The BLA, for patients aged 12 and older who have a history of vaso-occlusive events (VOE), includes a request for priority review. That means that, if granted, the FDA’s review of the application will be shortened from 10 months to six months.
Bluebell bio is targeting an early 2024 commercial launch for the therapy if approved.
Sickle cell disease (SCD) is a complex and progressive genetic disease. High concentrations of sickle hemoglobin (HbS) in red blood cells (RBCs) cause RBCs to become sickled, sticky, and rigid with a shorter life span, which manifests acutely as hemolytic anemia, vasculopathy, and vaso-occlusion.
In the US, there are 100,000 people living with SCD, and half of people with SCD do not live past the age of 40.
Bluebird bio says its BLA submission is based on data from the ‘largest and most mature clinical development program for any gene therapy in sickle cell disease’.
The submission is based on efficacy results from 36 patients in the Phase ½ HGB-206 Group C cohort with a median 32 months of follow-up and two patients in the Phase 3 HGB-210 study with 18 months of follow-up each. The BLA submission also includes safety data from 50 patients treated across the entire lovo-cel program, including six patients with six or more years of follow-up.
bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have been treated with lovo-cel in bluebird bio-sponsored clinical studies.
lovo-cell is a one-time treatment that is designed to add functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their red blood cells (RBCs) can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled RBCs, hemolysis, and other complications.
The FDA previously granted lovo-cel orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation, and rare pediatric disease designation for the treatment of SCD.
In December 2021 the FDA placed lovo-cel clinical studies on a partial hold for patients under the age of 18: relating to an investigation by bluebird bio into an adolescent patient with persistent, non-transfusion-dependent anemia following treatment with lovo-cel.
The hold was lifted at the end of last year.
“The severity of sickle cell disease, and its impact on patients and caregivers, has been underappreciated and overlooked for far too long," said Andrew Obenshain, chief executive officer, bluebird bio, as the company announced the BLA submission this morning.
"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.”
Lovo-cel submission follows Zynteglo and Skysona approvals
If approved, lovo-cel will be bluebird bio’s third ex-vivo gene therapy approved by the FDA for a rare genetic disease and its second FDA approval for an inherited hemoglobin disorder.
In August last year, the company celebrated the FDA approval of gene therapy Zynteglo (betibeglogene autotemcel) and Skysona (elivaldogene autotemcel) in September: changing the fortunes of a company that had warned just a few months prior that its financial position raised ‘substantial doubt’ about its ability to continue as a going concern.
CEO Obenshain now champions the company as a leading gene therapy company.
“"Following two milestone FDA approvals in 2022, bluebird is now emerging as a commercial gene therapy leader, fueled by strong momentum and uptake for both Zynteglo and Skysona across patients, payers and providers,” he said in the company’s FY22 earnings call last month. “We also remain laser focused on our lovo-cel BLA for sickle cell disease. “
Zynteglo, which comes with a $2.8m price tag, is on track to scale to 40-50 centers by the end of the year. Skysona, which costs $3m, remains on track for 5-10 patient starts this year as previously guided.