Clinical trial updates

ZYNTEGLO™ (gene therapy)

  • Product Information

    Product Information

    Scientific name: beti-cel (betibeglogene autotemcel)
    Brand name: ZYNTEGLO™
    RESPONSIBLE: bluebird bio Inc.

  • Clinical Trial/Study Information

    Clinical Trial/Study Information

    Last update: 22/6/2023

    Northstar (HGB-204)

    Trial Name: Northstar (HGB-204)
    Code: NCT01745120
    Phase: 1b
    Eligible patient diagnosis: TDT (non β00 genotype, β00 genotype or IVS-I-110 mutation) (adult & paediatric/adolescent; ages 12 – 35)
    No. of Patients enrolled: 18 [6 with non β00 genotype, 8 with β00 genotype or IVS-I-110 mutation, 4 with other mutations including β++, B0+, BE+] (Last update: April 2019)
    Study Sites: 6 Sites per country

    Completion date: February 2018
    Scope of the Study / Aim: Transfusion independence post-infusion for at least 24 months
    Results & more information: Thompson A, et al (2019)

    Northstar (HGB-205)

    Trial Name: Northstar (HGB-205)
    Code: NCT02151526 
    Phase: 1b
    Eligible patient diagnosis: TDT or SCD (all genotypes) (adult & paediatric/adolescent ; ages 5 – 35)
    No. of Patients enrolled: 7 → 4 [3 with βE/β0 genotype, 1 with IVS-I110 mutation] & 3 [with SCD] (Last update: Jan 2022)
    Study Sites: 1 Sites per country

    Completion date: February 2019
    Scope of the Study / Aim: Transfusion independence post-infusion for at least 24 months
    Results & more information: Thompson A, et al (2019)


    Northstar-2 (HGB-207)

    Trial Name: Northstar-2 (HGB-207)
    Code: NCT02906202
    Phase: 3
    Eligible patient diagnosis: : TDT (non β0/β0 genotype) (adult & paediatic ; ages 0- 50)
    No. of Patients enrolled: 23 (Last update: 18/6/2023)
    Study Sites: 8 Sites per country

    Completion date: March 2022
    Scope of the Study / Aim: Transfusion independence post-infusion
    Results & more information: Locatelli F, et al (2022)


    Northstar-3 (HGB-212)

    Trial Name: Northstar-3 (HGB-212)
    Code: NCT03207009
    Phase: 3
    Eligible patient diagnosis: β0/β0 genotype or IVS-I-110 mutation (adult & paediatic ; ages 0 – 50)
    No. of Patients enrolled: 18 (Last update: 4/4/2023)
    Study Sites: 9 Sites Sites per country

    Completion date: November 2022
    Scope of the Study / Aim: Transfusion independence post-infusion

    Long-term follow-up study (LTF-303) (13 years follow up study)

    Trial Name: Long-term follow-up study (LTF-303) (13 years follow up study)
    Code: NCT02633943 
    Phase: Long-term follow-up study of Phase 1/2 studies [HGB-204, HGB-205], or Phase 3 studies [HGB-207, HGB-212]
    Eligible patient diagnosis: TDT patients who participated in HGB-204, HGB205, HGB-207, HGB-212 (ages 0 – 50)
    No. of Patients enrolled: : 66 (Last update: 6/5/2023)
    Study Sites: 15 Sites per country

    Anticipated completion date: November 2035
    Scope of the Study / Aim: After completing the parent clinical study (approximately 2 years), patients will be followed for an additional 13 years for a total of 15 years post infusion. Monitoring for malignancies, immune-related adverse events, haematologic disorders and neurologic disorders.

  • Regulatory Information

    Regulatory Information

    Status: Authorised

    Additional notable points:

    • EMA: Conditional marketing authorization for patients 12 years and older with TDT who do not have a β0/β0
      genotype (2019); marketing authorisation withdrawn from the EU at the request of the marketing authorisation holder (bluebird bio) (2022)
    • FDA: Approved to treat patients with beta-thalassemia who require regular red blood cell (RBC) transfusions (2022)
    • MHRA: Not approved (2021)

Update: 20 December 2023

  • 16 patient cell collections have been completed (7 November 2023)
  • Qualified Treatment Centre (QTC) network: 29 centres activated to date (adult & paediatric).
  • 63 patients with transfusion-dependent beta-thalassaemia had received beti-cel across 4 clinical trials (HGB-204, HGB-205, HGB-207, HGB-212) (cut-off date: 30 January 2023) and showed sustained transfusion independence and improvements in iron management for up to 9 years of follow-up. All four studies are complete, and all patients have transitioned to a long-term follow-up study (LTF-303).

New data

  • Data presented at the 65th ASH Annual Congress (9 – 12 December 2023) in San Diego (USA) showed that:
  • Among patients in the Phase 3 studies, 90.2% (37/41) achieved transfusion independence, which was maintained for up to 6 years across ages and genotypes.
  • Among patients in the Phase 1/2 studies, 68.2% (15/22) achieved transfusion independence, with 14 patients maintaining transfusion independence for up to 9 years.
  • Among 12 adult patients and 22 pediatric patients in the Phase 1/2 and Phase 3 studies, clinically meaningful improvements in quality of life were demonstrated, including various quality of life assessments for mental, physical and psychosocial health, were demonstrated in both adult and pediatric patients up to 36 months.
  • No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported.
  • Across all studies, 37/51 patients restarted chelation, and 12 received phlebotomy post-infusion; however, 69% (35/51) were able to stop chelation therapy, demonstrating restoration of iron levels over time and reduced iron management burden in those patients.

Sources: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-third-quarter-2023-financial-results-and

https://investor.bluebirdbio.com/news-releases/news-release-details/long-term-data-presented-ash-support-beti-cel-potentially

 

Update: 30 September 2023

  • 11 patient cell collections have been completed (8 August 2023)
  • Qualified Treatment Centre (QTC) network: 16 centres activated to date. Plans to have 40 – 50 centres by the end of 2023.

Source: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-second-quarter-2023-financial-results-and

 

Update: 30 June 2023

  •  First commercial ZYNTEGLO patients has been infused (9 May 2023).
  • 6 patient cell collections have been completed (9 May 2023).

Source: bluebird bio Reports First Quarter 2023 Financial Results and Highlights Operational Progress – bluebird bio, Inc.

 

Update: 31 March 2023

  • Apheresis for first commercial ZYNTEGLO patient has been completed (09 January 2023) and an additional 5 patient cell collections completed (29 March 2023).
  • Early indicators continue to demonstrate significant patient demand for ZYNTEGLO. Approximately 40 patients have initiated the insurer authorisation process. None have received a negative response (29 March 2023). The company aims to expand manufacturing capacity to meet projected demand.
  • Qualified Treatment Centre (QTC) network: 12 centres activated to –date. 30 centres are on-boarding or in negotiation. Plans to have 40 – 50 centres by the end of 2023.
  • Insurance coverage. Outcomes-based agreements are in place with 3 of the largest pharmacy benefit managers in the US, representing dozens of downstream national and regional plans with a favourable coverage policy for ZYNTEGLO.

Sources: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bioprovides-update-commercial-launch-progress-program

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bioreports-fourth-quarter-and-full-year-2022-financial

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