Clinical Trial Updates (SCD)

Gene Therapy

Update: 30 June 2021

  • Phase 1/2 (HGB-206) and Phase 3 (HGB-210) studies of LentiGlobin gene therapy for sickle cell disease (SCD) (bb1111) were placed on a temporary suspension due to a reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML) and MDS.
  • The first patient was infused in HGB-210, a Phase 3 confirmatory study of LentiGlobin™gene therapy (bb1111) for adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD).
  • The analyses completed until March 2021, indicated that it is very unlikely the Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML) was related to the lentiviral vector. Laboratory analyses showed that the patient had significant chromosomal abnormalities and mutations in genes typically associated with the development of AML.
  • The case of MDS in a patient from Group C of the Phase 1/2 HGB-206 study of LentiGlobin gene therapy for SCD has been further assessed following the review of results from additional tests. The treating investigator has concluded this is not a case of MDS and has revised the diagnosis to transfusion-dependent anemia.
  • The US Food and Drug Administration (FDA) has lifted the clinical holds on the Phase 1/2 HGB-206 and Phase 3 HGB-210 studies of LentiGlobin for sickle cell disease (SCD) gene therapy (bb1111) for adult and pediatric patients with SCD.

Data of HGB-206 Group C presented at EHA2021 showed that patients with SCD maintain a median haemoglobin of ≥ 11g/dl for more than 6 months post-treatment with a complete reduction of VOC’s in up to 24 months of follow up.

Sources: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-temporary-suspension-phase-12-and-phase-3

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-fourth-quarter-and-full-year-2020-financial

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-provides-updated-findings-reported-case-acute

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-provides-update-severe-genetic-disease-programs-and

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-present-data-its-severe-genetic-disease-and

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-lifting-fda-clinical-hold-sickle-cell

EHA2021: Complete Resolution of Severe Vaso-Occlusive Events and Improved Pathophysiology with LentiGlobin Gene Therapy in Sickle Cell Disease (SCD): Ongoing Phase 1/2 HGB-206 Group C Study

http://investor.bluebirdbio.com/news-releases/news-release-details/treatment-investigational-lentiglobintm-gene-therapy-sickle-cell

http://investor.bluebirdbio.com/news-releases/news-release-details/magenta-therapeutics-and-bluebird-bio-announce-phase-2-clinical

 

Update: 08 January 2021

New data from the ongoing study of investigational LentiGlobin™ gene therapy (bb1111) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up

Group C Phase 1/2 HGB-206 for adult and adolescent patients with sickle cell disease (SCD) results presented at ASH2020:

  • 32 patients with up to 30.9 months of follow-up.
  • In 22 patients with six or more months of follow-up, median levels of gene therapy- derived anti-sickling hemoglobin, HbAT87Q, contribute at least 40% of total haemoglobin.
  • At last visit reported, total hemoglobin ranged from 6  –  15.1  g/dL  and  HbAT87Q levels ranged from 2.7 – 8.9 g/dL.
  • Median HbS was 50% and remained less than 60% at all follow-up tmepoints.
  • All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.
  • 19 patients with a history of severe VOEs had a complete resolution of VOEs after Month 6.
  • One patient with significant baseline SCD-related and cardiopulmonary disease died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD and that SCD-related cardiac and pulmonary disease contributed.
  • Collaboration with Magenta Therapeutics has been announced to evaluate the utility of MGTA-145 for Mobilizing and Collecting Stem Cells in Adults and Adolescents with Sickle Cell Disease. MGTA-145 in combination with plerixafor (the so far preferred mobilization regimen) has shown in a Phase 1 study that it can rapidly and reliably mobilize high numbers of functional stem cells in a single day, without the need for G-CSF. Thus potentially allowing for safer and more efficient mobilization for gene therapy to treat sickle cell disease thus achieving safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

Source: http://investor.bluebirdbio.com/news-releases/news-release-details/treatment- investigational-lentiglobintm-gene-therapy-sickle-cell http://investor.bluebirdbio.com/news-releases/news-release-details/magenta- therapeutics-and-bluebird-bio-announce-phase-2-clinical

 

Update: 05 November 2020

BIOLOGICS LICENSE APPLICATION (BLA) SUBMISSION: Estimated to be completed in late-2022 as the FDA has requested the clinical data package be based on the HGB-26 study Group C cohort as well as comparable data between healthy donors, SCD patients and the commercial lentiviral vector.

EUROPEAN MEDICINES AGENCY: LentiGlobin for SCD has been granted eligibility for the EMA Priority Medicines programme and therefore PRIME designation enabling more speedy regulatory evaluations.

FOOD AND DRUG ADMINISTRATION: LentiGlobin for SCD has received orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation.

Sources: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-third-quarter-2020-financial-results-and

http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bios-lentiglobintm-sickle-cell-disease-gene-therapy

 

Update: 25 August 2020

New data from the ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin™ gene therapy for adult and adolescent patients with sickle cell disease (SCD) show a near-complete reduction of serious vaso-occlusive crises (VOCs) and acute chest syndrome (ACS). These data were presented at the Virtual Edition of the 25th European Hematology Association (EHA25) Annual Congress.

A total of 37 patients have been treated with LentiGlobin for SCD to-date in the HGB-205 (n=3) and HGB-206 (n=34) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2) and C (n=25).

Group C Efficacy Results:

  • 25 patients were treated with LentiGlobin with up to 24.8 months of follow-up.
  • In 16 patients with six or more months of follow-up, median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Qcontributing at least 40% of total hemoglobin.
  • At last visit reported, total hemoglobin ranged from 9.6 – 16.2 g/dL and HbAT87Qlevels ranged from 2.7 – 9.4 g/dL.
  • All patients in Group C were able to stop regular blood transfusions and remain off transfusions at three months post-treatment.
  • There was a 99.5% mean reduction in annualized rate of VOC and ACS among the 14 patients who had at least six months of follow-up. These patients had a median of eight events in the two years prior to treatment.

Source: http://investor.bluebirdbio.com/news-releases/news-release-details/new-data-show-near-elimination-sickle-cell-disease-related-vaso

 

Update: 31 May 2020     

  • The clinical and commercial supply of ZYNTEGLO® for transfusion-dependent β-thalassemia (TDT) and SCD will be undertaken by Hitachi Chemical Advanced Therapeutics Solutions (USA) and Aptech Biopharma GmbH (Germany), both subsidiaries of Hitachi Chemical.
  • Follow up data of the Phase 3 HGB-207 (TDT), HGB-212 (TDT) and HGB-206 group C (SCD) studies will be presented at the EHA25 Congress in June

Sources: https://www.b3cnewswire.com/202005112066/hitachi-chemical-advanced-therapeutics-solutions-and-apceth-biopharma-gmbh-enter-into-strategic-clinical-and-commercial-manufacturing-agreements-with-bluebird-bio.html

https://sicklecellanemianews.com/2020/05/21/bluebird-bio-expands-partnership-securing-manufacture-development-lentiglobin/?utm_source=Sickle+Cell+Anemia+News&utm_campaign=2dbd27731c-RSS_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b01e3fbae8-2dbd27731c-73559237

http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-present-data-its-gene-and-cell-therapy-programs

 

Update: 31 March 2020

A new Phase 3 study of LentiGlobin for sickle cell disease (HGB-211) has been announced. This study is expected to begin enrolling patients in 2020, with a target of approximately 18 patients, ages 2-14 years with SCD and elevated stroke risk.

The primary endpoint of the study will be transcranial doppler response without transfusion.

HGB-211 is in addition to the company’s previously announced Phase 3 study (HGB-210)

Together with the phase 3 study HGB-210, HGB-211 is intended to support potential approval of LentiGlobin for SCD in pediatric patients at elevated stroke risk.

  • COVID-19 EFFECTS – The company expects that the COVID-19 pandemic will shift the timing of enrollment and completion of clinical studies by at least three months and expects timing shifts to vary by clinical trial and by program.

Sources: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-fourth-quarter-and-full-year-2019-financial

http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-provides-assessment-impact-covid-19-update-business

Update: 30 June 2021

  • The European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to ARU-1801. ARU-1801 was designated PRIME status based on clinical data from the MOMENTUM study, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, that demonstrate meaningful, durable reductions in disease burden.

Unlike investigational gene therapies and gene editing approaches which require fully myeloablative conditioning, the unique characteristics of ARU-1801 allow it to be given with reduced intensity conditioning (« RIC »). Compared to myeloablative approaches, the lower dose chemotherapy regimen underlying RIC has the potential to reduce not only hospital length of stay, but also the risk of short- and long-term adverse events such as infection and infertility. Preliminary clinical data from the MOMENTUM study, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, demonstrate continuing durable reductions in disease burden.

  • Three patients with sickle cell disease who received the investigational gene therapy ARU-1801 achieved and maintained normal hemoglobin levels, according to early results of a phase 1/phase 2 trial.

Sources: https://www.prnewswire.com/news-releases/aruvant-announces-the-european-medicines-agency-ema-granted-priority-medicines-prime-designation-to-aru-1801-for-the-treatment-of-sickle-cell-disease-301220542.html

https://www.healio.com/news/hematology-oncology/20210517/gene-therapy-for-sickle-cell-disease-shows-curative-potential?utm_source=selligent&utm_medium=email&utm_campaign=news&M_BT=5557136223742

 

Update: 08 January 2021

No update available

 

Update: 05 November 2020

Data will be presented at ASH2020 in December 2020 from the MOMENTUM study – an open-label Phase 1/2 clinical trial examining ARU-1801 as a one-time potentially curative gene therapy for individuals with sickle cell disease (SCD).

Unlike other investigational gene therapies that require fully myeloablative conditioning, ARU-1801 is given with reduced intensity conditioning (RIC), which is a lower dose chemotherapy.

Source: https://www.prnewswire.com/news-releases/aruvant-announces-updated-data-to-be-presented-in-oral-presentation-of-aru-1801-data-at-the-62nd-american-society-of-hematology-ash-annual-meeting-301166554.html

 

Update: 25 August 2020

No update available.

 

Update: 31 May 2020

No update available.

 

Update: 31 March 2020

No update available.

 

Update: 31 January 2020

The U.S. Food and Drug Administration (FDA) granted rare pediatric disease designation to ARU-1801, an experimental gene therapy for the treatment of sickle cell disease (SCD) and β-thalassaemia.

This designation means eligibility for a  priority review voucher once the FDA approves a biologics license application for ARU-1801.

Focus on delivering a modified version of the fetal haemoglobin gene, through a viral virus called lentivirus — optimized to enhance the protein’s natural oxygen-carrying ability and anti-sickling properties.

Source: https://sicklecellanemianews.com/2020/01/09/aravant-sickle-cell-therapy-gets-fda-rare-pediatric-disease-designation/

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