Bluebird Bio Temporarily Suspends SCD Gene Therapy Trials after Case of AML

Rare Daily Staff

Bluebird Bio said it has placed a temporary suspension on its phase 1/2 (HGB-206) and phase 3 (HGB-210) studies of LentiGlobin gene therapy for sickle cell disease (bb1111) after a participant was diagnosed with acute myeloid leukemia.

Shares of Bluebird fell more than 33 percent to $30.50 in response to the news.

In line with the clinical study protocols for HGB-206 and HGB-210, Bluebird placed the studies on temporary suspension following a report received last week that a patient who was treated more than five years ago in Group A of HGB-206 was diagnosed with AML.

The company is investigating the cause of this patient’s AML in order to determine if there is any relationship to the use of BB305 lentiviral vector in the manufacture of LentiGlobin gene therapy for sickle cell disease (SCD). In addition, a second suspected unexpected serious adverse reaction of myelodysplastic syndrome (MDS) in a patient from Group C of HGB-206 was reported last week to the company and is currently being investigated.

Sickle cell disease (SCD) is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin, causing red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events. For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complications—such as acute chest syndrome, stroke, and infections, which can contribute to early mortality in these patients.

LentiGlobin gene therapy for sickle cell disease (bb1111) is an experimental treatment being studied as a potential treatment for SCD. The U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy designation, and rare pediatric disease designation for LentiGlobin for SCD. LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

The company said no cases of hematologic malignancy have been reported in any patient who has received treatment with betibeglogene autotemcel for transfusion-dependent β-thalassemia (licensed as Zynteglo in the European Union and the United Kingdom). However, because it is also manufactured using the same BB305 lentiviral vector used in LentiGlobin gene therapy for SCD, the company has decided to temporarily suspend marketing of Zynteglo while the AML case is assessed.

“The safety of every patient who has participated in our studies or is treated with our gene therapies is the utmost priority for us,” said Nick Leschly, CEO of Bluebird. “We are committed to fully assessing these cases in partnership with the healthcare providers supporting our clinical studies and appropriate regulatory agencies.”

Photo: Nick Leschly, CEO of Bluebird