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Gene Therapy

ZYNTEGLO (ex-Lentiglobin) gene therapy for patients with TDT


Update: 30 May 2019

  • Upon receipt of marketing authorisation from the European Commission by the end of June, Bluebird expects to launch first in Germany, followed by Italy, France and the U.K. in 2020
  • Analysts estimate prices of $900,000 in Europe and $1.2 million in the U.S. for Zynteglo
  • FDA approval is anticipated in 2020 for TDT patients
  • Treatment centers in each country will be set up and physicians trained.
  • Discussions for payment models with national health authorities will begin.




Update: 29 March 2019

  • The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines  Agency (EMA) adopted a positive opinion recommending conditional marketing authorization for ZYNTEGLO™ (autologous CD34+ cells encoding β A-T87Q-globin gene), a gene therapy for patients 12 years and older with transfusion-dependent β-thalassemia (TDT) who do not have a β00
  • ZYNTEGLO™ previously known as LentiGlobin, is the first ever gene therapy to be recommended for approval in the EU for TDT!
  • This positive opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorization for ZYNTEGLO in the
  • A final decision by the EC for ZYNTEGLO is anticipated in the second quarter (April – June) of 2019.




Update: 01 February 2019

  • The developing company has proposed an instalments model for the payment of gene therapy. This essentially entails a 20% payment up front before the gene therapy is applied and the remaining 80% to be paid if the treatment works (‘works’ needs to be specified) over a five-year period. If the treatment does not work, the 80% of the cost does not need to be paid to the company.
  • EMA approval for Europe is expected in mid-2019. Will then move on to secure market access and set up qualified treatment centres (in accordance to their own criteria) in 4 European countries in 2019 (i.e. UK, France, Germany and Italy). In 2020 these will extend to include Belgium, Netherlands, Greece, Cyprus, Israel, Sweden, Denmark, Switzerland and Austria. Exact countries are to be determined.



TIF Meeting with company representatives.


Update: 02 October 2018

  1. New data from (1) the completed Phase 1/2 Northstar (HGB-204) study in adolescents and adults with transfusion-dependent β-thalassaemia (TDT) and any genotype and (2) the ongoing Phase 3 Northstar-2 (HGB-207) multi-centre clinical study of LentiGlobin™ investigational gene therapy in patients with TDT and non-β0genotypes for the assessment of efficacy and safety were presented at the Annual Congress of the European Hematology Association (EHA), held between 14 – 17 June 2018 in Stockholm, Sweden.

The data collected over a period of more than 3 years suggest that one-time treatment with LentiGlobin may address the underlying genetic cause of TDT, with the majority of patients with TDT and non-β00 genotypes are transfusion-free and producing total hemoglobin at normal or near-normal levels.


Northstar (HGB-204) results:

  • All 18 patients have completed the primary two-year study and are continuing into the long-term follow-up study LTF-303.
  • 8 of 10 patients with non-β00genotypes were transfusion independent for a median of 33 months as of last follow-up.
  • One serious adverse event of HIV infection was reported 23 months after infusion. HIV was contracted from typical exposure and is not related to treatment with LentiGlobin. This was confirmed by two laboratory tests that differentiate between HIV and the lentivirus used in LentiGlobin. The Northstar clinical study Safety Review Committee (an independent group of experts in bone marrow transplant), determined that the HIV infection is not related to LentiGlobin treatment and therefore the benefit/risk profile of LentiGlobin treatment has not changed. This assessment that the HIV infection is not related to LentiGlobin treatment was concurred with by an independent Data Monitoring Committee (DMC) for the Northstar-2 (HGB-207) trial.

Northstar-2 (HGB-207) results:

  • 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 HbAT87Qand 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.

Source: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-presents-new-data-northstar-hgb-204-and-northstar-2


  1. Investigational LentiGlobin™ gene therapy for the treatment of transfusion-dependent β-thalassemia (TDT) was granted an accelerated assessment by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) for its upcoming marketing authorization application. Accelerated assessments can reduce the active review time of an MAA from 210 days to 150 days once it has been validated by the EMA. The company intends to submit a marketing authorization application before the end of 2018.

Source: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bios-lentiglobintm-gene-therapy-granted-accelerated


  1. The U.S. Food and Drug Administration (FDA) also granted LentiGlobin Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

Source: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bios-lentiglobintm-gene-therapy-granted-accelerated


Update: 20 December 2018

New data from the Phase 3 Northstar-2 (HGB-207) [for non β00 genotype]  and Northstar-3 (HGB-212) [for only β00 genotype] clinical studies of LentiGlobin gene therapy in the treatment of patients with transfusion-dependent β-thalassemia (TDT) were presented at the 60th Annual Meeting of the American Society of Hematology (ASH) in San Diego, held on 01 – 04 December 2018. A total of 37 paediatric, adolescents and adult patients with TDT and a non-β00 or β00 genotype, including patients with IVS-I-110 mutations, have been treated with LentiGlobin in the Northstar, Northstar-2 and Northstar-3 studies.


Northstar-2 (HGB-207) results:

  • 16 patients with non-β00genotypes (aged 8 – 34 years); 2 paediatric and 14 adolescents/adults with TDT have been treated in the Phase 3 Northstar-2 study.
  • 10 patients stopped receiving transfusions and had haemoglobin levels of 11.1 – 13.3 g/dL at the time of the last study visit (3 – 18 months post-treatment).
  • HbAT87Qlevels in these 10 patients ranged from 7.7 – 10.6 g/dL and significantly contributed to total haemoglobin (67 – 92%).
  • In 5 patients, all of whom had stopped chronic transfusions, an increase in the myeloid to erythroid ratio was observed, suggesting improvement in red blood cell production.

Northstar-3 (HGB-212) results:

  • 3 patients with TDT and a β00genotype or an IVS-I-110 mutation had been treated with LentiGlobin in the Phase 3 Northstar-3 study.
  • All 3 patients had total haemoglobin of greater than 10 g/dL at their last assessment, including 1 paediatric patient.
  • Patient 2 had their last transfusion 1.9 months post-treatment and last assessment at month six, Patient 3 had their last transfusion at 1.4 months post-treatment and last assessment at month three.




LentiGlobin gene therapy for patients with SCD


Update: 02 October 2018

Data from Phase 1 (HGB-206) multi-centre Study of LentiGlobin™ Gene Therapy in Patients with Severe Sickle Cell Disease were presented at the Annual Congress of the European Hematology Association (EHA), held between 14 – 17 June 2018 in Stockholm, Sweden.

  • 4 patients were treated under the amended study protocol (Group C).
  • 4 of 6 patients had ≥ 3 months follow up, and were producing 3 – 6 g/dL of HbAT87Qby 3 months
  • 1 patient was producing 8.8 g/dL of HbAT87Qand a total hemoglobin level of 14.2 g/dL at 6 months
  • Patients treated with the amended protocol (Group B) and the initial protocol (Group A) showed promising results at ≥ 9 months follow up and ≥ 2 years follow up respectively.

Source: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-new-interim-data-phase-1-hgb-206-study


Update: 20 December 2018

New data from patients in Group C of the ongoing open-label Phase 1/2 HGB-206 study of the LentiGlobin™ gene therapy in patients with sickle cell disease (SCD) were presented at the 60th Annual Meeting of the American Society of Hematology (ASH) in San Diego, held on 01 – 04 December 2018.

  • A total of 9 patients were treated with LentiGlobin in Group C ; data is available for 7 patients
  • 4 patients had 6 months follow up were found to be producing 8 – 8.8 g/dL  of HbAT87Q and were comparable to or exceeded the levels of sickle hemoglobin, HbS
  • These patients did not receive a blood transfusion during the follow up period (6 months) and had total haemoglobin ranging from 9.9 – 13.7 g/dL at their last visit.
  • No vaso-occlusive events were reported up to nine months post treatment (i.e. cut off date).
  • An exploratory analysis of key markers of hemolysis, including reticulocyte counts, lactate dehydrogenase (LDH) and total bilirubin concentration showed decrease compared to baseline.
  • To help assess the distribution of HbAT87Qin the red blood cells, an antibody that recognizes βS, the protein present in HbS, has been developed. Initial results from two patients treated with LentiGlobin gene therapy, who were nine months post treatment, showed that nearly all their red blood cells had lower amounts of βS than the βSS and the βSA control samples. Given that these patients were no longer receiving any blood transfusions, this suggests βS expression was reduced in these patients due to the production of HbAT87Qfollowing treatment with LentiGlobin.
  • One serious adverse event of myelodysplasia syndrome was reported in a patient who received LentiGlobin approximately three years ago in Group A. Laboratory analysis and the independent data monitoring committees, along with the treating physician agreed that this is unlikely to be related to LentiGlobin gene therapy.

 Source: http://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-presents-new-data-lentiglobin-gene-therapy-sickle


OTL-300 Gene therapy for TDT


Update: 30 May 2019

An oral presentation at the 22nd American Society of Gene & Cell Therapy (ASGCT) Annual Meeting in Washington, D.C. reported that:

  • Nine TDT patients (six pediatric and three adult), with severe phenotypes including β+/β+, β0/β+ and β0/β0, participated in the trial.
  • All nine patients met the safety endpoint of survival with follow-up ranging from 16 to 43 months (3.6 years).
  • No adverse events related to the product were reported.
  • Of the six pediatric patients treated, four achieved transfusion independence and one showed a reduction in transfusion requirement.
  • All three adult patients had a reduction in their transfusion requirements
  • One pediatric patient did not have a reduced transfusion requirement compared to pre-treatment levels at 12 months, which was attributed to poor engraftment of the gene-modified cells.

Sources: https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-clinical-proof-concept-data-gene


Update: 29 March 2019

OTL-300, an autologous ex vivo lentiviral gene therapy program being studied in individuals with transfusion-dependent beta-thalassaemia.

Data from all nine patients in this proof of concept trial is anticipated later in 2019.