New Medicines

Severe sickle cell disease in patients aged 12 years and older


New molecular entity
bluebird bio
bluebird bio

Development and Regulatory status

Phase III Clinical Trials
Apr 22bluebird reconfirms it plans to file for FDA approval in Q1 23 [15].
Jan 22bluebird address the lovo-cel clinical hold, saying it had received a written question from the FDA and is still evaluating the impact the delay may have on the projected BLA submission expected in Q1 2023. [13]
Jan 22Assuming the partial hold is lifted, bluebird plans to file lovo-cel with the FDA in the US by Q1 2022 [12].
Dec 21FDA has placed lovotibeglogene autotemcel (lovo-cel) gene therapy on partial clinical hold for patients under the age of 18. The partial, temporary suspension relates to an ongoing investigation by bluebird bio into an adolescent patient with persistent, non-transfusion-dependent anemia following treatment with lovo-cel, now 18 months post-treatment [11]
Nov 21EU/UK development discontinued. bluebird plans to withdraw its regulatory marketing authorisations for Zynteglo (and Skysona) from the EU and UK by early 2022. It will continue long-term follow-up of patients previously enrolled within the European clinical trial programs as planned, but does not intend to initiate any new clinical trials in Europe for the beta-thalassemia, cerebral adrenoleukodystrophy or sickle cell disease programs [10].
Aug 21bluebird bio announce plans to focus on the US market going forward. They plan an orderly wind down of operations in Europe and to explore how to give pts in Europe access to its gene therapies, including potentially out-licensing the ex-U.S. rights to its three lead products to a company with European experience and capabilities. [9]
Jun 21MHRA awards an innovation passport. The designation means that LentiGlobin will be reviewed by using the new innovative licensing and access pathway (ILAP) introduced last December. ILAP works in a similar way to the EU PRIME pathway but adds an additional layer as it involves input from NICE and the SMC, meaning that NHS funding deliberations are bundled into the review [8].
Jun 21The FDA has lifted a clinical hold placed on bluebird bio’s sickle cell gene therapy in February, making way for the company to get a phase 1/2 trial and phase 3 study of the treatment back on track [7].
Mar 21bluebird bio announce this morning that in-house analyses demonstrate that betibeglogene autotemcel was unlikely to be the cause of AML reported in an early-stage clinical study of LentiGlobin for sickle cell disease. They have performed multiple assessments to determine where in the genome the LVV insertion occurred, and if this integration was responsible for any change in gene regulation or gene expression nearby. Multiple independent analyses have confirmed that vector insertion in the AML cells from this patient took place in the VAMP4 gene which, they say "has no known role in the development of AML or with any cellular process related to cancer". They also found no evidence of disruption to normal gene regulation or gene expression in and around the site of vector insertion. bluebird bio are in talks with the US FDA to resume clinical studies.[6]
Nov 20Discussions regarding the regulatory pathway for sickle cell anaemia have been ongoing in 2020 with the US FDA. In June, bluebird bio reported that an general agreement was reached with the FDA regarding clinical data package required to support a Biologics Licensing Application (BLA) submission for beta-globin gene therapy for sickle cell anaemia will be based on data from a portion of patients in the HGB-206 study Group C [2].
Nov 20Has orphan drug status in EU and US [2].
Sep 20EMA grants Priority Medicine (PRIME) designation to beta-globin gene therapy, for treatment of sickle cell disease. The designation was based on data reported from HGB-205, HGB-206 and LTF-303 studies [2].
Jun 20Has rare pediatric disease designation in the US for sickle cell anaemia [2].
Oct 17US FDA grants Regenerative Medicine Advanced Therapy designation to β-globin gene therapy for sickle cell anaemia [2].


A β-globin gene therapy for sickle cell anaemia and β-thalassaemia, using its proprietary lentiviral gene delivery system.
Sickle cell disease refers to the group of disorders that affects haemoglobin to form abnormal haemoglobin molecules (HbS). Sickle cell disease is thought to be the most common severe genetic disease in the UK and France, with 10,000-15,000 people affected. The prevalence of sickle cell disease is highest in sub-Saharan Africa [1].
Severe sickle cell disease in patients aged 12 years and older
Intravenous infusion

Trial or other data

Feb 21Bluebird Bio has temporarily suspended two clinical trials (HGB-206 and HGB-210) of its sickle cell disease gene therapy after one case of acute myeloid leukemia and one case of myelodysplastic syndrome were reported [5].
Nov 20PIII HGB-210 study is recruiting (NCT04293185). This is a non-randomised, open-label, multi-site, single-dose study in approximately 35 adults and pediatric subjects ≥2 and ≤50 years of age with SCD. It is recruiting at sites in the US only. Collection of primary outcome data is due to complete Nov 23 [3].
Nov 20bluebird Bio is planning a confirmatory PIII study, HGB-210 in patients with SCD and a history of VOEs over 24 months. It will be a single arm, multi-centre, global study with a primary endpoint of HbAT87Q and Total Hb. Key secondary endpoint will be reduction in severe VOEs [4].
Nov 20LG001 study was the first PI/II clinical trial of the β-globin gene therapy and was conducted in France (LG001). The trial was initiated in 2007 and enrolled 10 patients aged 5-35 years with beta-thalassaemia major or sickle cell anaemia. The earlier HPV569 Zynteglo vector was used in this trial [2].
Oct 20Long-term follow-up trial to evaluate the long-term safety and efficacy in patients with haemoglobinopathies, including beta-thalassaemia or sickle cell disease, who have been treated with ex vivo gene therapy drug product in bluebird bio-sponsored clinical studies is enrolling by invitation (LTF-303; NCT02633943). The observational trial is designed to enrol approximately 94 patients in the US, Australia, France Italy, Thailand and UK (London) and started in Sep 13. It is due to finish in Mar 31 [3].
Mar 20PI/II HGB-205 study which evaluated the safety and efficacy of β-globin gene therapy in patients with severe sickle cell anaemia or β-thalassaemia major following autologous HSCT completes (NCT02151526). This study was a continuation of LG001 study. The open-label trial enrolled seven patients in France [2,3].
Dec 18Positive efficacy, safety and immunogenicity results from the HGB-206 trial presented at the 60th Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2018) [2].
Aug 14Open-label PI/II trial to evaluate the safety and efficacy of β-globin gene therapy in patients with severe sickle cell disease starts (HGB-206; NCT02140554). The study intends to enrol 50 patients in the US. Patients in this study will be divided into three cohorts, group A were treated under the original study protocol, group B were treated under an amended study protocol that included changes intended to increase DP vector copy number (VCN) and improve engraftment of gene-modified stem cells and group C are also treated under the amended study protocol, but receive Zynteglo made from stem cells collected from peripheral blood after mobilisation with plerixafor rather than via bone marrow harvest. Participants will remain in the study for two years, before being asked to participate in a long-term follow-up study that will monitor the safety and efficacy of the treatment for up to 13 years post-transplantation [2].