dm+d

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New Medicines

ZyntegloTransfusion-dependent beta thalassaemia, non-β0/β0 genotype form in adults

Information

Zynteglo
New molecular entity
bluebird bio
bluebird bio

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Recommended for approval (Positive opinion)
Yes
Yes
Jun 22FDA Cellular, Tissue, and Gene Therapies Advisory Committee vote 13 to 0 that the benefits of betibeglogene autotemcel outweigh its risks. The drug is under review to treat adolescent and pediatric patients with the rare blood disorder beta thalassemia who require regular red blood cell transfusions [40].
Jan 22US FDA extend review period for betibeglogene autotemcel for beta-thalassemia to August 2022 due to requiring more time to review additional clinical data from bluebird.[39]
Nov 21bluebird 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 [38].
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. [36]
Jul 21The EMA’s human medicines committee (CHMP) has endorsed findings of a review which concluded that there is no evidence Zynteglo causes acute myeloid leukaemia (AML). After examining all the evidence, the committee concluded it was clear that more plausible explanations for the AML cases included the conditioning treatment the patients received to clear out bone marrow cells and the higher risk of blood cancer in people with sickle cell disease. The CHMP has agreed on an update of recommendations for monitoring patients. Healthcare professionals should now check their patients for signs of blood cancers at least once a year for 15 years. The CHMP concluded that the benefits of Zynteglo continue to outweigh its risks [37].
Jul 21bluebird bio announces that the EMA PRAC has concluded that based on the review of all available data that the benefit-risk balance of medicinal products containing betibeglogene autotemcel (Zynteglo) remains favourable. bluebird bio has informed the EMA that is lifting the voluntary marketing suspension [35].
Jun 21In the US, bluebird bio announce the FDA has now lifted its clinical hold on all trials involving betibeglogene autotemcel (Zynteglo) in the US. The hold included the PIII Northstar-2 trial. The company is now working closely with study investigators and clinical trial sites to resume all study activities as soon as possible [34].
Apr 21Launch in Germany suspended. Company announcement states "reimbursement negotiations in Germany did not result in a price for Zynteglo that reflects the value of this one-time gene therapy with potential life-long benefit for people living with TDT. The price proposed by the German health authorities fails to recognize the severe burden of living with TDT or the innovation and benefit Zynteglo brings to patients who are impacted every day, throughout their lives by this severe genetic disease. Bluebird bio continues with productive negotiations across countries in Europe and we plan to continue to provide updates on the negotiation processes in the second half of 2021" [33]
Mar 21European PRAC starts review of betibeglogene autotemcel following a case of AML reported in a patient treated with a related investigational medicine using the same viral vector [32].
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.[31]
Feb 21Bluebird Bio has announced it has temporarily suspended marketing of Zynteglo as a beta-thalassemia treatment in Europe after a PI/II trial of the therapy in sickle cell disease reported a case of acute myeloid leukaemia (AML) and one of myelodysplastic syndrome (MDS). The suspension will allow time for the cases to be assessed [30].
Apr 20EMA renews the conditional marketing approval for beti-cel in the 27 member states of the EU as well UK, Iceland, Liechtenstein and Norway [29].
Feb 20bluebird bio initiates its rolling BLA submission for ß-thalassemia for approval in the US,but does not anticipate completing the submission until Q2 or Q3 2021. If completion of the BLA is mid-2021, bluebird bio may seek approval for a broader patient population, including patients with ß0/ß0 genotypes in addition to pediatric patients [29].
Jan 20Launched in Germany. University Hospital of Heidelberg is the first qualified treatment centre. bluebird has entered into value-based payment agreements with multiple statutory health insurances in Germany to help ensure patients and their healthcare providers have access to Zynteglo and that payers only pay if the therapy delivers on its promise. bluebird ’s proposed innovative model is limited to five payments made in equal instalments. An initial payment is made at the time of infusion. The four additional annual payments are only made if no transfusions for TDT are required for the patient [29].
Oct 19EMA approved the manufacturing specifications [24]
Jun 19Launch of Zynteglo will be delayed until 2020 due to manufacturing concerns raised by the EMA [23].
Jun 19Bluebird announce price of Zynteglo at €1.575 million in Europe and are offering a five-year, results-driven instalment payment plan. After the initial €315,000, patients only pay the same amount each year thereafter if they continue to respond to the therapy [22].
Jun 19A German company for the manufacturing of cell and gene therapeutics, Apceth Biopharma, has won the contract to produce Zynteglo in Europe. Bluebird has said it expects to file for FDA approval of Zynteglo by the end of the year [21].
May 19EU Conditional Marketing Authorisation granted 29/5/19; as the MA is conditional, the company is mandated to provide further data on safety and effectiveness in order to retain authorisation [20].
Mar 19Recommended for conditional EU approval by CHMP - the full indication is "treatment of patients 12 years and older with transfusion-dependent β-thalassaemia (TDT) who do not have a β0/β0 genotype, for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available". It is proposed that the medicine be administered in a qualified treatment centre by a physician with experience in HSC transplantation and in the treatment of patients with TDT. [20].
Mar 19A new market research report identifies Lentiglobin as one of seven new drugs it believes will hit sales of $1 billion or more, the so-called “blockbuster” mark, by 2023 [19].
Oct 18Filed in EU under accelerated review [15]
Dec 17HGB-207 PIII trial (NCT02906202) recruiting in the EU, including the UK. Expected primary completion Jan 2020 [14].
Sep 16Lentiglobin investigational gene therapy for transfusion-dependent beta-thalassemia accepted into European Medicines Agency’s PRIME Program. Lentiglobin is a gene therapy consisting of autologous CD34+ haematopoietic stem cells transduced ex vivo with recombinant LentiGlobin BB305 lentiviral vector. The PRIME initiative aims to optimise development plans and speed up regulatory evaluations of innovative medicines. [12].
Sep 16Bluebird bio announce that they have opened HGB-207, the first PIII study of LentiGlobin: the global multi-centre study is intended to be confirmatory in the EU and pivotal in the US, and has a target enrolment of 15 patients with transfusion-dependent beta-thalassemia and non-ß0/ß0 genotypes; primary outcome is transfusion independence [11].
Oct 15Commenting on subject 1003, Bluebird Bio note that the early clinical experience with HPV569 representes a crucial proof of concept. Data from the LG001 study are invaluable to optimize their gene therapy approach with improvements to the potency, robustness and manufacturing for the next-generation lentiviral vector, BB305 [9].
May 15After meetings with the FDA and the European Medicines Agency, Bluebird believes it has identified parallel paths forward for LentiGlobin BB305, planning to file in Europe first before making its case to US regulators. It plans to enroll two additional 15-patient trials that will follow subjects for two years with a primary endpoint of transfusion independence. Bluebird believes it can qualify for conditional EMA approval with results from the studies already underway, using the two trials yet to be launched to secure a permanent OK in the future. In the US, the company plans to hold off on filing an application until it has results from all four studies [7].
Feb 15Granted breakthrough therapy status in the US [6].
Dec 14Orphan status was granted in the EU & US for beta-thalassaemia major and intermedia in 2013 [4,5].
Dec 14PI/II in US and France [1].

Category

A β-globin gene therapy for sickle cell anaemia and β-thalassaemia, using its proprietary lentiviral gene delivery system.
1.5% (80-90 million people) of the population of the world are carriers of beta thalassaemia [3].
Transfusion-dependent beta thalassaemia, non-β0/β0 genotype form in adults
Intravenous

Further information

Yes

Trial or other data

Nov 20Results from two PII studies have previously been published in the NEJM in Apr 18 - Northstar (NCT01745120) and NCT02151526 [28].
Dec 19UK trial sites: UCL [26]
Dec 19Updated results from trials presented. Northstar-2 (NCT02906202)- 21 of 23 patients were treated and followed for a median of 11.6 months. 9/10 patients evaluable for TI had achieved it, with median weighted average Hb levels of 12.2 g/dL during TI. All nine patients continued to maintain TI for a median duration of 15.2 months. 18/20 patients with at least five months of follow-up had not received a transfusion for at least 3.5 months and total Hb was near normal in most, with the median total Hb at Months 6, 12 and 18 at 11.5 (n=17), 12.3 (n=11) and 12.2 g/dL (n=8), respectively. HbA [T87Q] levels were stable over time: 8.7 g/dL at Month 6; 9.3 g/dL at Month 12; and 9.4 g/dL at Month 18. Northstar-3 (NCT03207009) - 13 patients had a median follow-up of 8.8 months. Two patients had at least 12 months of follow-up and were evaluable for TI. Both patients, one patient with a β [0] /β [0] genotype and one pediatric patient with a β [0] /IVS-I-110 genotype, achieved TI, and continued to maintain it with Hb levels of 13.2 g/dL and 10.4 g/dL, respectively, at last visit. 9/11 patients with at least six months of follow-up did not receive a transfusion for more than three months as of last follow-up. In these patients, total Hb levels ranged from 8.3–14.2 g/dL at last visit.[25]
Feb 19Preliminary data from Northstar-2 (HGB-207, NCT02906202) is available via press release. A total of 16 patients with non-beta0/beta0 genotypes (aged 8 - 34 years) have been treated so far (2 paediatric, 14 adolescent/adult). At least three month follow up data available for 11 patients (range 3 months to 18 months post-treatment). Ten of 11 patients had stopped receiving transfusion and had haemoglobin levels of 11.1 - 13.3g/dL at the time of the last study visit. HbA-T87Q (gene-therapy derived haemoglobin) levels in these ten patients ranged from 7.7 to 10.6g/dL, and had a significant impact on total haemoglobin (67 - 92%). An exploratory analysis of bone marrow for six patients with more than 12 months of data; five of six patients have improved red blood cell production [18]. Safety data are pooled with Northstart-3 for this press release; safety profile reported to be consistent with myeloablative bisulfan conditioning. Serious adverse event of vaso-occlusive liver disease reported. One grade 3 thrombocytopenia possibly related to treatment [18].
Nov 18Primary outcome data are anticipated from three studies: PIII Northstar-2 (NCT02906202) in Jan 20; PIII Northstar-3 (NCT03207009) in Apr 21; PII NCT02151526 Feb 19. PII Northstar (NCT01745120) study completed in Feb 18 [16,17].
Jun 17Bluebird Bio reports initial data from PI/II Northstar-2 study. The company has changed the manufacturing process for the drug in order to increase the number of vector copy numbers (VCN) produced and increase the number of lentiviral vector positive (LVV+) cells—i.e., those that have had their gene sequence corrected—in the hope of making responses more consistent. The first of six patients recruited into the NorthStar-2 trial of LentiGlobin in patients with beta-thalassemia was able to completely halt regular blood transfusions within a month of treatment and saw hemoglobin levels return to normal within six months. The second patient in the trial showed a lower-than-expected result for a measure of hemoglobin production and VCN, raising the fear that the patient variability issue has not been wholly resolved. A third evaluable patient came in between the other two on the hemoglobin biomarker. Patients two and three have only been followed for three and two months, respectively, and as yet there is no data on total hemoglobin and transfusion rates. NorthStar-2 will eventually recruit 15 patients and if positive will set up possible filings for LentiGlobin in the U.S., while in Europe the drug has been accepted into the EMA´s PRME program, which allows accelerated approval, based on two earlier trials. Bluebird also reported new data from its earlier HGB-205 trial in patients with beta-thalassemia and SCD, which used the unimproved version of LentiGlobin. It showed that the two most recently treated SCD patients are showing rising levels of the hemoglobin biomarker, and evidence of early stabilization at a higher level compared to the initial cohort of patients, although they are not yet improved enough to be considered cured. The follow-up dataset also includes a beta-thalassemia patient who has gone from requiring regular transfusions to zero transfusions in the last three and a half years after a single treatment with LentiGlobin [13].
Dec 15Bluebird Bio report mixed results with LentiGlobin to date, which seems to work inconsistentlly. This may change with longer follow up [10].
Oct 15Bluebird Bio provides an update on subject 1003, a patient with beta-thalassemia major in the LG001 study using the first-generation HPV569 lentiviral vector. Following approximately seven years of transfusion independence, subject 1003 has recently required two blood transfusions after experiencing clinical symptoms of anemia. Importantly, both the expression of HbAT87Q and the vector copy number in peripheral blood leukocytes, a measure of the persistence of the gene therapy, have remained largely unchanged. The safety profile for both vectors is consistent with autologous transplantation, with no gene-therapy related serious adverse events [9].
May 15Initial data from an ongoing PI/II Northstar (HGB-204) and HGB-205 studies looked at 8 pts with beta-thalassemia who were treated with LentiGlobin. In the first 4 pts, treatment resulted in sufficient hemoglobin production to decrease the need for transfusion support among the patients. To date, LentiGlobin, has kept 2 pts transfusion free for 14 and 11 months, respectively which contributed to it acheiving breakthrough therapy status in the US [8].
Dec 14Bluebird announce data from two ongoing studies of LentiGlobin BB305. In the latest, Bluebird has dosed 5 patients with beta-thalassemia major, finding that the first two are producing increasing amounts of beta-globin and have been transfusion-free for 5 and 3 months, respectively. The remaining three subjects need more time before Bluebird can draw any conclusions on efficacy. In the second study, involving two beta-thalassemia major patients and one with severe sickle cell disease, the two previously discussed subjects are still producing beta-globin and remain free of the need for transfusions for 12 and 9 months, respectively. LentiGlobin BB305 has so far been well tolerated across both studies, with no gene therapy-related serious adverse events observed [2].
Dec 14Bluebird bio (formerly Genetix Pharmaceuticals) in collaboration with INSERM and the Hospital for Sick Children in France is developing a β-globin gene therapy for sickle cell anaemia and β-thalassaemia, using its proprietary lentiviral gene delivery system. The therapy involves harvesting CD34+ haematopoietic stem cells from the patient and introducing a globin gene before returning the cells to the patient. A lentiviral vector, LentiGlobin®, modified for optimal transfer to haematopoietic stem cells and gene expression in the adult red blood cell lineage is used to deliver the β-globin gene (βA-T87Q-globin) [1].

Evidence based evaluations

ZyntegloTransfusion-dependent thalassaemia beta, with a β0/β0 genotype form in patients of all ages

Information

Zynteglo
Licence extension / variation
bluebird bio
bluebird bio

Development and Regulatory status

Discontinued
Discontinued
Recommended for approval (Positive opinion)
Yes
Yes
Jun 22FDA Cellular, Tissue, and Gene Therapies Advisory Committee vote 13 to 0 that the benefits of betibeglogene autotemcel outweigh its risks. The drug is under review to treat adolescent and pediatric patients with the rare blood disorder beta thalassemia who require regular red blood cell transfusions [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 [9].
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. [8]
Feb 21Has orphan drug status in EU and US for TDT [4].
Feb 21In its latest annual report, bluebird states that it believes the data from our Northstar-3 study, together with data from the Northstar study and Northstar-2 study and HGB-205 study, could be sufficient to form the basis for a MAA variation submission in the EU, for the treatment of patients with TDT and β /β genotypes and patients with TDT who are less than 12 years of age [5].
Dec 19In the fourth quarter of 2019, bluebird initiated a rolling submission of a BLA in the US for beti-cel as a treatment of patients with TDT across all ages and all genotypes, which is based on data from the Northstar study, the Northstar-2 study, and the Northstar-3 study. Contingent upon successful resolution of FDA concerns arising out of the safety events in our SCD program, we currently expect to complete our BLA submission for beti-cel in mid-2021 [5].
Apr 18Also has breakthrough status in US [4].
Apr 18FDA grants fast track status to betibeglogene for TDT [4].

Category

A β-globin gene therapy for sickle cell anaemia and β-thalassaemia, using its proprietary lentiviral gene delivery system.
1.5% (80-90 million people) of the population of the world are carriers of beta thalassaemia. Normal genotype is β2/β2; β-thalassaemia trait has genotype -/β2 (slightly anaemic, clinically asymptomatic); β thalassaemia intermedia has genotype -/βo or β+/β+ (anaemic, very low MCV and MCH, splenomegaly, variable bone changes, variable transfusion dependency) and β thalassaemia major has genotype -o/-o (severe haemolytic anaemia, hepatosplenomegaly, chronic transfusion dependency) [1].
Transfusion-dependent thalassaemia beta, with a β0/β0 genotype form in patients of all ages
Intravenous infusion

Trial or other data

Dec 21PIII study (NCT02906202; n=23) in adult and paediatric patients found betibeglogene autotemcel therapy resulted in transfusion independence (weighted average haemoglobin level of ≥9g per deciliter without red-cell transfusions for ≥12 months) in 91%, with a safety profile consistent with that of busulfan-based myeloablation [10].
Jun 21The FDA has lifted the clinical hold on the PIII Northstar-3 trial. The company is working closely with study investigators and clinical trial sites to resume all study activities as soon as possible [7].
Mar 21bluebird bio reported that the suspected unexpected adverse reaction of AML reported in the HGB-206 study of LentiGlobin for SCD was very unlikely to be related to the BB305 lentiviral vector [7].
Feb 21bluebird bio temporarily suspended its global PIII Northstar-3 study (HGB-212; EudraCT2016-003611-35; NCT03207009) when the US FDA placed a clinical hold on all trials involving betibeglogene autotemcel following suspected serious adverse reaction (AML) due to lentiviral vector BB305 reported in the HGB-206 study of LentiGlobin for sickle cell disease [6].
Feb 21bluebird reports that in June 2020, it presented the updated clinical data from the Northstar-3 study at the 25th European Hematology Association (EHA) Annual Congress. Fifteen patients (nine β /β , three β /β , three homozygous IVS-I-110 mutation) had been treated, with a median follow up period of 14.4 months (ranging from 1.1 to 24.0 months). Six of eight evaluable patients achieved transfusion independence, with median weighted average total Hb levels of 11.5 g/dL (ranging from 9.5 to 13.5 g/dL), and continued to maintain transfusion independence for a median duration of 13.6 months (ranging from 12.2 to 21.2 months) as of the data cutoff. Eighty-five percent of patients (11 out of 13) with at least seven months of follow-up had not received a transfusion in more than seven months at time of data cutoff. These eleven patients previously required a median of 18.5 transfusions per year (ranging from 11.0 to 39.5 transfusions per year). In these patients, gene therapy-derived HbA supported total Hb levels ranging from 8.8 to 14.0 g/dL at last visit [5].
Nov 20Recruitment finishes and treatment completes in PIII Northsar-3 [2,4].
Jun 19bluebirdbio releases data from the PIII Northstar-3 study. As of April 12, 2019, 11 patients with TDT and a ß0/ß0 genotype or an IVS-I-110 mutation had been treated. The one patient evaluable for TI achieved and maintained it and had a total Hb of 13.6 g/dL at the Month 16 follow-up. Five patients had stopped transfusions for at least three months and had Hb levels of 10.2–13.6 g/dL at the time of the last study visit (5 – 16 months post-treatment). Of these patients, all of those who reached six months of follow-up (n=4) had HbAT87Q levels of at least 8 g/dL [3].
Jun 17PIII Northstar-3 study to evaluate the efficacy and safety of beta-globin gene therapy (Zynteglo; BB 305), in adult, adolescent and paediatric patients with transfusion-dependent beta-thalassaemia with a ß0/ß0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype starts (HGB-212; NCT03207009). The open label, single arm trial is enrolling 18 patients aged up to 50 years in the US, UK (at UCL hospital), Greece, Italy, France and Germany. Primary outcome is proportion of subjects who meet the definition of transfusion independence (Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion); collection of these data is due to complete Jun 22 [2].

Zynteglo Transfusion-dependent thalassemia beta, with a non-β0/β0 genotype form - in children aged up to 11 years weighing at least 6kg

Information

Zynteglo
Licence extension / variation
bluebird bio
bluebird bio

Development and Regulatory status

Discontinued
Discontinued
Recommended for approval (Positive opinion)
Yes
Yes
Jun 22FDA Cellular, Tissue, and Gene Therapies Advisory Committee vote 13 to 0 that the benefits of betibeglogene autotemcel outweigh its risks. The drug is under review to treat adolescent and pediatric patients with the rare blood disorder beta thalassemia who require regular red blood cell transfusions [7].
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 [6].
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. [5]
Feb 21Has orphan drug status in EU and US [4].
Feb 21In its latest annual report, bluebird states that it believes the data from its Northstar-3 study, together with data from the Northstar study and Northstar-2 study and HGB-205 study, could be sufficient to form the basis for a MAA variation submission in the EU, for the treatment of patients with TDT and β /β genotypes and patients with TDT who are less than 12 years of age [4].
Dec 19In the fourth quarter of 2019, bluebird initiated a rolling submission of a BLA in the US for beti-cel as a treatment of patients with TDT across all ages and all genotypes, which is based on data from the Northstar study, the Northstar-2 study, and the Northstar-3 study. Contingent upon successful resolution of FDA concerns arising out of the safety events in its SCD program, it currently expects to complete the BLA submission for beti-cel in mid-2021 [4].
Apr 18Also has breakthrough status in US [4].
Apr 18FDA grants fast track status to betibeglogene for TDT [4].

Category

A β-globin gene therapy for sickle cell anaemia and β-thalassaemia, using its proprietary lentiviral gene delivery system.
1.5% (80-90 million people) of the population of the world are carriers of beta thalassaemia. Normal genotype is β2/β2; β-thalassaemia trait has genotype -/β2 (slightly anaemic, clinically asymptomatic); β thalassaemia intermedia has genotype -/βo or β+/β+ (anaemic, very low MCV and MCH, splenomegaly, variable bone changes, variable transfusion dependency) and β thalassaemia major has genotype -o/-o (severe haemolytic anaemia, hepatosplenomegaly, chronic transfusion dependency) [1].
Transfusion-dependent thalassemia beta, with a non-β0/β0 genotype form - in children aged up to 11 years weighing at least 6kg
Intravenous infusion

Trial or other data

Nov 20Recruitment finishes and treatment completes in PIII Northstar-3 [2,3].
Jun 19bluebirdbio releases data from the PIII Northstar-3 study. As of April 12, 2019, 11 patients with TDT and a ß0/ß0 genotype or an IVS-I-110 mutation had been treated. The one patient evaluable for TI achieved and maintained it and had a total Hb of 13.6 g/dL at the Month 16 follow-up. Five patients had stopped transfusions for at least three months and had Hb levels of 10.2–13.6 g/dL at the time of the last study visit (5 – 16 months post-treatment). Of these patients, all of those who reached six months of follow-up (n=4) had HbAT87Q levels of at least 8 g/dL [3].
Jun 19In PI/II HGB-205 study, all four patients with TDT remained free of chronic transfusions after receiving beta-globin gene therapy. Patient 1201 (ß0/ßE genotype) was free of transfusions for 45.2 months with total haemoglobin of 10.1g/dL, of which 6.7 g/dL was HbAT87Q. Patient 1202 (ß0/ßE genotype) was free of transfusions for 40.1 months with total haemoglobin of 12.9g/dL, of which 10.1g/dL was HbAT87Q. Patient 1206 (ß0/ßE genotype) was free of transfusions for 23.8 months with total haemoglobin of 11.1g/dL, of which 8g/dL was HbAT87Q. Patient 1203, who is homozygous for the severe ß+ mutation IVS1-110, was free of transfusions for 20.9 months with total hemoglobin of 8.7g/dL, of which 6.7g/dL was HbAT87Q. Therapeutic phlebotomy was initiated in three of four patients (1201, 1202 and 1206) were able to begin therapeutic phlebotomy, and patient 1202 subsequently discontinued iron chelation and phlebotomy [3].
Feb 19PI/II HGB-205 study completes [2].
Jun 17PIII Northstar-3 study to evaluate the efficacy and safety of beta-globin gene therapy (Zynteglo; BB 305), in adult, adolescent and paediatric patients with transfusion-dependent beta-thalassaemia with a ß0/ß0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype starts (HGB-212; NCT03207009). The open label, single arm trial is enrolling 18 patients aged up to 50 years in the US, UK (at UCL hospital), Greece, Italy, France and Germany. Primary outcome is proportion of subjects who meet the definition of transfusion independence (Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion); collection of these data is due to complete Jun 22 [2].
Jun 13PI/II trial to evaluate the safety and efficacy of beta-globin gene therapy (Zynteglo; BB305) in patients with either beta-thalassemia major or severe sickle cell disease starts (HGB-205; NCT02151526). The open-label study will enrol seven patients aged 5 to 35 years in France. Primary outcome is number of treated participants with successful neutrophil and platelet engraftment at 24 months; collection of these data is due to complete Feb 19 [2].