On December 10, 2017 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, reported that updated clinical results from HGB-206, the company’s ongoing Phase 1 multicenter study of its LentiGlobin gene therapy product candidate in patients with severe sickle cell disease (SCD), will be discussed in an oral presentation during the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, bluebird bio, DEC 10, 2017, View Source [SID1234522485]). In addition, a poster on the feasibility and potential benefits of plerixafor-mediated peripheral blood stem cell collection and drug product (DP) manufacturing in patients with SCD was presented yesterday at ASH (Free ASH Whitepaper).

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"The promising early results from the first two patients treated under the amended HGB-206 study protocol indicate that the manufacturing and patient management changes we implemented may have a meaningful impact on patient outcomes," said Dave Davidson, chief medical officer, bluebird bio. "These two patients have maintained higher levels of gene-marked cells in the blood following treatment compared to the previous patients in HGB-206. This improvement corresponds with increased production of the anti-sickling hemoglobin, HbAT87Q, made from LentiGlobin. We are hopeful that this high-level expression of HbAT87Q will lead to a sustained clinical benefit for these patients. The next group of patients in the study will be treated using LentiGlobin made from stem cells obtained from plerixafor-mobilized peripheral blood. Plerixafor mobilization in place of direct bone marrow harvest is less burdensome for patients, and our results suggest that this approach may be able to obtain a greater quantity of higher quality cells."

Interim Results from a Phase 1/2 Clinical Study of LentiGlobin Gene Therapy for Severe Sickle Cell Disease (Oral Abstract #527)
Presenter: Julie Kanter, M.D., Medical University of South Carolina, Charleston, SC
Date & Time: Sunday, December 10 at 5:30 p.m.
Location: Bldg C, Level 1, C101 Auditorium

"People with sickle cell disease have a genetic disease that causes the protein in red blood cells, called hemoglobin, to be misshapen. 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," said Dr. Kanter. "It is also a disease that has been historically under-researched and under-resourced, with few treatment options beyond pain management. 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."

HGB-206 is an ongoing, open-label study designed to evaluate the safety and efficacy of LentiGlobin DP in the treatment of adults with severe SCD. Patients in this study are divided into three cohorts: A, B and C. Patients in Group A were treated under the original study protocol. Patients in Group B were treated under an amended study protocol that included changes intended to increase DP vector copy number (VCN) and improve engraftment of gene-modified stem cells. Patients in both Group A and B had DP made from stem cells collected using bone marrow harvest. Patients in Group C are also treated under the amended study protocol, but receive LentiGlobin made from stem cells collected from peripheral blood after mobilization with plerixafor rather than via bone marrow harvest. As of November 30, 2017, ten patients had been treated in the study and follow‑up data were available on nine patients from groups A and B, with a median of 21 (6-27) months since transplantation. Key results include:

Group A
N=7

Median (min-max)

Group B
N=2

Patient 1312 Patient 1313
Transduced CD34+ cells (%) 25 (8-42)
951, 901

46, 831
Drug product Cell Dose (x106 CD34+ cells) 2.1 (1.6-5.1) 3.2 2.2
Drug product VCN (copies per diploid genome) 0.6 (0.3-1.3) 2.91, 5.01 1.4, 3.31
VCN in peripheral blood (copies per diploid genome at last measurement) 0.1 (0.1-0.2) 2.5 (M6) 0.5 (M9)
HbAT87Q (g/dL at last measurement) 0.7 (0.5-2.0) 6.4 (M6) 3.0 (M9)
HbAT87Q (% of total, at last measurement) 7.9 (5.3-18.2) 51% (M6) 28% (M9)

1 LentiGlobin DP manufactured using refined process

Both patients in Group B were treated with two DP lots. Information from each of these LentiGlobin DP lots is reflected in the chart above.
Patient 1313 received LentiGlobin manufactured using a combination of the original and the refined manufacturing processes.
Patient 1312 received LentiGlobin manufactured entirely using the refined manufacturing process.
LentiGlobin DP has been manufactured for four patients in Group C:
Median transduced CD34+ cells: 80%
Median DP cell dose: 6.9 x106 CD34+ cells
Median DP VCN (copies per diploid genome): 3.3
The first patient treated with LentiGlobin (Group C) made using plerixafor-mobilized stem cells had a VCN in peripheral blood of 2.5 at one month.
The toxicity profile observed from drug product infusion to latest follow-up was generally consistent with myeloablative conditioning with single-agent busulfan.
Successful Plerixafor-Mediated Mobilization, Apheresis, and Lentiviral Vector Transduction of Hematopoietic Stem Cells in Patients with Severe Sickle Cell Disease (Poster Abstract #990)
Presenter: John Tisdale, M.D., National Heart, Lung and Blood Institute (NHLBI), Bethesda, MD
Date & Time: Saturday, December 9 at 5:30 p.m.
Location: Bldg A, Level 1, Hall A2

"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," said Dr. Tisdale. "The data we presented at ASH (Free ASH Whitepaper) 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. 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."

Results as of November 30, 2017:

Bone Marrow Harvest Plerixafor
Number of Patients 9 (26 BMHs) 7 (10 mobilization cycles)
Adverse Events
17 Grade 3 AEs following BMH in 5 patients, 4 were SAEs (1 procedural pain, 3 SCD pain crisis)

5 Grade 3 events included 2 non-serious (hypomagnesemia and non-cardiac chest pain) and 3 SAEs (1 patient each) of SCD pain crisis
CD34+ cells collected per harvest, median (min-max) cells/kg 5.0 (0.3-10.8) x 106 10.4 (5.1-20.0) x 106

Webcast Information
bluebird bio will host a webcast at 8:30 p.m. ET today, December 10, 2017. The webcast can be accessed under "Calendar of Events" in the Investors and Media section of the company’s website at www.bluebirdbio.com.

About SCD
Sickle cell disease (SCD) is an inherited disease caused by a mutation in the beta-globin gene, that produces βS-globin. High levels of HbS in patients with SCD are responsible for the characteristic chronic anemia, vaso-occlusive crises, and other acute and chronic manifestations of SCD which lead to significant morbidity and early mortality.

Where adequate medical care is available, common treatments for patients with SCD largely revolve around prevention of infection and management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Allogeneic hematopoietic stem cell transplant (HSCT) is currently the only available option to address the underlying genetic cause of SCD, though it carries significant risk. Complications of allogeneic HSCT include a risk of treatment-related mortality, graft failure, graft versus host disease (GvHD) and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.