Date: 2018-06-15
Type of
information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 23rdCongress of the European Hematology Association (EHA)
Company: bluebird bio (USA - MA)
Product: LentiGlobin® BB305 (autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human beta A-T87Q-globin gene)
Action
mechanism:
- gene therapy/stem cell therapy. LentiGlobin BB305 Drug Product consists of autologous CD34+ hematopoietic stem cells transduced with lentiviral vector LentiGlobin BB305 encoding the human Beta A-T87Q-globin gene and suspended in cryopreservative solution.
Disease: sickle cell disease
Therapeutic
area: Genetic diseases - Hematological diseases - Rare diseases
Country: USA
Trial
details:
- HGB-206 is a Phase 1 clinical trial evaluating the safety and efficacy of bluebird bio’s LentiGlobin BB305 product candidate in subjects with severe sickle cell disease. The study is designed to enroll up to 29 subjects. Subjects will be followed to evaluate safety and efficacy, which will be measured based on changes in red cell function tests, hemolysis markers, and frequency of clinical events secondary to SCD (e.g., vaso-occlusive crises or acute chest syndrome events). (NCT02140554)
Latest
news:
-
• On June 15, 2018, bluebird bio announced new interim data from the ongoing HGB-206 Phase 1 multicenter clinical study of LentiGlobin investigational gene therapy in patients with severe sickle cell disease (SCD) will be presented at the 23rdCongress of the European Hematology Association (EHA) by Julie Kanter, M.D., Medical University of South Carolina,Charleston, South Carolina.
-
Recent Progress in Gene Therapy for Severe Sickle Cell Disease: Updated Interim Results from a Phase 1 Clinical Study of LentiGlobin Gene Therapy (Abstract S836)
-
HGB-206 is an ongoing, open-label study designed to evaluate the safety and efficacy of LentiGlobin gene therapy for 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 a refined Drug Product (DP) manufacturing process intended to increase DP vector copy number (VCN) as well as changes to 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 were also treated under the amended study protocol, but received LentiGlobin gene therapy made from stem cells collected from peripheral blood after mobilization with plerixafor rather than via bone marrow harvest. Results, as of May 15, 2018, include:
- Group C: 6 patients treated under the amended study protocol and with DP manufactured using the refined process, median (range) follow-up 3 (1.2 – 6.0) months:
- 4 of 6 patients had ? 3 months follow up, and were producing 3 – 6 g/dL of HbAT87Q by 3 months
- 1 patient was producing 8.8 g/dL of HbAT87Q and a total hemoglobin level of 14.2 g/dL at 6 months
- Median transduced CD34+ cells: 81%
- Median DP cell dose: 7.1 x 106 CD34+ cells
- Median DP VCN (copies per diploid genome): 4
- Overall safety profile remains generally consistent with myeloablative conditioning
- Continued feasibility of plerixafor mobilization and apheresis observed
- Group B: 2 patients treated under the amended study protocol and with DP manufactured using stem cells from bone marrow harvest with ? 9 months follow up:
- Patient 1312, who received LentiGlobin manufactured entirely using a refined manufacturing process, was producing 7.2 g/dL HbAT87Q and 12.8 g/dL of total hemoglobin (56% HbAT87Q) at 9 months of follow-up
- Patient 1313, who received LentiGlobin manufactured using a combination of the original and the refined manufacturing processes, was producing 3.2 g/dL HbAT87Q and 11.0 g/dL of total hemoglobin (29% HbAT87Q) at 15 months of follow-up
- Group A: Long-term data on 7 patients in the initial study cohort with ? 2 years follow-up:
- Steady levels of LentiGlobin vector and HbAT87Q were maintained through 2 years (median follow-up: 24.2 months; range: 22.8 – 32.9)
- Median transduced CD34+ cells: 25%
- Media DP cell dose: 2.1 x 106 CD34+ cells
- Median DP VCN: 0.6
- Median (range) total hemoglobin at last study visit was 9.1 (7.1 – 11.4) g/dL
- • On February 3, 2017, bluebird bio announced treatment of the first patient under the amended study protocol in HGB-206, the Phase 1 study of its LentiGlobin Drug Product in patients with severe sickle cell disease (SCD). This study now incorporates several changes to the study protocol with the goal of increasing production of therapeutic anti-sickling hemoglobin (HbAT87Q). Changes to the study protocol for HGB-206 include increasing the percentage of transduced cells through manufacturing improvements, improving myeloablation (and subsequent engraftment) by increasing the target busulfan area under the curve, introducing a minimum period of regular blood transfusions prior to stem cell collection, improved cell processing and exploring an alternate hematopoietic stem cell (HSC) procurement method. To accommodate these changes to the protocol, the study enrollment has been expanded for a total enrollment of up to 29 patients.
- • On December 6, 2015, bluebird bio announced the presentation of new data from the ongoing HGB-206 clinical study evaluating its LentiGlobin BB305 product candidate in patients with severe sickle cell disease (SCD), at the 57th American Society of Hematology Annual Meeting.
- The data from the HGB-206 study were presented during a poster session by John F. Tisdale, M.D., senior investigator, molecular and clinical hematology branch at the National Institutes of Health. This ongoing, open-label Phase 1 study is evaluating the safety and efficacy of LentiGlobin BB305 product candidate in the treatment of subjects with severe SCD. Results, as of November 17, 2015, include: Drug product has been manufactured for four patients with severe SCD, and three patients have been infused with LentiGlobin BB305. Subjects 1301 and 1303 have three and 5.3 months of follow up post-infusion, respectively.
- Drug product vector copy number (VCN) was 0.5/0.6 in Subject 1301, 1.3 in Subject 1303 and 0.6 in Subject 1306.
VCN in peripheral blood leukocytes at three months follow up was 0.04 in Subject 1301 and 0.11 in Subject 1303.
- Early data on Subjects 1301 and 1303 with at least three months of follow up show a gradual increase in HbAT87Q levels post-infusion.
- At the three-month post-infusion follow up for Subject 1301, the proportion of anti-sickling hemoglobin accounted for 17 percent of all hemoglobin production (4 percent HbAT87Q + 13 percent HbF).
- At the six-month post-infusion follow up for Subject 1303, the proportion of anti-sickling hemoglobin accounted for 16 percent of all hemoglobin production (12 percent HbAT87Q + 4 percent HbF).
- Longer follow up data and additional subjects are required to determine the extent of HbAT87Q production and clinical benefit of LentiGlobin BB305 in severe SCD.
The safety profile in the infused patients is consistent with autologous transplantation and no drug product-related grade 3 adverse events have been reported.
- • On June 13, 2015, bluebird bioannounced that the first patient with severe sickle cell disease has been infused in the HGB-206 U.S.-based clinical study at the National Institutes of Health Clinical Center in Bethesda, Maryland.
Is
general: Yes
