NEW YORK – Bluebird Bio on Wednesday said the US Food and Drug Administration has accepted for priority review its biologics license application (BLA) for the sickle cell disease gene therapy lovotibeglogene autotemcel (lovo-cel).
Sickle cell disease is a genetic condition in which red blood cells become hard and sticky and take on a "sickle" shape. High concentrations of sickled hemoglobin cause pain crises, anemia, organ damage, and early death in patients.
Bluebird Bio is seeking approval for lovo-cel as a one-time, ex vivo gene therapy for sickle cell disease patients ages 12 and older who have a history of vaso-occlusive events — painful episodes wherein sickled cells starve tissues of oxygen by blocking the flow of blood to them. The agency is expected to decide whether to approve the drug by Dec. 20.
Lovo-cel delivers functional copies of a modified beta-globin gene into patients' own hematopoietic stem cells. Bluebird Bio has designed the lentiviral vector-based gene therapy to produce anti-sickling hemoglobin and reduce sickled red blood cells and related complications.
In its BLA submitted in April, Bluebird included efficacy results from 36 participants in the Phase I/II HGB-206 study Group C cohort with a median 32 months of follow-up and from two patients in the Phase III HGB-210 study with 18 months of follow-up. In the Phase I/II trial, 96 percent of patients on lovo-cel experienced resolution of severe vaso-occlusive events; the two patients who received lovo-cel in the Phase III study also benefited.
The Somerville, Massachusetts-based company also submitted safety data to the FDA from 50 patients treated across the entire lovo-cel program, including six patients with six or more years of follow-up.
Bluebird attributed most adverse side effects among those patients to their underlying sickle cell disease or to busulfan conditioning. Nonserious adverse events related to lovo-cel included hot flush and decreased blood pressure in two patients, while serious treatment-related adverse events included anemia in two patients with concurrent alpha-thalassemia trait, and leukemia in another two patients, not resulting from insertional oncogenesis. Three patients died, one due to sudden cardiac death and two due to leukemia.
The FDA previously gave lovo-cel orphan drug status, fast-track designation, regenerative medicine advanced therapy designation, and rare pediatric disease designation for the treatment of sickle cell disease.
"The FDA's acceptance of our BLA for lovo-cel moves us one step closer in bringing a potentially transformative therapy to the sickle cell disease community that is long overdue, and we are grateful to the patients, caregivers, researchers, clinicians, and community leaders who have enabled this exciting milestone," Bluebird Bio CEO Andrew Obenshain said in a statement. "We look forward to working with the agency on its review."