On August 17, 2020 bluebird bio, Inc. (Nasdaq: BLUE) reported that new data from the clinical development program for its investigational elivaldogene autotemcel (eli-cel, Lenti-D) gene therapy in patients with cerebral adrenoleukodystrophy (CALD), including data from the Phase 2/3 Starbeam study (ALD-102) and available data from the Phase 3 ALD-104 study, will be presented at the 46th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2020), taking place virtually from August 29 – September 1, 2020.
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New Cerebral Adrenoleukodystrophy (CALD) Data at EBMT 2020
Lenti-D hematopoietic stem cell gene therapy stabilizes neurologic function in boys with cerebral adrenoleukodystrophy (ALD-102 and ALD-104)
Presenting Author: Dr. Jörn-Sven Kühl, Department of Pediatric Oncology, Hematology and Hemostaseology, Center for Women’s and Children’s Medicine, University Hospital Leipzig
Poster Session & Number: Gene Therapy; ePoster O077
Additional bluebird bio data at EBMT 2020 includes encore presentations from the company’s CALD, sickle cell disease (SCD), transfusion-dependent β-thalassemia (TDT) and multiple myeloma programs.
Cerebral Adrenoleukodystrophy (CALD) Encore Data at EBMT 2020
Outcomes of allogeneic hematopoietic stem cell transplant in patients with cerebral adrenoleukodystrophy vary by donor cell source, conditioning regimen, and stage of cerebral disease status (ALD-103)
Presenting Author: Dr. Jaap Jan Boelens, Chief, Pediatric Stem Cell Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center
Poster Session & Number: Haemoglobinopathy and inborn errors; ePoster O106
Multiple Myeloma Correlative Encore Data at EBMT 2020
Markers of initial and long-term responses to idecabtagene vicleucel (ide-cel; bb2121) in the CRB-401 study in relapsed/refractory multiple myeloma
Presenting Author: Dr. Ethan G. Thompson, Bristol Myers Squibb
Poster Session & Number: CAR-based Cellular Therapy – clinical; ePoster A089
Sickle Cell Disease (SCD) Encore Data at EBMT 2020
LentiGlobin for sickle cell disease (SCD) gene therapy (GT): updated results in Group C patients from the Phase 1/2 HGB-206 study
Presenting Author: Dr. Markus Y. Mapara, Director, Adult Blood and Marrow Transplantation Program, Columbia University Medical Center
Oral Session & Number: Inborn Errors; O080
Date & Time: September 1, 2020; 4:35 – 4:42 PM CET/10:35 – 10:42 AM ET
Transfusion-Dependent β-Thalassemia (TDT) Encore Data at EBMT 2020
Clinical outcomes following autologous hematopoietic stem cell transplantation with LentiGlobin gene therapy in the Phase 3 Northstar-2 and Northstar-3 studies for transfusion-dependent β-thalassemia
Presenting Author: Professor Franco Locatelli, Director, Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù
Poster Session & Number: Gene Therapy; ePoster O074
LentiGlobin gene therapy treatment of two patients with transfusion-dependent β-thalassemia (case report)
Presenting Author: Dr. Mattia Algeri, Department of Pediatric Oncohematology – Transplantation Unit and Cell Therapies, Ospedale Pediatrico Bambino Gesù
Poster Session & Number: Haemoglobinopathy and inborn errors; ePoster A328
Cross Indication Encore Data at EBMT 2020
Safety of autologous hematopoietic stem cell transplantation with gene addition therapy for transfusion-dependent β-thalassemia, sickle cell disease, and cerebral adrenoleukodystrophy
Presenting Author: Dr. Evangelia Yannaki, Director, Gene and Cell Therapy Center, Hematology Department, George Papanicolaou Hospital
Poster Session & Number: Gene Therapy; ePoster O078
Abstracts outlining bluebird bio’s accepted data at EBMT 2020 are available on the Annual Meeting website. On August 29, 2020, at 12:30 PM CET/6:30 AM ET, the embargo will lift for ePosters and oral presentations accepted for EBMT 2020. Presentations will be available for virtual viewing throughout the duration of the live meeting and content will be accessible online following the close of the meeting until November 1, 2020.
About elivaldogene autotemcel (eli-cel, Lenti-D gene therapy)
In July 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) granted an accelerated assessment to eli-cel gene therapy for cerebral adrenoleukodystrophy (CALD). bluebird bio is currently on track to submit the Marketing Authorization Application (MAA) in the EU for eli-cel for CALD by year-end 2020, and the Biologics License Application (BLA) in the U.S. in mid-2021.
bluebird bio is currently enrolling patients for a Phase 3 study (ALD-104) designed to assess the efficacy and safety of eli-cel after myeloablative conditioning using busulfan and fludarabine in patients with CALD. Contact [email protected] for more information and a list of study sites.
Additionally, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-304) for patients who have been treated with eli-cel for CALD and completed two years of follow-up in bluebird bio-sponsored studies.
The Phase 2/3 Starbeam study (ALD-102) has completed enrollment. For more information about the ALD-102 study visit: www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT01896102.
Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that is estimated to affect one in 21,000 male newborns worldwide. Approximately 40 percent of boys with ALD will develop CALD, the most severe form of ALD. CALD is a progressive neurogenerative disease that involves breakdown of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. Symptoms of CALD usually occur in early childhood and progress rapidly, if untreated, leading to severe loss of neurologic function, and eventual death, in most patients.
The European Medicines Agency (EMA) accepted eli-cel gene therapy for the treatment of CALD into its Priorities Medicines scheme (PRIME) in July 2018, and previously granted Orphan Medicinal Product designation to eli-cel.
The U.S. Food and Drug Administration (FDA) granted eli-cel Orphan Drug status, Rare Pediatric Disease designation, and Breakthrough Therapy designation for the treatment of CALD.
Eli-cel is not approved for any indication in any geography.
About idecabtagene vicleucel (ide-cel; bb2121)
Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem. Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.
In addition to the pivotal KarMMa trial evaluating ide-cel in patients with relapsed and refractory multiple myeloma, bluebird bio and Bristol Myers Squibb’s broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.
In July 2020, Bristol Myers Squibb (BMS) and bluebird bio submitted the Biologics License Application for ide-cel to the U.S. Food and Drug Administration for the treatment of adult patients with multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Ide-cel is the first CAR T cell therapy submitted for regulatory review to target BCMA and for multiple myeloma.
Ide-cel was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and PRIority Medicines (PRIME) designation, as well as Accelerated Assessment status, by the European Medicines Agency for relapsed and refractory multiple myeloma.
Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between BMS and bluebird bio.
Ide-cel is not approved for any indication in any geography.
About LentiGlobin for Sickle Cell Disease
LentiGlobin for sickle cell disease (SCD) is an investigational gene therapy being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the ongoing Phase 1/2 HGB-206 study and the ongoing Phase 3 HGB-210 study.
bluebird bio 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 betibeglogene autotemcel and LentiGlobin for SCD. For more information visit: View Source or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.
SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive crises (VOCs). For adults and children living with SCD, this means painful crises and other life-altering or life-threatening acute complications—such as acute chest syndrome (ACS), stroke and infections. If patients survive the acute complications, vasculopathy and end-organ damage, resulting complications can lead to pulmonary hypertension, renal failure and early death; in the U.S. the median age of death for someone with sickle cell disease is 43 – 46 years.
LentiGlobin for SCD received Orphan Medicinal Product designation from the European Commission for the treatment of SCD.
The U.S. Food and Drug Administration (FDA) granted Orphan Drug status and Regenerative Medicine Advanced Therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for the treatment of SCD.
bluebird bio reached general agreement with the U.S. Food and Drug Administration (FDA) that the clinical data package required to support a Biologics Licensing Application (BLA) submission for LentiGlobin for SCD will be based on data from a portion of patients in the HGB-206 study Group C that have already been treated. The planned submission will be based on an analysis using complete resolution of severe vaso-occlusive events (VOEs) as the primary endpoint with at least 18 months of follow-up post-treatment with LentiGlobin for SCD. Globin response will be used as a key secondary endpoint.
bluebird bio anticipates additional guidance from the FDA regarding the commercial manufacturing process, including suspension lentiviral vector. bluebird bio announced in a May 11, 2020 press release it plans to seek an accelerated approval and expects to submit the U.S. BLA for SCD in the second half of 2021.
LentiGlobin for SCD is investigational and has not been approved in any geography.
About betibeglogene autotemcel (beti-cel; formerly LentiGlobin gene therapy for β-thalassemia)
The European Commission granted conditional marketing authorization (CMA) for betibeglogene autotemcel, marketed as ZYNTEGLO gene therapy, for patients 12 years and older with transfusion-dependent β-thalassemia (TDT) who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available. On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for ZYNTEGLO, supported by data from 32 patients treated with ZYNTEGLO, including three patients with up to five years of follow-up.
In the HGB-207 clinical study supporting the conditional marketing approval of ZYNTEGLO, the primary endpoint was transfusion independence (TI) by Month 24, defined as a weighted average Hb ≥9 g/Dl without any RBC transfusions for a continuous period of ≥12 months at any time during the study after infusion of ZYNTEGLO. Ten patients were evaluable for assessment of TI. Of these, 9/10 (90.0%, 95% CI 55.5-99.7%) achieved TI at last follow-up. Among these nine patients, the median (min, max) weighted average Hb during TI was 12.22 (11.4, 12.8) g/dLl.
TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.
Beti-cel adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.
Non-serious adverse events (AEs) observed during the clinical studies that were attributed to betibeglogene autotemcel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnoea, pain in extremity, and non-cardiac chest pain. Two serious adverse events (SAE) of thrombocytopenia were considered possibly related to beti-cel.
Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.
The CMA for beti-cel is valid in the 27 member states of the EU as well as UK, Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).
The U.S. Food and Drug Administration granted beti-cel Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT. Beti-cel is not approved in the United States.
Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212).
(Press release, bluebird bio, AUG 17, 2020, View Source [SID1234563718])