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Clinical Trials

Date: 2018-06-15

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the 23rd Annual Congress of the European Hematology Association

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 ?A-T87Q-globin gene and suspended in cryopreservative solution.

Disease: transfusion-dependent beta-thalassemia with non-Beta0/Beta0 genotypes

Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases

Country: France, Germany, Greece, Italy, Thailand, UK, USA

Trial details:

  • HGB-207 is a Phase 3, global, multi-center study designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in patients with transfusion-dependent beta-thalassemia and non-Beta 0/Beta 0 genotypes. The study is being conducted in the United States, Thailand, Germany, Italy, the United Kingdom, and France designed to evaluate the safety and efficacy of LentiGlobin drug product in patients with transfusion-dependent beta-thalassemia and non-?0/?0 genotypes. For this study, the manufacturing process by which the patient’s cells are transduced with the LentiGlobin viral vector has been improved, with the intent of increasing vector copy number and the percentage of cells successfully transduced.
  • The target enrollment of the study is 15 adult and adolescent patients and 8 pediatric patients. The study’s primary endpoint is the proportion of treated subjects who meet the definition of “transfusion independence,” defined as total hemoglobin levels of at least 9 g/dL without any red blood cell transfusions for a continuous period of at least 12 months at any time during the study. (NCT02906202).

Latest news:

  • • On June 15, 2018, bluebird bio announced that new data from the completed Phase 1/2 Northstar (HGB-204) study in adolescents and adults with transfusion-dependent ?-thalassemia (TDT) and any genotype, and its ongoing, Phase 3 Northstar-2 (HGB-207) multicenter clinical study of LentiGlobin™ investigational gene therapy in patients with TDT and non-?0/?0 genotypes, will be presented in an oral session on June 16 at the 23rd Annual Congress of the European Hematology Association by Franco Locatelli, M.D., Ph.D., of the IRCCS Ospedale Pediatrico Bambino Gesù of Rome, Italy. The aim of the ongoing Phase 3 Northstar-2 study (HGB-207) is to evaluate the efficacy and safety of LentiGlobin DP with manufacturing refinements in patients with TDT and non-?0/?0 genotypes.
  • Northstar-2 (HGB-207) results include (as of May 15, 2018):
  • 11 patients had been infused with LentiGlobin and the median follow-up was 8.5 months (range: 0.3 – 16.2 months). 7 of 8 patients are producing ? 7.6 g/dL of HbAT87Q and are maintaining total hemoglobin levels of 11.1 – 13.3 g/dL by 6 months. These 7 patients with ? 6 months follow-up remain transfusion free for 4.7 – 15.1 months.
  • For the 11 study participants, the median DP vector copy number (VCN) was 3.4 (range: 2.4 – 5.6) copies/diploid genome, and the median proportion of transduced CD34+ cells was 82% (range: 53 – 90%).
  • The safety profile of LentiGlobin to date is similar to that observed in the Northstar study, and consistent with myeloablative conditioning with single-agent busulfan. No grade 3 or higher DP-related adverse events (AE) have been observed. All study participants remain enrolled in the trial, and there have been no reports of graft-versus-host disease (GvHD).
  • • On June 23, 2017, bluebird bio announced early interim data from the ongoing Northstar-2 (HGB-207) Phase 3 clinical study of LentiGlobin drug product in patients with transfusion-dependent ?-thalassemia (TDT) and non-?0/?0 genotypes. These data will be presented by Mark Walters, M.D., UCSF Benioff Children’s Hospital, Oakland, California, in an oral session on Sunday, June 25 at the European Hematology Association (EHA) Annual Meeting in Madrid, Spain. A Phase 3 Study to Evaluate Safety and Efficacy of LentiGlobin Gene Therapy for Transfusion-Dependent ?-thalassemia in Patients with non-?0/?Genotypes: The Northstar-2 (HGB-207) Trial (Abstract S814)
  • The Northstar-2 Study is an ongoing, open-label, single-dose, international, multicenter Phase 3 study designed to evaluate the safety and efficacy of LentiGlobin drug product for the treatment of patients with TDT and non-?0/?0 genotypes. As of June 2, 2017, drug product had been manufactured for six patients. The median DP VCN for these patients was 3.0 (range: 2.4 – 4.0), compared to a median DP VCN of 0.7 (range: 0.3 – 1.5) in Northstar. Results in treated patients, aged 20-22 years, as of June 2, 2017, include:
    Patient 1 Patient 2 Patient 3
    DP VCN in each drug product lot (copies/diploid genome) 2.9 2.4 3.2, 2.4
    LVV+ cells 77% 53% 77%, 82%
    CD34+ cell dose (x106/kg) 7.0 13.6 8.1
    HbAT87Q (g/dl; at last follow-up) 9.5 1.6 4.6
    Total hemoglobin 13.3 Not reported Not reported
    Days since last transfusion 140 Not reported Not reported
    Follow-up 6 months 3 months 2 months
    • Follow-up on Patients 2 and 3 was not sufficient for total hemoglobin or days since last transfusion to be clinically relevant.
    • The safety profile to date appears consistent with autologous transplantation. No Grade 3 or higher drug-product related adverse events have been observed.
  • • On September 8, 2016, bluebird bio announced the opening of HGB-207, a Phase 3, global, multi-center study in patients with transfusion-dependent beta-thalassemia with non-Beta 0/Beta 0 genotypes. This study will incorporate the addition of bluebird bio’s transduction enhancers to the hematopoietic stem cell (HSC) manufacturing process, and will be conducted under the same Investigational New Drug application (IND) as previous studies of LentiGlobin in beta-thalassemia. In this study, the process by which the patient’s cells are transduced with LentiGlobin will be modified by the addition of two additives during the transduction step of the manufacturing process, intended to increase vector copy number and the percentage of cells successfully transduced. bluebird also intends to incorporate these transduction enhancers into the manufacturing process for HGB-206, its ongoing study of LentiGlobin in patients with severe sickle cell disease (SCD).

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