bluebird bio Submits BLA for Sickle Cell Gene-Edited Cell Therapy, Lovo-cel

bluebird bio has submitted a biologics license application (BLA) to the FDA for lovotibeglogene autotemcel (lovo-cel) for the treatment of patients with sickle cell disease (SCD) aged 12 or older who have a history of vaso-occlusive events.¹

The BLA submission, which includes a request for priority review, is based on efficacy data from 36 patients who received lovo-cel in the ongoing phase 1/2 HGB-206 clinical trial (NCT02140554) and 2 patients treated in the phase 3 HGB-210 clinical trial (NCT04293185). The patients treated in HGB-206 have a median of 32 months of follow-up while the 2 patients from HGB-210 both have 18 months of follow-up. The safety data included in the submission comes from 50 patients treated across multiple clinical trials for lovo-cel; 6 of these patients have at least 6 years of follow-up. The serious adverse events (AEs) related to lovo-cel in this dataset include cases of anemia in 2 patients with alpha-thalassemia and leukemia (not resulting from insertional oncogenesis) in 2 patients. Nonserious AEs related to lovo-cel in this dataset include cases of infusion reactions, namely hot flush and decreased blood pressure, in 2 patients. Three of the 50 patients included in the BLA submission’s dataset have died: 1 patient died from sudden cardiac death and 2 patients died from leukemia.

“The severity of sickle cell disease, and its impact on patients and caregivers, has been underappreciated and overlooked for far too long,” Andrew Obenshain, the CEO of bluebird bio, said in a statement.¹ “Transformative therapies for this community are long overdue. We are pleased to have satisfied the Agency’s questions about comparability to enable our BLA submission, and to take this important step toward making lovo-cel available for individuals living with SCD.”

The BLA submission incorporates feedback which the company received from the FDA in February 2022 related to vector and drug product analytical comparability evaluations between the product used in clinical trials and the product the company plans to use for commercial sale.² The company responded to this feedback in March; as such, the BLA submission was delayed until the FDA responded. Prior to this delay, lovo-cel's progress was also delayed by a partial clinical hold placed on HGB-210 by the FDA that suspended enrollment, cell collection, conditioning, and infusion of patients under the age of 18 from December 2021 to December 2022.^3,4 The hold was related to a case of persistent, non-transfusion-dependent anemia in a pediatric patient. Adult patients were able to continue enrolling in the trial during this time. In March 2023, while awaiting the FDA’s response to the manufacturing compatibility data it submitted, bluebird bio stated that if the BLA is approved it expects a commercial launch of lovo-cel in early 2024.

Blue bird bio’s progress in the SCD genetic medicine space is trailing slightly behind Vertex Pharmaceuticals' and CRISPR Therapeutics’ joint efforts.⁵ The collaborating companies completed the rolling submission of their BLA for exagamglogene autotemcel (exa-cel; previously known as CTX001) several weeks ago, on April 3, 2023. Exa-cel is an ex vivo CRISPR/Cas9 gene-edited therapy intended to treat both SCD and transfusion-dependent beta thalassemia.

REFERENCES

1. bluebird bio Submits Biologics License Application (BLA) to FDA for lovotibeglogene autotemcel (lovo-cel) for Patients with Sickle Cell Disease (SCD) 12 years and Older with a History of Vaso-Occlusive Events. News release. bluebird bio, Inc. April 24, 2023. Accessed April 24, 2023. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-submits-biologics-license-application-bla-fda-0

2. bluebird bio reports fourth quarter and full year 2022 financial results and highlights operational progress. News release. bluebird bio. March 29, 2023. Accessed April 24, 2023. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-fourth-quarter-and-full-year-2022-financial

3. FDA lifts partial clinical hold for bluebird bio’s sickle cell disease (SCD) studies for patients under the age of 18. News release. bluebird bio, Inc. December 19, 2022. Accessed April 24, 2023. https://investor.bluebirdbio.com/news-releases/news-release-details/fda-lifts-partial-clinical-hold-bluebird-bios-sickle-cell

4. bluebird bio Announces Partial Clinical Hold for Patients Under 18 in Sickle Cell Gene Therapy Clinical Program. News release. bluebird bio. December 20, 2021. Accessed April 24, 2023. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-partial-clinical-hold-patients-under-18

5. Vertex and CRISPR Therapeutics Complete Submission of Rolling Biologics License Applications (BLAs) to the US FDA for exa-cel for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia. News release. Vertex Pharmaceuticals Inc; CRISPR Therapeutics. April 3, 2023. Accessed April 24, 2023. https://www.businesswire.com/news/home/20230402005036/en/