RARE Daily

FDA Grants Bluebird Bio Priority Review for SCD Gene Therapy

June 21, 2023

Rare Daily Staff

The U.S. Food and Drug Administration granted Bluebird Bio priority review for its lovo-cel one-time gene therapy for individuals with the rare blood condition sickle cell disease ages 12 and older who have a history of vaso-occlusive events.

The agency is expected to act on the application by December 20, 2023.

Sickle cell disease (SCD) is a complex and progressive genetic condition associated with debilitating and unpredictable pain crises, anemia, irreversible damage to vital organs, and early death. In SCD, 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. Pain onset can be sudden and unpredictable, often requiring hospitalization. About 50 to 60 percent of adults with sickle cell disease have end organ damage, with 24 percent experiencing damage in multiple organs, and one in four patients have a stroke by the age of 45.

Lovo-cel (lovotibeglogene autotemcel) gene therapy is designed to treat the underlying cause of SCD through the addition of a functional gene that enables production of anti-sickling adult hemoglobin.  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 for people who have been treated with lovo-cel in bluebird bio-sponsored clinical studies.

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, building on more than a decade of leadership in gene therapy.

The FDA’s Priority Review designation is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions, and targets a review timeline of six months from the time of filing, compared to a standard review timeline of 10 months. The agency previously granted lovo-cel orphan drug designation, fast track designation, regenerative medicine advanced therapy designation, and rare pediatric disease designation.

“The burden that people living with SCD and their families live with today is staggering. Beyond extreme pain crises that send patients to the hospital, SCD progression is associated with grave long-term consequences,” said Andrew Obenshain, CEO of Bluebird Bio. “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.”

The BLA for lovo-cel is based on efficacy results from 36 patients in the HGB-206 study Group C cohort with a median 32 months of follow-up and two patients in the 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, which is the longest follow-up of any gene therapy program for SCD.

As of August 2022, serious adverse events related to lovo-cel included anemia in two patients (4 percent) with concurrent alpha-thalassemia trait, and leukemia in two patients (4 percent), not resulting from insertional oncogenesis. Three of 50 patients (6 percent) died, one due to sudden cardiac death and two due to leukemia. The majority of adverse events in treated patients were attributed to underlying sickle cell disease or conditioning with busulfan. Nonserious adverse events related to lovo-cel included infusion reactions (hot flush and decreased blood pressure) in two patients (2 percent each).

Photo: Andrew Obenshain, CEO of Bluebird Bio

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