CAMBRIDGE, Mass.–(BUSINESS WIRE)–bluebird bio, Inc. (Nasdaq: BLUE) introduced right now that primarily based on the analyses accomplished up to now, it is vitally unlikely the Suspected Sudden Severe Opposed Response (SUSAR) of acute myeloid leukemia (AML) reported in its Part 1/2 (HGB-206) research of LentiGlobin gene remedy for sickle cell illness (SCD) (bb1111) was associated to the BB305 lentiviral vector (LVV).
“Along with our earlier findings of a number of well-known genetic mutations and gross chromosomal abnormalities generally noticed in AML on this affected person, our newest analyses recognized the combination web site for the vector inside a gene known as VAMP4. VAMP4 has no recognized affiliation with the event of AML nor with processes equivalent to mobile proliferation or genome stability. Furthermore, we see no important gene misregulation attributable to the insertion occasion,” mentioned Philip Gregory, chief scientific officer, bluebird bio. “In totality, the info from our assessments present vital proof demonstrating that it is vitally unlikely our BB305 lentiviral vector performed a job on this case and we’ve shared with the FDA that we consider these outcomes assist lifting the scientific holds on our β-thalassemia and sickle cell illness packages.”
As reported by bluebird bio on February 25, 2021, laboratory analyses confirmed that this affected person had important chromosomal abnormalities and mutations in genes usually related to the event of AML. Particularly, mutations within the RUNX1 and PTPN11 genes have been detected within the leukemic cells of this affected person. Preliminary findings urged that the BB305 LVV vector was current within the AML blast cells, however there was not ample data to find out causality.
Since then, and with the recommendation of a number of unbiased main tutorial specialists in lentiviral vector gene remedy, bluebird bio has carried out extra scientific assessments to find out the place within the genome the LVV insertion occurred, and if this integration was answerable for any change in gene regulation or gene expression close by.
A number of unbiased analyses have confirmed that vector insertion within the AML cells from this affected person came about within the VAMP4 gene, or vesicle-associated membrane protein four. VAMP4 itself has no recognized position within the improvement of AML or with any mobile course of associated to most cancers.
bluebird bio additionally assessed if there was any disruption to regular gene regulation or gene expression in and across the web site of vector insertion. Primarily based on accomplished analyses, the insertion into the VAMP4 gene has had no affect on gene expression or gene regulation nor induced any disruption of close by genes.
Primarily based on the out there outcomes up to now, bluebird bio believes that the case of AML may be very unlikely associated to the BB305 LVV. Given this, the corporate has initiated engagement with regulators to start the method of resuming scientific research for sickle cell illness and β-thalassemia.
A second SUSAR of myelodysplastic syndrome (MDS) in a affected person from Group C of HGB-206 was reported in early February and is at present being investigated to find out if the scientific findings meet the standards to be labeled as a case of MDS and, in that case, if LentiGlobin for SCD had any position. The MDS analysis was primarily based on extended anemia following LentiGlobin for SCD infusion coupled with the commentary of trisomy eight in a small share of the affected person’s bone marrow cells. Nevertheless, no blasts or dysplastic cells have been seen in an examination of the affected person’s bone marrow, and whereas trisomy eight is related to myeloid malignancies, this discovering just isn’t ample for a analysis of MDS within the absence of blasts or dysplastic cells.
The U.S. Meals and Drug Administration (FDA) has positioned a scientific maintain on the HGB-206 and HGB-210 research of LentiGlobin for SCD and the HGB-207 and HGB-212 research of betibeglogene autotemcel for β-thalassemia. The corporate is in dialogue with the FDA so as to resume all scientific research at present on scientific maintain.
An Article 20 referral process was triggered by the European Fee (EC) and shall be carried out by the European Medicines Company (EMA). The EMA’s Pharmacovigilance Danger Evaluation Committee (PRAC) will start the method of reviewing the profit/danger of ZYNTEGLO™ (betibeglogene autotemcel) for the therapy of transfusion-dependent β-thalassemia, throughout its March eight – 11 session. The committee will decide whether or not any extra pharmacovigilance measures are needed. The EMA has paused the renewal process for ZYNTEGLO’s conditional advertising authorization (CMA) whereas the PRAC evaluate is ongoing.
No instances of hematologic malignancy have been reported in any affected person who has acquired therapy with betibeglogene autotemcel for transfusion-dependent β-thalassemia, nonetheless as a result of additionally it is manufactured utilizing the identical BB305 LVV utilized in LentiGlobin for SCD, the corporate determined to quickly droop advertising of ZYNTEGLO whereas the AML case is assessed.
Investor Convention Name Info
bluebird bio will maintain a convention name to debate this replace on Wednesday, March 10 at eight:00 a.m. ET. Traders might take heed to the decision by dialing (844) 825-4408 from places in the US or +1 (315) 625-3227 from exterior the US. Please check with convention ID quantity 4148389.
To entry the stay webcast of bluebird bio’s presentation, please go to the “Occasions & Displays” web page throughout the Traders & Media part of the bluebird bio web site at http://investor.bluebirdbio.com. A replay of the webcast shall be out there on the bluebird bio web site for 90 days following the occasion.
About HGB-206 and HGB-210
HGB-206 is a Part 1/2 open-label research designed to guage the efficacy and security of LentiGlobin gene remedy for sickle cell illness (SCD) that features three therapy cohorts: Teams A, B and C. A refined manufacturing course of designed to extend vector copy quantity (VCN) and additional protocol refinements made to enhance engraftment potential of gene-modified stem cells have been used for Group C. Group C sufferers additionally acquired LentiGlobin for SCD constituted of HSCs collected from peripheral blood after mobilization with plerixafor, somewhat than through bone marrow harvest, which was utilized in Teams A and B of HGB-206.
HGB-210 is a Part Three single-arm open-label research designed to guage the efficacy and security of LentiGlobin gene remedy for SCD in sufferers between two years and 50 years of age with sickle cell illness.
About LentiGlobin for SCD (bb1111)
LentiGlobin gene remedy for sickle cell illness (bb1111) is an investigational therapy being studied as a possible therapy for SCD. bluebird bio’s scientific improvement program for LentiGlobin for SCD consists of the finished Part 1/2 HGB-205 research, the Part 1/2 HGB-206 research, and the Part Three HGB-210 research.
The U.S. Meals and Drug Administration granted orphan drug designation, quick monitor designation, regenerative drugs superior remedy (RMAT) designation and uncommon pediatric illness designation for LentiGlobin for SCD.
LentiGlobin for SCD acquired orphan medicinal product designation from the European Fee for the therapy of SCD, and Precedence Medicines (PRIME) eligibility by the EMA in September 2020.
bluebird bio is conducting a long-term security and efficacy follow-up research (LTF-307) for individuals who have participated in bluebird bio-sponsored scientific research of LentiGlobin for SCD. For extra data go to: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.
LentiGlobin for SCD is investigational and has not been permitted in any geography.
About ZYNTEGLO (betibeglogene autotemcel)
Betibeglogene autotemcel (beti-cel) is a one-time gene remedy that provides useful copies of a modified type of the β-globin gene (βA-T87Q-globin gene) right into a affected person’s personal hematopoietic (blood) stem cells (HSCs). As soon as a affected person has the βA-T87Q-globin gene, they’ve the potential to supply HbAT87Q, which is gene therapy-derived grownup Hb, at ranges which will remove or considerably scale back the necessity for transfusions. In research of beti-cel, transfusion independence (TI) is outlined as not needing crimson blood cell transfusions for a minimum of 12 months whereas sustaining a weighted common Hb of a minimum of 9 g/dL.
The European Fee granted conditional advertising authorization (CMA) for beti-cel, marketed as ZYNTEGLO™ gene remedy, for sufferers 12 years and older with transfusion-dependent β-thalassemia (TDT) who would not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is acceptable, however a human leukocyte antigen (HLA)-matched associated HSC donor just isn’t out there.
Non-serious adversarial occasions (AEs) noticed throughout scientific research that have been attributed to beti-cel included belly ache, thrombocytopenia, leukopenia, neutropenia, sizzling flush, dyspnea, ache in extremity, tachycardia and non-cardiac chest ache. One severe adversarial occasion (SAE) of thrombocytopenia was thought of probably associated to beti-cel.
Extra AEs noticed in scientific research have been according to the recognized unintended effects of HSC assortment and bone marrow ablation with busulfan, together with SAEs of veno-occlusive illness.
For particulars, please see the Abstract of Product Traits (SmPC).
On April 28, 2020, the EMA renewed the CMA for beti-cel. The CMA for beti-cel is legitimate within the 27 member states of the EU in addition to the UK, Iceland, Liechtenstein and Norway. In November 2020, bluebird bio submitted to the EMA an utility for renewal of the CMA; this process is at present on maintain. The CMA is legitimate whereas the renewal utility evaluate is ongoing and whereas it’s on maintain.
The U.S. Meals and Drug Administration granted beti-cel Orphan Drug standing and Breakthrough Remedy designation for the therapy of TDT. Beti-cel just isn’t permitted within the U.S. Beti-cel continues to be evaluated within the ongoing Part Three Northstar-2 (HGB-207) and Northstar-Three (HGB-212) research.
bluebird bio is conducting a long-term security and efficacy follow-up research, LTF-303 for individuals who have participated in bluebird bio-sponsored scientific research of ZYNTEGLO.
About bluebird bio, Inc.
bluebird bio is pioneering gene remedy with function. From our Cambridge, Mass., headquarters, we’re growing gene and cell therapies for extreme genetic illnesses and most cancers, with the aim that individuals dealing with doubtlessly deadly situations with restricted therapy choices can stay their lives totally. Past our labs, we’re working to positively disrupt the healthcare system to create entry, transparency and training in order that gene remedy can turn out to be out there to all those that can profit.
bluebird bio is a human firm powered by human tales. We’re placing our care and experience to work throughout a spectrum of issues: cerebral adrenoleukodystrophy, sickle cell illness, β-thalassemia and a number of myeloma, utilizing gene and cell remedy applied sciences together with gene addition, and (megaTAL-enabled) gene enhancing.
bluebird bio has extra nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For extra data, go to bluebirdbio.com.
Observe bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.
ZYNTEGLO, betibeglogene autotemcel, beti-cel, and bluebird bio are emblems of bluebird bio, Inc.
This launch incorporates “forward-looking statements” throughout the that means of the Non-public Securities Litigation Reform Act of 1995, together with statements concerning the Firm’s timing and expectations concerning its investigation of the connection of the AML and MDS occasions to the usage of lentiviral vector BB305 in LentiGlobin gene remedy for SCD. Any forward-looking statements are primarily based on administration’s present expectations of future occasions and are topic to plenty of dangers and uncertainties that might trigger precise outcomes to vary materially and adversely from these set forth in or implied by such forward-looking statements, a lot of that are past the Firm’s management. These dangers and uncertainties embrace, however usually are not restricted to: the danger that the Firm might not be capable of definitively decide whether or not the lentiviral vector BB305 utilized in LentiGlobin gene remedy for SCD and in betibeglogene autotemcel is said to the security occasions in a well timed method, or in any respect; the danger that the lentiviral vector BB305 has induced insertional oncogenic occasions, together with AML; the danger that insertional oncogenic occasions related to lentiviral vector or extra MDS occasions related to myeloablation shall be found or reported over time; the danger that regulatory authorities might impose a scientific maintain on extra packages; the danger that we might not be capable of deal with regulatory authorities’ considerations rapidly or in any respect; the danger that we might not resume affected person therapy with ZYNTEGLO within the business context in a well timed method or in any respect; the danger that our lentiviral vector platform throughout our extreme genetic illness packages could also be implicated, affecting the event and potential approval of elivaldogene autotemcel; the danger that we might not be capable of execute on our enterprise plans, together with our commercialization plans, assembly our anticipated or deliberate regulatory milestones, submissions, and timelines, analysis and scientific improvement plans, and in bringing our product candidates to market; and the danger that with the affect on the execution and timing of our enterprise plans, we might not efficiently execute our beforehand introduced plans to spin off our oncology packages into an unbiased publicly-traded entity. For a dialogue of different dangers and uncertainties, and different vital components, any of which might trigger our precise outcomes to vary from these contained within the forward-looking statements, see the part entitled “Danger Components” in our most up-to-date Kind 10-Okay, in addition to discussions of potential dangers, uncertainties, and different vital components in our subsequent filings with the Securities and Alternate Fee. All data on this press launch is as of the date of the discharge, and bluebird bio undertakes no responsibility to replace this data except required by regulation.