Gene Therapy LentiGlobin Granted Priority Medicines Designation for SCD in EU

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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EMA PRIME designation for LentiGlobin

Bluebird Bio’s investigational gene therapy LentiGlobin has been granted priority medicines (PRIME) designation by the European Medicines Agency (EMA) for the treatment of sickle cell disease (SCD).

Given to candidate therapies with promising clinical data for diseases of high unmet medical need, the designation is designed to speed clinical development and review of medicines, helping them to reach patients earlier.

“The PRIME designation shows that the EMA recognizes the importance of bringing innovative medicines to patients with SCD efficiently and will allow us to work even more closely with the Agency to help expedite the development and review of LentiGlobin for SCD,” Anne-Virginie Eggimann, senior vice president of regulatory science at Bluebird Bio, said in a press release.

LentiGlobin is a gene therapy designed to increase the levels of hemoglobin, the protein in red blood cells that carries oxygen and is defective in people with SCD due to mutations in the HBB gene.

Specifically, the therapy delivers a modified, but functional, copy of the HBB gene into a patient’s red blood cell precursors, or hematopoietic stem cells.

Once matured, the red blood cells start producing an anti-sickling version of hemoglobin, called HbAT87Q. The gene therapy is expected to lower the proportion of defective hemoglobin in the red blood cells, ultimately preventing their destruction and other complications associated with SCD.

Also, since a patient’s own blood stem cells are modified, these cells should be able to produce normal red blood cells throughout a patient’s life, allowing the treatment to be delivered as a single dose.

The EMA’s decision was based on promising data from the clinical program of LentiGlobin, including the completed HGB-205 Phase 1/2 trial (NCT02151526) and the ongoing HGB-206 Phase 1/2 trial (NCT02140554), and their long-term follow-up study, LTF-303 (NCT02633943).

HGB-205 assessed the safety and efficacy of LentiGlobin in seven patients, ages 5–35, including three with severe SCD and four with the blood disorder transfusion-dependent β-thalassemia (TDT).

Results from the SCD patients, ages 13–21, showed that the gene therapy induced HbAT87Q production in all three patients, with levels reaching 50% of total hemoglobin in one patient after a median follow-up of 31.7 months. The remaining two patients had not yet reached the 30% of anti-sickling hemoglobin predicted to have therapeutic impact, but their follow-up was still short at 6.1 and 3.4 months.

In TDT patients, most of their hemoglobin was HbAT87Q after a median follow-up of 49.6 months (about four years). All four patients remained free of transfusions shortly after LentiGlobin treatment.

The HGB-206 trial is testing the safety and efficacy of LentiGlobin in a larger population of severe SCD patients. It enrolled about 50 participants, ages 12 to 50, who were split into three groups — A, B, and C.

Patients in group A were treated per the original trial protocol, meaning that their cells were collected from the bone marrow and modified to carry the human beta-A-T87Q globin gene.

Patients in groups B and C, however, received an amended treatment protocol, designed to increase the number of viral vectors — which carry the gene — introduced into cells and improve infusion of the modified stem cells. In group B, HSCs were also extracted from the bone marrow. Patients in group C had their stem cells taken from blood.

Previous results from groups A and B up to three years after treatment showed that LentiGlobin resulted in sustained high levels of HbAT87Q — present in more than 70% of red blood cells — and reduced the frequency of vaso-occlusive crises (VOCs) and acute chest syndrome.

The latest updated results from patients in group C showed that after a minimum follow-up of six months, levels of HbAT87Q made up at least 40% of their total hemoglobin, and that this rise was sustained.

These patients also reported no cases of serious VOCs or acute chest syndrome, and all became free from regular blood transfusions as early as three months post-treatment.

Markers of red blood cell destruction were also reduced with LentiGlobin, and the therapy’s safety profile was consistent with previous reports, with no treatment-related serious adverse events.

“Based on the results from our clinical studies to date, we believe LentiGlobin for SCD has the potential to provide truly meaningful outcomes for people living with SCD,” Eggimann said.

In addition to the recent PRIME designation, LentiGlobin has also received orphan drug designation from the U.S. Food and Drug Administration (FDA) and the European Commission, as well as the FDA’s fast track, regenerative medicine advanced therapy, and rare pediatric disease designations for the treatment of SCD.

Based on the latest data, Bluebird is planning to submit an application to the FDA requesting the approval of LentiGlobin for SCD in the second half of 2021.

The company is also examining the safety and efficacy of LentiGlobin in the HGB-210 Phase 3 clinical trial (NCT04293185). This U.S.-based study is recruiting approximately 35 people, ages 2 to 50, with SCD. More information on contacts and locations is available here.