FDA Lifts Partial Clinical Hold for Bluebird’s Sickle Cell Disease Studies for Patients Under the Age of 18
December 19, 2022
The U.S. Food and Drug Administration lifted its partial clinical hold for patients under the age of 18 in studies evaluating Bluebird Bio’s experimental gene therapy lovo-cel for sickle cell disease.
“We are working closely with study investigators and clinical trial sites to resume enrollment and treatment of pediatric and adolescent patients in the first quarter of next year,” said Richard Colvin, chief medical officer at Bluebird Bio.
People with sickle cell disease (SCD) have a mutation that alters hemoglobin, the protein in red blood cells that carries oxygen to cells throughout the body. The sickle mutation causes red blood cells to have an abnormal sickle or crescent shape, which makes them inefficient in their oxygen-carrying capacity and leads to chronic anemia, vaso-occlusive crises with severe pain, multi-organ damage, complications like stroke, and a shortened life expectancy. Globally, 300,000 people are born with sickle cell disease every year, and approximately 100,000 people are living with sickle cell disease in the United States.
Lovo-cel (lovotibeglogene autotemcel) gene therapy is an investigational one-time treatment being studied for sickle cell disease 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.
In December 2021, lovo-cel clinical studies were placed on a partial hold for patients under the age of 18. The hold related to an investigation by Bluebird into an adolescent patient with persistent, non-transfusion-dependent anemia following treatment with lovo-cel.
Results from a detailed investigation of this case were presented at the American Society of Hematology Annual Meeting and Exposition on December 10, 2022, alongside details from another case of persistent anemia in an adult patient following treatment with lovo-cel. Both patients had two α-globin gene deletions (−α3.7/−α3.7), also known as alpha-thalassemia trait, and notably are the only patients in the study with this specific genotype. Following these cases, this genotype was added to exclusion criteria for ongoing studies.
Enrollment and dosing for adult patients 18 and older in the HGB-210 study continued as planned while the partial hold was ongoing for patients under the age of 18; the company is working to resume enrollment and treatment of patients ages 2-17 consistent with the study protocol. Bluebird remains on track to submit a Biologics License Application (BLA) to the FDA for lovo-cel in the first quarter of 2023.
Bluebird bio’s clinical development program for lovo-cel includes the completed phase 1/2 HGB-205 and ongoing phase 1/2 HGB-206 and phase 3 HGB-210 studies. 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.
As previously communicated, the company has completed treatment of all patients in HGB-206 Group C, which will form the primary basis for efficacy in its lovo-cel BLA submission and expects to complete vector and drug product analytical comparability studies for the lovo-cel BLA in the fourth quarter of 2022.
The FDA previously granted orphan drug, fast track, regenerative medicine advanced therapy (RMAT), and rare pediatric disease designations for lovo-cel.
Author: Rare Daily Staff
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