The FDA has placed a partial clinical hold on the program for patients that are under the age of 18 after an adolescent patient developed persistent anemia.
bluebird bio's sickle cell disease gene therapy program has been placed on partial clinical hold following a report of persistant anemia in an adolescent patient.
The temporary suspension of the lovotibeglogene autotemcel (lovo-cel) gene therapy program, which affects patients under the age of 18, was issued by the FDA after an adolescent patient developed persistent, non-transfusion-dependent anemia 18 months after treatment with lovo-cel. bluebird bio is conducting an ongoing investigation.
Notably, there’s no evidence of malignancy or clonal predominance and the patient is doing well clinically.
“The safety of patients treated with our gene therapies is always our top priority,” Richard Colvin, MD, Chief Medical Officer, bluebird bio said in a statement. “Consistent with the FDA’s direction, we have paused enrollment and treatment of patients younger than 18 in our SCD clinical program, and we will continue to work collaboratively with the FDA to understand and address their concerns.”
Bluebird bio plans to continue with follow-up on previously treated patients from HGB-206 and HGB-210 as well as enroll and treat new adult patients with lovo-cel through study HGB-210.
The company will work quickly to respond to the FDA’s written questions that are anticipated in early 2022 in hopes of resolving the partial hold as soon as possible. Bluebird bio is evaluating if the partial clinical hold has had any impact on first quarter 2023 projected timing for the lovo-cel biologics license application (BLA) submission.
All patients in HGB-206 Group C, who will form the primary basis of efficacy for approval, have been treated with the demonstration of analytical comparability and validation of the company’s manufacturing process as the key remaining actions prior to submission of the planned biologics license application.
Lovotibeglogene autotemcel, or lovo-cel, gene therapy is being studied as an investigational one-time treatment for sickle cell disease. The method of the treatment is to add functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic stem cells (HSCs).
Then, a patient’s red blood cells can produce anti-sickling hemoglobin (HbAT87Q), reducing the proportion of sickle hemoglobin (HbS). Ideally, the amount of sickled red blood cells decrease and the risk of hemolysis and other complications is lowered.
The FDA previously lifted clinical holds placed on several gene therapy programs from bluebird bio following the demonstration that its lentiviral vector BB305 was not associated with cancer in patients enrolled in clinical trials for sickle cell disease, including the phase 1/2 HGB-206 and phase 3 HGB210 trials for LentiGlobin for SCD as well as the phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies of betibeglogene autotemcel (beti-cell; Zynteglo) for patients with transfusion-dependent β-thalassemia.
Recently, the FDA accepted bluebird bio’s Biologics License Application (BLA) for betibeglogene autotemcel (beti-cel) for the potential treatment of β-thalassemia. The gene therapy, which will receive priority review, has a PDUFA date of May 20, 2022.