New Knowledge from bluebird bio’s Gene Therapies for Transfusion-Dependent Beta-Thalassemia and Sickle Cell Illness Offered at sixty fourth ASH Annual Assembly

SOMERVILLE, Mass.–()–Right this moment new and up to date information from bluebird bio inc.’s (NASDAQ: BLUE) gene remedy applications in beta-thalassemia and sickle cell illness had been offered on the 64th American Society of Hematology (ASH) Annual Assembly and Exposition. The up to date information show sustained therapy impact in sufferers handled with betibeglogene autotemcel (beti-cel) and lovotibeglogene autotemcel (lovo-cel) gene therapies by means of further follow-up. Case research of two sufferers recognized with persistent anemia following lovo-cel therapy had been additionally offered. The ASH Annual Assembly is happening December 10-13, 2022, in New Orleans and just about.

In 2014, bluebird bio offered the primary information demonstrating the potential of lentiviral vector gene remedy at ASH. Right this moment, with the primary FDA permitted gene remedy for beta-thalassemia in sufferers requiring common pink blood cell transfusions, and as we put together to submit a BLA for lovo-cel for sickle cell illness, we’re extraordinarily happy to be sharing up to date information demonstrating the possibly life-changing impression of our applications,” mentioned Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “Lengthy-term outcomes offered at ASH present sturdy transfusion independence in beta-thalassemia sufferers handled with beti-cel by means of eight years of follow-up, in addition to sustained therapy impact in sufferers with sickle cell illness handled with lovo-cel. Moreover, case research from our lovo-cel medical program have enhanced the sector’s understanding of the mechanism of motion of LVV gene remedy and its impression on medical security and efficacy.”

Up to date information proceed to show sustained therapy impact and high quality of life enhancements in sufferers with beta-thalassemia who require common pink blood cell transfusions following therapy with beti-cel

Lengthy-term follow-up information offered at ASH embrace follow-up for sufferers dwelling with beta-thalassemia who require common pink blood cell (RBC) transfusions as much as 8 years post-treatment (n=3), throughout ages and genotypes.

As of July 2022, 63 sufferers acquired beti-cel throughout 4 medical research and had been adopted for a median of 52.0 (20.1–101.7) months. These embrace two Part 3 research (n=41) which led to the U.S. Meals and Drug Administration (FDA) approval of ZYNTEGLO as the primary and solely gene remedy for sufferers with beta-thalassemia who require common RBC transfusions in August 2022. In these research, 90.2% (37/41) of sufferers achieved transfusion independence (TI). Sufferers who achieved TI produced regular or close to regular ranges of whole hemoglobin and demonstrated enhancements in markers of iron overload and markers of ineffective erythropoiesis.

Sufferers who achieved TI additionally confirmed continued enchancment in quality-of-life measures by means of 3 years following therapy in long-term comply with up research, LTF-303. Based mostly on affected person testimonials collected at Month 36, the power to hunt employment or be employed elevated to 93% of sufferers (13/14) from 67% (10/15) at baseline. There was additionally a discount at school absences in contrast with baseline (from 95% [18/19] of impacted sufferers to 50% [5/10]). As well as, 81% (17/21) reported enchancment in bodily exercise at three years, and 100% (20/20) reported an total profit from present process therapy with beti-cel.

No hematologic malignancies, insertional oncogenesis, vector-derived replication competent lentivirus, or clonal predominance was noticed and total, the protection of the beti-cel therapy routine largely mirrored the recognized unwanted effects the busulfan conditioning routine. Nineteen p.c (12/63) of sufferers skilled ≥1 adversarial occasion (AE) thought-about associated or probably associated to beti-cel; the commonest beti-cel associated AEs had been stomach ache (5/63 [8%]) and thrombocytopenia (3/63 [5%]). Veno-occlusive liver illness, noticed in 11% (7/63) of sufferers, resolved after therapy. One affected person who achieved TI required packed pink blood cell (pRBC) transfusions for acute occasions (for surgical procedure, Part 3, n=1).

The info had been offered in Poster #2348: Lengthy Time period Outcomes of 63 Sufferers with Transfusion-Dependent Beta-Thalassemia (TDT) Adopted As much as 8 Years Put up-Therapy with betibeglogene autotemcel (beti-cel) Gene Remedy and Exploratory Evaluation of Predictors of Profitable Therapy Outcomes in Part 3 Trials, and Poster #3665: Lengthy-Time period Affected person-Reported Outcomes Following Therapy with Betibeglogene Autotemcel in Sufferers with Transfusion-Dependent Beta-Thalassemia.

New analyses deepen understanding of security profile for lovo-cel gene remedy in sickle cell illness

Case research offered at ASH offered element on investigations into two circumstances of persistent anemia noticed in an grownup and pediatric affected person in Group C, the pivotal cohort of the HGB-206 research of lovo-cel; information had been as of August 2022.

Each sufferers had two α-globin gene deletions (−α3.7/−α3.7), also called alpha-thalassemia trait, and notably are the one sufferers within the research with this particular genotype. Integration website evaluation and next-generation sequencing confirmed no proof of clonal processes (vector-related or in any other case) and findings usually are not in line with an rising hematologic malignancy. Medical investigations offered recommend that the alpha-thalassemia trait seemingly contributed to anemia after lovo-cel infusion. Following these circumstances, this genotype was added to exclusion standards for ongoing research.

An in-depth evaluation of two circumstances of ineffective erythropoiesis with persistent anemia following lovo-cel therapy reassure that these circumstances would not have clonal evolution or an rising malignancy. The working speculation is that the anemia is attributable to alpha-thalassemia trait with sturdy HbAT87Q manufacturing,” mentioned Mark C. Walters, M.D., Jordan Household Director, BMT Program, UCSF Benioff Kids’s Hospital Oakland, Oakland, CA.

Up to date information from the HGB-206 guardian research offered at ASH confirmed 96% (31/32) of sufferers handled in Group C skilled full decision of extreme vaso-occlusive occasions (sVOE) by means of 24 months of follow-up; a single sVOE was noticed within the grownup affected person experiencing persistent anemia. As of final follow-up of 24 months, the grownup affected person is transfusion dependent and experiencing intermittent exacerbations of persistent ache, whereas the pediatric affected person has not required transfusions and stays clinically properly.

In Group C of HGB-206, the protection profile of the lovo-cel therapy routine from Day 1 to Month 24 usually displays the recognized unwanted effects of busulfan conditioning routine, and AEs generally seen within the inhabitants being evaluated. Probably the most ceaselessly reported critical AEs after lovo-cel infusion in two or extra HGB-206 Group C sufferers had been ache (11.1%), stomach ache, anemia, drug withdrawal syndrome (opiate), nausea, suicidal ideation, and vomiting (5.6% every). There have been no circumstances of veno-occlusive liver illness, graft failure, insertional oncogenesis or replication-competent lentivirus.

The info had been offered in Oral #11: lovo-cel (bb1111) Gene Remedy for Sickle Cell Illness: Up to date Medical Outcomes and Investigations into Two Circumstances of Anemia from Group C of the Part 1/2 HGB-206 Research​.

Research evaluating lovo-cel in sickle cell illness symbolize probably the most mature sickle cell illness gene remedy dataset within the {industry}, with the longest accessible follow-up information. As of August 2022, 50 sufferers have been handled with lovo-cel throughout the HGB-205 (n=3), HGB-206 (n=45) and HGB-210 (n=2) medical research, with as much as 7 years of affected person follow-up (median: 37.7 months) representing 176.5 whole patient-years of knowledge.

bluebird bio stays on observe to submit a biologics license software (BLA) for lovo-cel in Q1 2023.

About ZYNTEGLO® (betibeglogene autotemcel) or beti-cel

ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene remedy permitted for the therapy of beta-thalassemia in grownup and pediatric sufferers who require common pink blood cell transfusions. ZYNTEGLO works by including purposeful copies of a modified type of the beta-globin gene (βA-T87Q-globin gene) right into a affected person’s personal hematopoietic (blood) stem cells to allow the manufacturing of a modified purposeful grownup hemoglobin (HbAT87Q). As soon as a affected person has the βA-T87Q-globin gene, they’ve the potential to extend ZYNTEGLO-derived grownup hemoglobin (HbAT87Q) and whole hemoglobin to regular or close to regular ranges that may eradicate the necessity for normal pink blood cell (RBC) transfusions.


ZYNTEGLO is indicated for the therapy of grownup and pediatric sufferers with beta-thalassemia who require common pink blood cell (RBC) transfusions.

Necessary Security Data

Delayed Platelet Engraftment

Delayed platelet engraftment has been noticed with ZYNTEGLO therapy. Bleeding danger is elevated previous to platelet engraftment and will proceed after engraftment in sufferers with extended thrombocytopenia; 15% of sufferers had ≥ Grade 3 decreased platelets on or after Day 100.

Sufferers ought to be made conscious of the chance of bleeding till platelet restoration has been achieved. Monitor sufferers for thrombocytopenia and bleeding in response to customary pointers. Conduct frequent platelet counts till platelet engraftment and platelet restoration are achieved. Carry out blood cell depend dedication and different acceptable testing every time medical signs suggestive of bleeding come up.

Threat of Neutrophil Engraftment Failure

There’s a potential danger of neutrophil engraftment failure after therapy with ZYNTEGLO. Neutrophil engraftment failure is outlined as failure to realize three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on totally different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts till engraftment has been achieved. If neutrophil engraftment failure happens in a affected person handled with ZYNTEGLO, present rescue therapy with the back-up assortment of CD34+ cells.

Threat of Insertional Oncogenesis

There’s a potential danger of LVV mediated insertional oncogenesis after therapy with ZYNTEGLO.

Sufferers handled with ZYNTEGLO could develop hematologic malignancies and ought to be monitored lifelong. Monitor for hematologic malignancies with a whole blood depend (with differential) at Month 6 and Month 12 after which a minimum of yearly for a minimum of 15 years after therapy with ZYNTEGLO, and integration website evaluation at Months 6, 12, and as warranted.

Within the occasion {that a} malignancy happens, contact bluebird bio at 1 833-999-6378 for reporting and to acquire directions on assortment of samples for testing.

Hypersensitivity Reactions

Allergic reactions could happen with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO could trigger hypersensitivity reactions, together with anaphylaxis.

Anti-retroviral and Hydroxyurea Use

Sufferers mustn’t take prophylactic HIV anti-retroviral drugs or hydroxyurea for a minimum of one month previous to mobilization, or for the anticipated length for elimination of the drugs, and till all cycles of apheresis are accomplished. If a affected person requires anti-retrovirals for HIV prophylaxis, then verify a detrimental take a look at for HIV earlier than starting mobilization and apheresis of CD34+ cells.

Interference with Serology Testing

Sufferers who’ve acquired ZYNTEGLO are more likely to take a look at optimistic by polymerase chain response (PCR) assays for HIV on account of built-in BB305 LVV proviral DNA, leading to a false-positive take a look at for HIV. Due to this fact, sufferers who’ve acquired ZYNTEGLO shouldn’t be screened for HIV an infection utilizing a PCR‑primarily based assay.

Hostile Reactions

The most typical non-laboratory adversarial reactions (≥20%) had been mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, stomach ache, musculoskeletal ache, cough, headache, diarrhea, rash, constipation, nausea, decreased urge for food, pigmentation dysfunction, and pruritus. The most typical Grade 3 or 4 laboratory abnormalities (>50%) embrace neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

Drug Interactions

Drug-drug interactions between iron chelators and the myeloablative conditioning agent have to be thought-about. Iron chelators ought to be discontinued a minimum of 7 days previous to initiation of conditioning. The prescribing data for the iron chelator(s) and the myeloablative conditioning agent ought to be consulted for the suggestions concerning co-administration with CYP3A substrates.

Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, keep away from use of those iron chelators for six months. If iron chelation is required, take into account administration of non-myelosuppressive iron chelators. Phlebotomy can be utilized in lieu of iron chelation, when acceptable.

Being pregnant/Lactation

Advise sufferers of the dangers related to conditioning brokers, together with on being pregnant and fertility.

ZYNTEGLO shouldn’t be administered to ladies who’re pregnant, and being pregnant after ZYNTEGLO infusion ought to be mentioned with the treating doctor.

ZYNTEGLO just isn’t advisable for girls who’re breastfeeding, and breastfeeding after ZYNTEGLO infusion ought to be mentioned with the treating doctor.

Females and Males of Reproductive Potential

A detrimental serum being pregnant take a look at have to be confirmed previous to the beginning of mobilization and re-confirmed previous to conditioning procedures and earlier than ZYNTEGLO administration.

Girls of childbearing potential and males able to fathering a baby ought to use an efficient technique of contraception (intra uterine gadget or mixture of hormonal and barrier contraception) from begin of mobilization by means of a minimum of 6 months after administration of ZYNTEGLO.

Advise sufferers of the choice to cryopreserve semen or ova earlier than therapy if acceptable.

Please see full Prescribing Data for ZYNTEGLO.

About lovotibeglogene autotemcel (lovo-cel; previously bb1111)

lovotibeglogene autotemcel (lovo-cel) gene remedy is an investigational one-time therapy being studied for sickle cell illness (SCD), that’s designed so as to add purposeful 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 sufferers have the βA-T87Q-globin gene, their pink blood cells (RBCs) can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the objective of lowering sickled RBCs, hemolysis, and different issues. bluebird bio’s medical improvement program for lovo-cel contains the finished Part 1/2 HGB-205 and ongoing Part 1/2 HGB-206 and Part 3 HGB-210 research. bluebird bio can be conducting a long-term security and efficacy follow-up research (LTF-307) for individuals who have participated in bluebird bio sponsored medical research of lovo-cel.

The lovo-cel medical program is at present on a partial medical maintain associated to an adolescent affected person with persistent, non-transfusion-dependent anemia. The Firm stays in energetic communication with the FDA to resolve the partial medical maintain and resume enrollment and therapy of sufferers beneath the age of 18.

About bluebird bio, Inc.

bluebird bio is pursuing healing gene therapies to present sufferers and their households extra bluebird days.

With a devoted concentrate on extreme genetic illnesses, bluebird has industry-leading applications for sickle cell illness, β-thalassemia and cerebral adrenoleukodystrophy and is advancing analysis to use new applied sciences to those and different illnesses. We customized design every of our therapies to deal with the underlying reason behind illness and have developed in-depth and efficient analytical strategies to grasp the protection of our lentiviral vector applied sciences and drive the sector of gene remedy ahead.

Based in 2010, bluebird has the biggest and deepest ex-vivo gene remedy information set on this planet—setting the usual for the {industry}. Right this moment, bluebird continues to forge new paths, combining our real-world expertise with a deep dedication to affected person communities and a people-centric tradition that pulls and grows a various flock of devoted birds.

For extra data, go to or comply with us on social media at @bluebirdbio, LinkedIn, Instagram and YouTube.

ZYNTEGLO and bluebird bio are logos of bluebird bio, Inc.

bluebird bio Cautionary Assertion Concerning Ahead-Wanting Statements

This press launch incorporates “forward-looking statements” inside the which means of the Personal Securities Litigation Reform Act of 1995. All statements that aren’t statements of historic information are, or could also be deemed to be, forward-looking statements, together with our statements concerning the timing for a possible BLA submission for lovo-cel and the potential impression of our medical trial information and findings. Such forward-looking statements are primarily based on historic efficiency and present expectations and projections about our future monetary outcomes, objectives, plans and goals and contain inherent dangers, assumptions and uncertainties, together with inside or exterior elements that might delay, divert or change any of them within the subsequent a number of years, which might be tough to foretell, could also be past our management and will trigger our future monetary outcomes, objectives, plans and goals to vary materially from these expressed in, or implied by, the statements. No forward-looking assertion may be assured. Ahead-looking statements on this press launch ought to be evaluated along with the various dangers and uncertainties that have an effect on bluebird bio’s enterprise, significantly these recognized within the danger elements dialogue in bluebird bio’s Annual Report on Kind 10-Okay, as up to date by our subsequent Quarterly Reviews on Kind 10-Q, Present Reviews on Kind 8-Okay and different filings with the Securities and Alternate Fee. These dangers embrace, however usually are not restricted to: the chance that we could not understand anticipated value financial savings from the restructuring, together with the anticipated lower in operational bills, on the ranges we count on; we could encounter further delays within the improvement of our applications, together with the imposition of latest medical holds or delays in resolving current medical holds, that will impression our capability to fulfill our anticipated timelines and improve our prices; the inner and exterior prices required for our ongoing and deliberate actions, and the ensuing impression on expense and use of money, could also be increased than anticipated which can trigger us to make use of money extra rapidly than we count on or change or curtail a few of our plans or each; our expectations as to bills, money utilization and money wants could show to not be appropriate for different causes comparable to modifications in plans or precise occasions being totally different than our assumptions; the chance that the efficacy and security outcomes from our prior and ongoing medical trials is not going to proceed or be seen in further sufferers handled with our product candidates; the chance that further insertional oncogenic or different reportable occasions related to lentiviral vector, drug product, or myeloablation might be found or reported over time; the chance that our eli-cel, beti-cel and lovo-cel applications could also be topic to additional delays of their improvement, together with however not restricted to the imposition of latest medical holds; the chance that lovo-cel might not be permitted inside the precedence evaluate timeframe or in any respect; and the chance that anybody or extra of our merchandise and product candidates, together with eli-cel, beti-cel or lovo-cel, is not going to be efficiently developed, permitted or commercialized. The forward-looking statements included on this doc are made solely as of the date of this doc and besides as in any other case required by relevant legislation, bluebird bio undertakes no obligation to publicly replace or revise any forward-looking assertion, whether or not on account of new data, future occasions, modified circumstances or in any other case.


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