Regenerative Medicine and Stem Cells Technologies

Bluebird bio announced encouraging interim results from the ongoing Phase 1 clinical trial testing its investigational gene therapy LentiGlobin for patients with severe sickle cell disease (SCD).

The results were presented at the 59th Annual Meeting of the American Society of Hematology (ASH), held Dec. 9-12 in Atlanta, Georgia.

LentiGlobin is a gene therapy that uses patients’ own hematopoietic stem cells to deliver bluebird’s LentiGlobin BB305 lentiviral vector. Once inserted in the patients’ cells, LentiGlobin BB305 leads to the production of the human beta-A-T87Q globin protein.

This protein will ensure cells overcome the shortage of globin synthesis (part of the hemoglobin molecule) – and that cells don’t acquire the sickle shape.

In the presentation, titled “Interim Results from a Phase 1/2 Clinical Study of LentiGlobin Gene Therapy for Severe Sickle Cell Disease,” researchers presented new data from the ongoing, open-label clinical trial HGB-206 (NCT02140554).

The trial, which is currently recruiting participants, is investigating the safety and efficacy of LentiGlobin in the treatment of adults with severe sickle cell disease.

Participants with severe SCD were split into three groups – A, B and C. Patients in group A received the treatment according to the trial’s original protocol: After cells are collected from the bone marrow, they are transduced with the LentiGlobin BB305 lentiviral vector, which encodes the human beta-A-T87Q globin gene.

Patients in group B received a modified protocol, approved in 2016, to increase the number of vectors introduced into cells and improve infusion of the modified stem cells.

Patients in group C are also treated according to the amended protocol, but the stem cells were collected from the blood and not from the bone marrow.

Until November 2017, 10 patients were treated and data was available for nine patients – seven from group A and two patients from group B – with a median follow-up of 21 months since the stem cell transplant.

Initial data from the two patients in group B showed they carried higher LentiGlobin vector copy number and higher peripheral vector copy number after the transplant. The time for cells’ engraftment – when the transplanted cells start growing and differentiating into healthy blood cells – was similar between group A and group B. So far, no adverse effects have been reported.

Julie Kanter, MD, of the Medical University of South Carolina, delivered the presentation at the ASH meeting.

“People with sickle cell disease have a genetic disease that causes the protein in red blood cells, called hemoglobin, to be misshapen,” she said in a press release.  “As a result of this abnormal hemoglobin, many affected individuals live with low blood counts and severe, recurrent pain crises that lead to organ damage and shortened life spans.

“It is also a disease that has been historically under-researched and under-resourced, with few treatment options beyond pain management,” Kanter said. “These early results with the revised study protocol indicate that gene therapy with LentiGlobin may allow people with SCD to produce substantial levels of normal, anti-sickling, adult hemoglobin.

“We are hopeful about the possibility that this could substantially reduce the painful and damaging crises that are a hallmark of this disease, potentially allowing patients to live longer, healthier lives,” she added.

In a poster titled “Successful Plerixafor-Mediated Mobilization, Apheresis, and Lentiviral Vector Transduction of Hematopoietic Stem Cells in Patients with Severe Sickle Cell Disease,” John Tisdale, MD, from the National Heart, Lung and Blood Institute, presented the results of extracting CD34+ hematopoietic stem cells harvested from the bone marrow, compared to harvesting them from peripheral blood using plerixafor, an immunostimulant that draws stem cells from the bone marrow to the blood.

The results showed that researchers were able to harvest a higher number of cells from peripheral blood using plerixafor – 10 million cells compared to 5 million cells from the bone marrow – and with fewer and less invasive procedures compared with the bone marrow harvest. Also, harvesting cells from the peripheral blood was associated with fewer adverse events.

“Historically, harvesting stem cells from people with SCD required bone marrow harvest, a painful approach for obtaining cells that often yields a suboptimal dose level and cell quality,” Tisdale said.

“The data we presented at ASH suggest that not only is this new approach using plerixafor mobilization generally tolerable for patients, but it may enable us to obtain a larger cell dose with a higher concentration of primitive stem cells,” he said. “Cells with this primitive phenotype are more likely to become long-term sources of gene-modified red blood cells.

“We believe that providing more primitive hematopoietic stem cells that carry more copies of the gene therapy vector may be critical to realizing the full promise of gene therapy for people with SCD, and we look forward to getting more data on this new cohort of patients in the coming months,” Tisdale added.

Reference: https://ash.confex.com/ash/2017/webprogram/Paper101288.html