history of vaso-occlusive events. If approved, bluebird continues to anticipate a commercial launch in early 2024.
“...speaking plainly, we will likely miss the Q1 2023 submission goal,” Obenshain said in a recent conference cell. “Our file is completely written and ready for submission, but we are awaiting feedback from the FDA.”
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The delay in filing is the latest roadblock for lovo-cel, which was under a partial clinical hold for a year that suspended enrollment, cell collection, conditioning, and infusion of patients under the age of 18 between December 2021 and December 2022.2 The hold was placed due to a case of persistent, non-transfusion-dependent anemia in a pediatric patient, while enrollment of adult patients continued.
Recent data related to the anemia case and an additional, later anemia case showed that these 2 patients, which had entered the trial with anemia, were the only participants with the alpha-thalassemia trait.3 This trait consists of 2 α-globin gene deletions (−α3.7/−α3.7) and has since been added to the exclusion criteria for all current studies of lovo-cel.
"An in-depth analysis of 2 cases of ineffective erythropoiesis with persistent anemia following lovo-cel treatment reassure that these cases do not have clonal evolution or an emerging malignancy," Walters Mark Walters, MD, of the University of California, San Francisco Benioff Children's Hospital, said while presenting the data.3 "The working hypothesis is that the anemia is attributable to alpha-thalassemia trait with robust HbAT87Q production.”
Lovo-cel is intended to deliver modified functional copies of βA-T87Q-globin, the disease-targeted gene, to patients’ hematopoietic stem cells (HSCs). The cells are collected from patients’ via plerixafor mobilization and apheresis, modified ex-vivo, and re-administered as a 1-time autologous HSC transplantation. Lovo-cel is being evaluated in the ongoing phase 1/2 HGB-206 (NCT02140554) clinical trial and the long-term follow-up study LTF-307 (NCT04628585) and was previously evaluated in the phase 1/2 HGB-205 clinical trial (NCT02151526).