Type of information: Acceptation for review of a NDA
Product name: Lentiglobin®
Compound: autologous CD34+ haematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta A-T87Q-globin gene
Therapeutic area: Genetic diseases- Hematological diseases - Rare diseases
- gene therapy/stem cell therapy. Haematopoietic stem cells are taken from the patient. To make this medicine, the cells are modified by a lentivirus that carries normal copies of the beta-globin gene into the cells. When these modified cells are transplanted back into the patient, they are expected to develop into healthy red blood cells that produce beta globins that can be assembled into haemoglobin.
Company: bluebird bio (USA - MA)
Disease: sickle cell disease - beta-thalassemia major
- • On October 5, 2018, bluebird bio announced that the European Medicines Agency (EMA) accepted the company’s marketing authorization application (MAA) for LentiGlobin™ gene therapy for the treatment of adolescents and adults with transfusion-dependent Beta-thalassemia (TDT) and a non-Beta0/Beta0 genotype. LentiGlobin™ was previously granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the EMA in July 2018, potentially reducing the EMA’s active review time of the MAA from 210 days to 150 days.
- The MAA for LentiGlobin is supported by data from the completed Phase 1/2 Northstar (HGB-204) study and the ongoing Phase 1/2 HGB-205 study as well as available data from the Phase 3 Northstar-2 (HGB-207) study and the long-term follow-up study LTF-303.
• On July 26, 2018, bluebird bio announced that its investigational LentiGlobin™ gene therapy for the treatment of adolescent and adult patients with transfusion-dependent ?-thalassemia (TDT) and a non-Beta0/Beta0 genotype, was granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), for its upcoming marketing authorization application (MAA).
- bluebird bio intends to file an MAA for LentiGlobin in TDT with the EMA in 2018. The accelerated assessment for LentiGlobin is supported by data from clinical studies, including the completed Phase 1/2 Northstar (HGB-204) study, the ongoing Phase 1/2 HGB-205 study as well as available data from the Phase 3 Northstar-2 (HGB-207) study and the long-term follow-up study LTF-303.
- • On September 21, 2016, bluebird bio announced that the European Medicines Agency (EMA) has granted access to its Priority Medicines (PRIME) scheme for LentiGlobin drug product in the treatment of patients with transfusion-dependent beta-thalassemia. The PRIME initiative provides enhanced support and increased interaction to companies, with the goal of optimizing development plans and speeding regulatory evaluations to potentially bring innovative medicines to patients more quickly. To be accepted for PRIME, a therapy must demonstrate potential to benefit patients with unmet medical need through early clinical data or nonclinical data. Access to the PRIME initiative complements bluebird’s ongoing participation in the EMA’s Adaptive Pathways Pilot program, which also aims to expedite patient access to therapies with the potential to treat serious conditions with unmet need. It uses the existing EU regulatory framework for medicines, including conditional approval.
- Bluebird bio has recently completed enrollment in the Northstar (HGB-204) global clinical study of LentiGlobin drug product in patients with transfusion-dependent beta-thalassemia. This study, along with the supporting HGB-205 study, will form the basis of an eventual application for conditional approval in the EU under the Adaptive Pathways Pilot program.
- • On May 19, 2015, bluebird bio announced that it has met with regulatory authorities in Europe and the United States to discuss potential approval pathways for its LentiGlobin BB305 product candidate for the treatment of beta-thalassemia major. These discussions have resulted in general agreement from both agencies regarding bluebird bio’s development plans, which could potentially result in accelerated approvals.
- EMA Registration Strategy: Participate in Adaptive Pathways Pilot Program: bluebird bio is one of the first companies to participate in the European Medicines Agency’s (EMA) Adaptive Pathways (formerly referred to as Adaptive Licensing) pilot program, which is part of the EMA’s efforts to improve timely access for patients to new medicines. Based on several discussions involving the EMA, European Health Technology Assessment (HTA) agencies and patient advocacy organizations as part of this program, bluebird bio believes it is possible to seek conditional approval for the treatment of adults and adolescents with beta-thalassemia major on the basis of the totality of clinical data, in particular reduction in transfusion need, from the ongoing Northstar Study and supportive HGB-205 study. Conversion to full approval will be subject to the successful completion of the HGB-207 and HGB-208 clinical trials discussed below, supportive long-term follow-up data and “real-life” post-approval monitoring data.
- FDA Registration Strategy: Pursue Accelerated Approval Based on HGB-207 (n=15) and HGB-208 (n=15): In addition, bluebird bio has reached general agreement with the FDA on the design of its planned clinical trials HGB-207 and HGB-208. Based on its discussions with the FDA, bluebird bio believes that data from these trials, together with data from the ongoing beta-thalassemia major clinical studies (Northstar and HGB-205), could form the basis for a Biologics License Application (BLA) submission for LentiGlobin BB305. HGB-207 and HGB-208 share similar trial designs and are differentiated primarily by patient age. HGB-207 will enroll adult and adolescent patients; HGB-208 will enroll pediatric patients.
- bluebird bio has also reached general agreement with the FDA on sample size (15 patients per trial), duration (24 months of follow-up per patient) and primary endpoint (12 months of transfusion independence). In the United States, if the LentiGlobin BB305 product candidate demonstrates acceptable efficacy and safety in these patient populations, these planned clinical trials could support an accelerated approval, with post-approval confirmatory evidence to be provided with longer-term follow-up of these trials. As a result of this regulatory feedback and as required of all gene therapy clinical trials, bluebird bio has filed both clinical study protocols with the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC). The RAC has notified bluebird bio that HGB-207 does not require an in-depth review or public RAC discussion. The RAC has also notified bluebird bio that the HGB-208 study protocol is scheduled for public review on June 9, 2015.
- • On 11-12 March 2014 the Committee for Orphan Medicinal Products (COMP) has recommended the granting of an orphan designation for autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human beta A-T87Q-globin gene for treatment of sickle cell disease.
- • On February 26, 2014, the FDA has granted orphan drug designation for autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human BA-T87Q-globin gene for the treatment of sickle cell disease.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2014-02-26
Orphan status UE: 2014-04-29
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
- • On December 15, 2016, bluebird bio and apceth Biopharma announced that they have entered into a strategic manufacturing agreement providing for the future European commercial production of bluebird bio’s Lenti-D™ product candidate for cerebral adrenoleukodystropy and its LentiGlobin™ product candidate for transfusion-dependent ?-thalassemia.
- This agreement follows a successful multi-year manufacturing relationship and provides bluebird bio with European commercial manufacturing capabilities, including dedicated production suites within apceth Biopharma’s state-of-the-art GMP facility.
- Under this multi-year agreement, apceth Biopharma will perform clinical manufacturing, process validation activities and commercial manufacturing for LentiGlobin and Lenti-D drug product to support the treatment of European patients with transfusion-dependent beta thalassemia and cerebral adrenoleukodystrophy, respectively.