LentiGlobin treatment-derived hemoglobin HbAT87Q equals or exceeds sickling hemoglobin (HbS) levels in Group C patients at six months post treatment
Total hemoglobin levels stable after month three and reach range of 9.9 – 13.7 g/dL in patients who are at least six months post treatment
No reports of vaso-occlusive events in Group C patients at up to nine months post treatment with LentiGlobin
SCD is a serious, progressively debilitating and life-threatening genetic disease. SCD results from production of abnormal sickle hemoglobin (HbS), which leads to sickled red blood cells (RBCs) and hemolysis.
“After patients with sickle cell disease were treated with LentiGlobin
they began to produce gene-therapy derived HbAT87Q, which was
associated with lower levels of sickling hemoglobin, the type of
hemoglobin that damages red blood cells,” said
Many patients with SCD live with severe anemia and vaso-occlusive events which include severe, recurrent pain crises that lead to organ damage and shortened life span.
“Before receiving treatment with LentiGlobin, patients in this study
experienced frequent vaso-occlusive events, which is not uncommon for
people living with sickle cell disease,” said
HGB-206: Phase 1/2 Study of LentiGlobin for Sickle Cell Disease
HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for the treatment of adults with SCD. A total of nine patients were treated with LentiGlobin in Group C in HGB-206. As of the data cut-off of
A refined LentiGlobin manufacturing process intended to increase vector copy number (VCN) as well as changes to improve engraftment of gene-modified stem cells, was used for Group C. Group C patients also received LentiGlobin gene therapy made from hematopoietic stem cells (HSCs) collected from peripheral blood after mobilization with plerixafor rather than via bone marrow harvest.
HGB-206: Group C Efficacy
In patients who were six months post treatment (n=4), the production of gene therapy-derived hemoglobin, HbAT87Q, ranged from 4.8 – 8.8 g/dL and were comparable to or exceeded the levels of sickle hemoglobin, HbS. These patients did not receive a blood transfusion during this time and had total hemoglobin ranging from 9.9 – 13.7 g/dL at their last visit.
No vaso-occlusive events were reported as of the data cut-off (up to nine months post treatment with LentiGlobin). In an exploratory analysis, key markers of hemolysis, including reticulocyte counts, lactate dehydrogenase (LDH) and total bilirubin concentration had decreased compared to baseline.
To help assess the distribution of HbAT87Q in the red blood cells, bluebird bio has developed an antibody that recognizes βS, the protein present in HbS.
Using this antibody, the amount of βS was measured in the red blood cells obtained from healthy donors (βA/βA), sickle cell trait donors (βS/βA) and patients with sickle cell disease (βS/βS). Clear and distinct distribution of βS was observed in these control samples, with highest expression in the βS/βS samples, followed by βS/βA and no expression of βS in the healthy donor (βA/βA) samples.
Initial results from two patients treated with LentiGlobin gene therapy, who were nine months post treatment, showed that nearly all their red blood cells had lower amounts of βS than the βS/βS and the βS/βA control samples. Given that these patients were no longer receiving any blood transfusions, this suggests βS expression was reduced in these patients due to the production of HbAT87Q following treatment with LentiGlobin.
As of the data cut-off date, the safety profile of LentiGlobin remains generally consistent with underlying SCD and myeloablative conditioning. A serious adverse event (SAE) of myelodysplasia syndrome was reported in a patient who received LentiGlobin approximately three years ago in Group A of the Phase 1/2 HGB-206 study. Analysis of the patient’s cells showed no evidence of vector mediated insertional oncogenesis, and the independent data monitoring committees, along with the treating physician, agreed the SAE was unlikely related to LentiGlobin gene therapy.
About LentiGlobin in Sickle Cell Disease
LentiGlobin is a one-time gene therapy being studied as a potential treatment to address the underlying genetic cause of sickle cell disease (SCD), which could increase the production of normal hemoglobin.
bluebird bio’s clinical development program for LentiGlobin includes
ongoing studies around the world with sites
in Australia, Germany, Greece, France, Italy, Thailand, the United
Kingdom and the
In addition, bluebird is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for transfusion-dependent β-thalassemia (TDT) and SCD.
In 2019, bluebird bio plans to initiate a Phase 3 study of LentiGlobin in SCD. For more information about the ongoing Phase 1/2 HGB-206 clinical study of LentiGlobin in SCD visit clinicaltrials.gov and use identifier NCT02140554.
About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built a pipeline with broad potential application in severe genetic diseases and cancer.
bluebird bio's gene therapy clinical programs include investigational treatments for cerebral adrenoleukodystrophy, transfusion-dependent β-thalassemia and sickle cell disease.
bluebird bio's oncology pipeline is built upon the company's lentiviral
gene delivery and T cell engineering, with a focus on developing novel T
cell-based immunotherapies, including chimeric antigen receptor (CAR T)
and T cell receptor (TCR) therapies. The company’s lead oncology
programs are anti-BCMA CAR T programs partnered with
bluebird bio’s discovery research programs include utilizing megaTAL/homing endonuclease gene editing technologies with the potential for use across the company's pipeline.
bluebird bio has operations in
LentiGlobin is a trademark of bluebird bio, Inc.
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s views with respect to the potential for its LentiGlobin product candidate to treat sickle cell disease. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials of LentiGlobin will not continue or be repeated in our ongoing or planned clinical trials of LentiGlobin, the risks that the changes we have made in the LentiGlobin manufacturing will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin will be insufficient to support future regulatory submissions or to support marketing approval in the US and EU, and the risk that the LentiGlobin product candidate will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the
Source: bluebird bio, Inc.